Evaluate Azithromycin Plus Chloroquine And Sulfadoxine Plus Pyrimethamine Combinations For Intermittent Preventive Treatment Of Falciparum Malaria Infection In Pregnant Women In Africa

• Sponsor: Pfizer (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01103063
• Collaborator: London School of Hygiene and Tropical Medicine (Other), Medicines for Malaria Venture (Other)
• Enrollment: 2,891
• Locations: 9
• Arms: 2
• Duration (Months): 37
• Patients Per Site: 321.2
• Patients Per Site Per Month: 8.7

Study Details

Study Description

Brief Summary

The primary objective is to establish superiority of AZCQ over SP in protective efficacy for IPTp as measured by the proportion of subjects with sub-optimal pregnancy outcome.

Condition or Disease	Intervention/Treatment	Phase
Intermittent Preventive Treatment In Pregnancy (IPTp)	Drug: Azithromycin plus chloroquine; Drug: sulfadoxine-pyrimethamine	Phase 3

Detailed Description

After interim analysis of efficacy data by an External Data Monitoring Committee, this study was terminated. Investigators were notified on 22 Aug 2013. There were no safety concerns that led to this termination.

Study Design

• Study Type: Interventional
• Actual Enrollment: 2891 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: A Phase 3, Open Label, Randomized, Comparative Study To Evaluate Azithromycin Plus Chloroquine And Sulfadoxine Plus Pyrimethamine Combinations For Intermittent Preventive Treatment Of Falciparum Malaria Infection In Pregnant Women In Africa
• Study Start Date: Oct 1, 2010
• Actual Primary Completion Date: Oct 1, 2013
• Actual Study Completion Date: Nov 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AZCQ Azithromycin/chloroquine	Drug: Azithromycin plus chloroquine; combination tablet of 250mg azithromycin/155 chloroquine, Once daily PO for three days per treatment. There are total 3 treatments at 4-8 weeks intervals. The first treatment course will be administered during the second trimester (14-26 weeks of gestation as confirmed by ultrasound). The last treatment course should be given to subjects prior to or during 36 weeks of gestation.
Active Comparator: SP sulfadoxine-pyrimethamine (Fansidar)	Drug: sulfadoxine-pyrimethamine; Fansidar tablet (500 mg sulfadoxine /25 mg pyrimethamine), once daily, PO, single dose per treatment. There are total 3 treatments at 4-8 weeks intervals. The first treatment course will be administered during the second trimester (14-26 weeks of gestation as confirmed by ultrasound). The last treatment course should be given to subjects prior to or during 36 weeks of gestation.; Other Names: Fansidar

Outcome Measures

Primary Outcome Measures

1. Percentage Participants With Sub-optimal Pregnancy Outcome in Intent-to-Treat (IIT) Population [Approximately 40 weeks of gestational age]

   Adverse pregnancy outcomes were defined as live-borne neonate (singleton) with low birth weight (LBW) (<2,500 g), premature births (<37 weeks as confirmed by the Ballard score), abortion (≤28 weeks), still birth (>28 weeks), lost to follow-up prior to termination of pregnancy or delivery, or missing birth weight of the neonates.

Secondary Outcome Measures

1. Percentage of Participants With Sub-optimal Pregnancy Outcome in Efficacy Analyzable Per Protocol (PP) Population [Approximately 40 weeks of gestational age]

   Adverse pregnancy outcomes were defined as live-borne neonate (singleton) with LBW (<2,500g), premature births (<37 weeks as confirmed by the Ballard score), abortion (≤28 weeks), still birth (>28 weeks), lost to follow-up prior to termination of pregnancy or delivery, or missing birth weight of the neonates.

2. Percentage of Neonates With LBW (<2500 g) in ITT Population [Approximately 40 weeks of gestational age]

   LBW was defined as live birth weight <2500 g (up to and including 2499 g).

3. Percentage of Neonates With LBW (<2500 g) in Efficacy Analyzable PP Population [Approximately 40 weeks of gestational age]

   LBW was defined as live birth weight <2500 g (up to and including 2499 g).

4. Percentage of Participants With Severe Maternal Anemia (Hemoglobin [Hb] <8 g/dL) at 36-38 Weeks of Gestation [At 36-38 weeks of gestation.]

   Severe maternal anemia was defined as Hb <8 g/dL.

5. Percentage of Participants With Maternal Anemia (Hb <11 g/dL) at 36-38 Weeks of Gestation [At 36-38 weeks of gestation.]

   Anemia was defined as Hb <11 g/dL.

6. Percentage of Participants With Placental Parasitemia at Delivery [Approximately 40 weeks of gestational age]

   Participants with placental parasitemia at delivery were diagnosed using Placental blood smear at birth from participants who deliver at hospital.

7. Percentage of Participants With Placental Malaria at Delivery Based on Histology [Approximately 40 weeks of gestational age]

   Participants positive for placental malaria at delivery were evaluated based on placental histology.

8. Sexually Transmitted Infection (STI) Episodes Per Participant [Approximately 40 weeks of gestational age .]

   Number of episodes of sexually transmitted infection episodes per participant were noted. The STI's including Treponema pallidum, Neisseria gonorrhoeae, Chlamydia trachomatis, from first dose to delivery (diagnosis was based on clinical presentation and lab results).

9. Percentage of Participants With Sub-optimal Pregnancy Outcome Including Neonatal Death and Congenital Malformation [Approximately 40 weeks of gestational age.]

   Sub-optimal pregnancy outcome including neonatal deaths and congenital malformations, defined as any of the following: live-borne neonate (singleton) with low birth-weight (or LBW for short, defined as live birth weight <2,500g), premature birth (<37 weeks), abortion (≤28 weeks), still birth (>28 weeks), neonatal death, congenital malformation, lost to follow-up prior to termination of pregnancy or delivery, or missing birth weight of the neonates.

10. Change From Baseline to 36-38 Weeks of Gestation in Hb Concentration. [Baseline, at 36-38 weeks of gestation.]

    Change from Baseline to 36-38 weeks of gestation in Hb concentration was noted.

11. Percentage of Neonates With Congenital Abnormalities at Birth [Approximately 40 weeks of gestational age.]

    Neonates with congenital abnormalities at birth were noted.

12. Percentage of Perinatal or Neonatal Deaths [Day 28 after delivery.]

    Percentage of perinatal or neonatal deaths were noted.

13. Birth Weight of Live Borne Neonate [Approximately 40 weeks of gestational age.]

    Birth weight of live borne neonates were calculated in grams.

14. Number of Episodes of Symptomatic Malaria Per Participant From First Intermittent Preventive Treatment of Falciparum Dose to Delivery [Approximately 40 weeks of gestational age]

    This outcome measure determined if an episode of malaria started within the time period of first dose to delivery. Clinical episode of malaria was determined if the participant presented with clinical symptoms of malaria (fever >37.5°C, oral) and diagnosed (either by rapid diagnostic tests or microscopy) with malaria.

15. Percentage of Participants Requiring Additional Treatment for Symptomatic Malaria From First Dose to Delivery [Approximately 40 weeks of gestational age]

    This outcome measure evaluated the participants requiring additional treatments for malaria during the study period following the first dose (diagnosed based on clinical presentation and/or lab test results).

16. Percentage of Participants With Peripheral Parasitemia at 36-38 Weeks of Gestation [At 36-38 weeks of gestation]

    This outcome measure evaluated the percentage of participants positive for peripheral parasitemia at 36-38 weeks of gestation. A participant was positive for parasitemia if the number of asexual parasites per μL was >0.

17. Percentage of Participants With Peripheral Parasitemia at Delivery [Approximately 40 weeks of gestational age]

    This outcome measure evaluated the percentage of participants positive for peripheral parasitemia at delivery. A participant was positive for parasitemia if the number of asexual parasites per μL was >0.

18. Percentage of Participants With Cord Blood Parasitemia at Delivery [Approximately 40 weeks of gestational age]

    This outcome measure evaluated the percentage of participants positive for cord blood parasitemia at delivery. A participant was positive for parasitemia if the number of asexual parasites per μL was >0.

19. Percentage of Participants With Sexually Transmitted Infections From First Dose to 36-38 Weeks of Gestation [Upto 36-38 weeks of gestation]

    Sexual transmitted disease included Treponema pallidum, Neisseria gonorrhoeae, and Chlamydia trachomatis infections. This was diagnosed based on clinical presentation prior to Week 36-38 and/or lab test results between Week 36-38.

20. Percentage of Participants With Chlamydia Trachomatis Infection at 36-38 Weeks of Gestation [At 36-38 weeks of gestation]

    Participants positive for Chlamydia trachomatis infection was diagnosed based on laboratory result at 36-38 weeks of gestation. A vaginal swab was collected and PCR assay was used for analysis.

21. Percentage of Participants With Neisseria Gonorrhoeae Infection at 36-38 Weeks of Gestation [At 36-38 weeks of gestation]

    Participants positive for Neisseria gonorrhoeae infection was diagnosed based on laboratory result at 36-38 weeks of gestation. A vaginal swab was collected and PCR assay was used for analysis.

22. Percentage of Participants With Treponema Pallidum Infection at 36-38 Weeks of Gestation [At 36-38 weeks of gestation]

    Participants positive for Treponema pallidum infection was diagnosed based on laboratory result at 36-38 weeks of gestation. Treponema Pallidum particle Agglutination Assay was used.

23. Percentage of Participants With Trichomonas Vaginalis Infection at 36-38 Weeks of Gestation [At 36-38 weeks of gestation]

    Participants positive for Trichomonas vaginalis infection was diagnosed based on laboratory result at 36-38 weeks of gestation. A vaginal swab was collected for the laboratory test.

24. Percentage of Participants With Bacterial Vaginosis Infection at 36-38 Weeks of Gestation. [At 36-38 weeks of gestation]

    Bacterial vaginosis was diagnosed based on laboratory result at 36-38 weeks of gestation. A vaginal swab was collected for the Gram staining.

25. Percentage of Neonates With Ophthalmia Neonatorum at Birth Period [Approximately 40 weeks of gestational age]

    Ophthalmia neonatorum was diagnosed at birth. The laboratory diagnosis was performed among neonates with purulent discharge.

26. Percentage of Participants With Bacterial Infections Including Pneumonia and Other Lower Respiratory Tract Infections From First Dose to Delivery [Up to approximately 40 weeks of gestational age]

    Participants positive for bacterial infections including other lower respiratory tract infections were measured anytime from first dose administration to delivery.

27. Percentage of Participants With Pre-eclampsia From Week 20 to Delivery [From Week 20 to approximately 40 weeks of gestational age]

    Pre-eclampsia was diagnosed as systolic blood pressure of at least 140 mmHg and/or diastolic blood pressure of at least 90 mmHg on two separate readings taken at least 4 hours apart and proteinuria at least 300 mg protein in a 24 hour urine collection.

28. Nasopharyngeal Swabs Positive for Macrolide Resistant Streptococcus Pneumoniae [Visits 6 and 7]

    This outcome measure evaluated the Streptococcus pneumoniae sensitivity against macrolide antibiotics.

29. Nasopharyngeal Swabs Positive for Penicillin Resistant Streptococcus Pneumoniae [Visits 6 and 7]

    This outcome measure evaluated the Streptococcus pneumoniae sensitivity against penicillin antibiotics.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 16 Years to 35 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Pregnant women (all gravidae) with ≥14 and ≤26 weeks of gestational age (by ultrasound).

• Evidence of a personally signed and dated informed consent/assent document. Assent will be obtained from subjects <18 years of age.

• Subjects who are willing to and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

• Subjects who are available for follow up at delivery and on 28 days post delivery.

Exclusion Criteria:

• Age <16 years old or >35 years old.

• Multiple gestations as per the ultrasound at screening.

• Clinical symptoms of malaria.

• Hemoglobin < 8 g/dL (at enrollment).

• Any condition requiring hospitalization at enrollment.

• History of convulsions, hypertension, diabetes or any other chronic illness that may adversely affect fetal growth and viability.

• Inability to tolerate oral treatment in tablet form.

• Known allergy to the study drugs (azithromycin, chloroquine, and sulfadoxine-pyrimethamine) or to any macrolides or sulphonamides.

• Requirement to use medication during the study that might interfere with the evaluation of the study drug eg, trimethoprim-sulfamethoxazole use in subjects positive for HIV infection.

• Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation.

• Evidence of current obstetric complications that may adversely impact the pregnancy and/or fetal outcomes, including presence of congenital anomalies, placenta previa or abruption.

• Known severe Sickle Cell (SS) disease or Sickle Hemoglobin C (SC) anemia.

• Known family history of prolonged QT Syndrome, serious ventricular arrhythmia, or sudden cardiac death.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Centre de Santé d'AHOUANSORI-AGUE	Cotonou		Benin
2	Hôpital Bethesda	Cotonou		Benin
3	Siaya District Hospital	Siaya		Kenya
4	Zomba Central Hospital	Zomba		Malawi
5	Teule Hospital	Muheza	Tanga	Tanzania
6	Bugando Medical Centre	Mwanza		Tanzania	1903
7	Nyamagana District Hospital, c/o National Institute for Medical Research, Mwanza Centre	Mwanza		Tanzania
8	Nyamagana District Hospital	Mwanza		Tanzania
9	Mulago Hospital Complex	Kampala		Uganda

Sponsors and Collaborators

• Pfizer
• London School of Hygiene and Tropical Medicine
• Medicines for Malaria Venture

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT01103063
• Other Study ID Numbers: A0661158
• First Posted: Apr 13, 2010
• Last Update Posted: Jun 16, 2015
• Last Verified: May 1, 2015

• Keywords provided by Pfizer: P. falciparum malaria; IPTp
• Additional relevant MeSH terms: Malaria; Malaria, Falciparum; Azithromycin; Chloroquine; Pyrimethamine; Sulfadoxine; Fanasil, pyrimethamine drug combination

Study Results

Participant Flow

Recruitment Details	This Phase 3, open label, randomized, parallel group study screened a total of 3259 participants in 6 sites. A total of 2891 were treated either with azithromycin+chloroquine or sulfadoxine+pyrimethamine.
Pre-assignment Detail	Pregnant women (all gravidae) with ≥14 and ≤26 weeks of gestational age were to be enrolled in this study. Approximately half of the participants were to be primigravidae and secundigravidae pregnant women since they had a higher risk for suboptimal pregnancy outcomes due to malaria.

Arm/Group Title	Azithromycin + Chloroquine	Sulfadoxine + Pyrimethamine
Arm/Group Description	The participants received 1000 mg Azithromycin (AZ) and 620 mg of Chloroquine (CQ) base (4 combination tablets of AZCQ with individual strength of 250 mg/155 mg), by mouth once daily for 3 days (Days 0, 1, 2) per treatment. There were a total of 3 treatments at 4-8 week intervals.	The participants received sulfadoxine-pyrimethamine (SP) (Fansidar) treatment course: 1500 mg sulfadoxine and 75 mg pyrimethamine (3 fixed tablets of SP strength at 500 mg/25 mg), single oral dose on Day 0 of each treatment. There were a total of 3 treatments at 4-8 week intervals.
Period Title: Overall Study
STARTED	1446	1445
COMPLETED	969	1024
NOT COMPLETED	477	421

Baseline Characteristics

Arm/Group Title	Azithromycin + Chloroquine	Sulfadoxine + Pyrimethamine	Total
Arm/Group Description	The participants received 1000 mg Azithromycin (AZ) and 620 mg of Chloroquine (CQ) base (4 combination tablets of AZCQ with individual strength of 250 mg/155 mg), by mouth once daily for 3 days (Days 0, 1, 2) per treatment. There were a total of 3 treatments at 4-8 week intervals.	The participants received sulfadoxine-pyrimethamine (SP) (Fansidar) treatment course: 1500 mg sulfadoxine and 75 mg pyrimethamine (3 fixed tablets of SP strength at 500 mg/25 mg), single oral dose on Day 0 of each treatment. There were a total of 3 treatments at 4-8 week intervals.	Total of all reporting groups
Overall Participants	1446	1445	2891
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	23.3 (4.5)	23.3 (4.6)	23.3 (4.6)
Sex: Female, Male (Count of Participants)
Female	1446 100%	1445 100%	2891 100%
Male	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Percentage Participants With Sub-optimal Pregnancy Outcome in Intent-to-Treat (IIT) Population
Description	Adverse pregnancy outcomes were defined as live-borne neonate (singleton) with low birth weight (LBW) (<2,500 g), premature births (<37 weeks as confirmed by the Ballard score), abortion (≤28 weeks), still birth (>28 weeks), lost to follow-up prior to termination of pregnancy or delivery, or missing birth weight of the neonates.
Time Frame	Approximately 40 weeks of gestational age

Outcome Measure Data

Analysis Population Description

ITT set was used which consisted of participants who were randomized, received at least one dose of study medication (Day 0 at Visit 1 was considered the first dose of study medication), and who had a single fetus.

Arm/Group Title	Azithromycin + Chloroquine	Sulfadoxine + Pyrimethamine
Arm/Group Description	The participants received 1000 mg Azithromycin (AZ) and 620 mg of Chloroquine (CQ) base (4 combination tablets of AZCQ with individual strength of 250 mg/155 mg), by mouth once daily for 3 days (Days 0, 1, 2) per treatment. There were a total of 3 treatments at 4-8 week intervals.	The participants received sulfadoxine-pyrimethamine (SP) (Fansidar) treatment course: 1500 mg sulfadoxine and 75 mg pyrimethamine (3 fixed tablets of SP strength at 500 mg/25 mg), single oral dose on Day 0 of each treatment. There were a total of 3 treatments at 4-8 week intervals.
Measure Participants	1445	1445
Number (95% Confidence Interval) [Percentage of participants]	26.16 1.8%	23.67 1.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azithromycin + Chloroquine, Sulfadoxine + Pyrimethamine
	Comments	The 2-sided P-value tests the null hypothesis that the relative risk equals 1 (treatment group equality) versus not equal 1.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.12237
	Comments	Mantel-Haenszel estimate of the common relative risk is presented, adjusting for randomization strata. A relative risk less than 1 favors Azithromycin + Chloroquine treatment group (reduction in risk for the endpoint)
	Method	Mantel Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.11
	Confidence Interval	(2-Sided) 95%; 0.97 to 1.25
	Parameter Dispersion	Type: Standard Deviation; Value: 0.0647
	Estimation Comments	The estimated risk ratio is presented along with its standard error (SE), with the SE on the log(e) scale.

2. Secondary Outcome

Title	Percentage of Participants With Sub-optimal Pregnancy Outcome in Efficacy Analyzable Per Protocol (PP) Population
Description	Adverse pregnancy outcomes were defined as live-borne neonate (singleton) with LBW (<2,500g), premature births (<37 weeks as confirmed by the Ballard score), abortion (≤28 weeks), still birth (>28 weeks), lost to follow-up prior to termination of pregnancy or delivery, or missing birth weight of the neonates.
Time Frame	Approximately 40 weeks of gestational age

Outcome Measure Data

Analysis Population Description

Subset of ITT participants: outcome or withdrawal occurred on or before 8/27/2013 (date of study termination), compliant with study medication, birth weight measured on or before 7 days after birth if not already a failure, and did not switch to standard of care.

Arm/Group Title	Azithromycin + Chloroquine	Sulfadoxine + Pyrimethamine
Arm/Group Description	The participants received 1000 mg Azithromycin (AZ) and 620 mg of Chloroquine (CQ) base (4 combination tablets of AZCQ with individual strength of 250 mg/155 mg), by mouth once daily for 3 days (Days 0, 1, 2) per treatment. There were a total of 3 treatments at 4-8 week intervals.	The participants received sulfadoxine-pyrimethamine (SP) (Fansidar) treatment course: 1500 mg sulfadoxine and 75 mg pyrimethamine (3 fixed tablets of SP strength at 500 mg/25 mg), single oral dose on Day 0 of each treatment. There were a total of 3 treatments at 4-8 week intervals.
Measure Participants	1089	1176
Number (95% Confidence Interval) [Percentage of Participants]	10.38 0.7%	10.12 0.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azithromycin + Chloroquine, Sulfadoxine + Pyrimethamine
	Comments	The 2-sided P-value tests the null hypothesis that the relative risk equals 1 (treatment group equality) versus not equal 1.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.84117
	Comments	Mantel-Haenszel estimate of the common relative risk is presented, adjusting for randomization strata. A relative risk less than 1 favors Azithromycin + Chloroquine treatment group (reduction in risk for the endpoint)
	Method	Mantel Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.03
	Confidence Interval	(2-Sided) 95%; 0.80 to 1.31
	Parameter Dispersion	Type: Standard Deviation; Value: 0.1243
	Estimation Comments	The estimated risk ratio is presented along with its SE, with the SE on the log(e) scale.

3. Secondary Outcome

Title	Percentage of Neonates With LBW (<2500 g) in ITT Population
Description	LBW was defined as live birth weight <2500 g (up to and including 2499 g).
Time Frame	Approximately 40 weeks of gestational age

Outcome Measure Data

Analysis Population Description

ITT set was used which consisted of participants who were randomized, received at least one dose of study medication (Day 0 at Visit 1 was considered the first dose of study medication), and who had a single fetus. N=Total live births.

Arm/Group Title	Azithromycin + Chloroquine	Sulfadoxine + Pyrimethamine
Arm/Group Description	The participants received 1000 mg Azithromycin (AZ) and 620 mg of Chloroquine (CQ) base (4 combination tablets of AZCQ with individual strength of 250 mg/155 mg), by mouth once daily for 3 days (Days 0, 1, 2) per treatment. There were a total of 3 treatments at 4-8 week intervals.	The participants received sulfadoxine-pyrimethamine (SP) (Fansidar) treatment course: 1500 mg sulfadoxine and 75 mg pyrimethamine (3 fixed tablets of SP strength at 500 mg/25 mg), single oral dose on Day 0 of each treatment. There were a total of 3 treatments at 4-8 week intervals.
Measure Participants	1140	1190
Number (95% Confidence Interval) [Percentage of neonates]	5.01	5.72

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azithromycin + Chloroquine, Sulfadoxine + Pyrimethamine
	Comments	The 2-sided P-value tests the null hypothesis that the relative risk equals 1 (treatment group equality) versus not equal 1.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4428
	Comments	Mantel-Haenszel estimate of the common relative risk is presented, adjusting for randomization strata. A relative risk less than 1 favors Azithromycin + Chloroquine treatment group (reduction in risk for the endpoint).
	Method	Mantel Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.87
	Confidence Interval	(2-Sided) 95%; 0.62 to 1.23
	Parameter Dispersion	Type: Standard Deviation; Value: 0.1745
	Estimation Comments	The estimated risk ratio is presented along with its standard error (SE), with the SE on the log(e) scale.

4. Secondary Outcome

Title	Percentage of Neonates With LBW (<2500 g) in Efficacy Analyzable PP Population
Description	LBW was defined as live birth weight <2500 g (up to and including 2499 g).
Time Frame	Approximately 40 weeks of gestational age

Outcome Measure Data

Analysis Population Description

Subset of ITT participants: outcome or withdrawal occurred on or before 8/27/2013 (date of study termination), compliant with study medication, birth weight measured on or before 7 days after birth if not already a failure, and did not switch to standard of care. N=Total Live Births.

Arm/Group Title	Azithromycin + Chloroquine	Sulfadoxine + Pyrimethamine
Arm/Group Description	The participants received 1000 mg Azithromycin (AZ) and 620 mg of Chloroquine (CQ) base (4 combination tablets of AZCQ with individual strength of 250 mg/155 mg), by mouth once daily for 3 days (Days 0, 1, 2) per treatment. There were a total of 3 treatments at 4-8 week intervals.	The participants received sulfadoxine-pyrimethamine (SP) (Fansidar) treatment course: 1500 mg sulfadoxine and 75 mg pyrimethamine (3 fixed tablets of SP strength at 500 mg/25 mg), single oral dose on Day 0 of each treatment. There were a total of 3 treatments at 4-8 week intervals.
Measure Participants	1041	1134
Number (95% Confidence Interval) [Percentage of neonates]	4.72	5.21

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azithromycin + Chloroquine, Sulfadoxine + Pyrimethamine
	Comments	The 2-sided P-value tests the null hypothesis that the relative risk equals 1 (treatment group equality) versus not equal 1.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6086
	Comments	Mantel-Haenszel estimate of the common relative risk is presented, adjusting for randomization strata. A relative risk less than 1 favors Azithromycin + Chloroquine treatment group (reduction in risk for the endpoint).
	Method	Mantel Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.91
	Confidence Interval	(2-Sided) 95%; 0.63 to 1.31
	Parameter Dispersion	Type: Standard Deviation; Value: 0.1882
	Estimation Comments	The estimated risk ratio is presented along with its standard error (SE), with the SE on the log(e) scale.

5. Secondary Outcome

Title	Percentage of Participants With Severe Maternal Anemia (Hemoglobin [Hb] <8 g/dL) at 36-38 Weeks of Gestation
Description	Severe maternal anemia was defined as Hb <8 g/dL.
Time Frame	At 36-38 weeks of gestation.

Outcome Measure Data

Analysis Population Description

ITT set was used which consisted of participants who were randomized, received at least one dose of study medication (Day 0 at Visit 1 was considered the first dose of study medication), and who had a single fetus. N=Number of participants with Hb measurement at 36-38 weeks gestation.

Arm/Group Title	Azithromycin + Chloroquine	Sulfadoxine + Pyrimethamine
Arm/Group Description	The participants received 1000 mg Azithromycin (AZ) and 620 mg of Chloroquine (CQ) base (4 combination tablets of AZCQ with individual strength of 250 mg/155 mg), by mouth once daily for 3 days (Days 0, 1, 2) per treatment. There were a total of 3 treatments at 4-8 week intervals.	The participants received sulfadoxine-pyrimethamine (SP) (Fansidar) treatment course: 1500 mg sulfadoxine and 75 mg pyrimethamine (3 fixed tablets of SP strength at 500 mg/25 mg), single oral dose on Day 0 of each treatment. There were a total of 3 treatments at 4-8 week intervals.
Measure Participants	1222	1299
Number (95% Confidence Interval) [Percentage of participants]	1.80 0.1%	2.00 0.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azithromycin + Chloroquine, Sulfadoxine + Pyrimethamine
	Comments	The 2-sided P-value tests the null hypothesis that the relative risk equals 1 (treatment group equality) versus not equal 1.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7035
	Comments	Mantel-Haenszel estimate of the common relative risk is presented, adjusting for randomization strata. A relative risk less than 1 favors Azithromycin + Chloroquine treatment group (reduction in risk for the endpoint).
	Method	Mantel Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.90
	Confidence Interval	(2-Sided) 95%; 0.51 to 1.57
	Parameter Dispersion	Type: Standard Deviation; Value: 0.2866
	Estimation Comments	The estimated risk ratio is presented along with its standard error (SE), with the SE on the log(e) scale.

6. Secondary Outcome

Title	Percentage of Participants With Maternal Anemia (Hb <11 g/dL) at 36-38 Weeks of Gestation
Description	Anemia was defined as Hb <11 g/dL.
Time Frame	At 36-38 weeks of gestation.

Outcome Measure Data

Analysis Population Description

ITT set was used which consisted of participants who were randomized, received at least one dose of study medication (Day 0 at Visit 1 was considered the first dose of study medication), and who had a single fetus. N=Number of participants with Hb measurement at 36-38 weeks gestation.

Arm/Group Title	Azithromycin + Chloroquine	Sulfadoxine + Pyrimethamine
Arm/Group Description	The participants received 1000 mg Azithromycin (AZ) and 620 mg of Chloroquine (CQ) base (4 combination tablets of AZCQ with individual strength of 250 mg/155 mg), by mouth once daily for 3 days (Days 0, 1, 2) per treatment. There were a total of 3 treatments at 4-8 week intervals.	The participants received sulfadoxine-pyrimethamine (SP) (Fansidar) treatment course: 1500 mg sulfadoxine and 75 mg pyrimethamine (3 fixed tablets of SP strength at 500 mg/25 mg), single oral dose on Day 0 of each treatment. There were a total of 3 treatments at 4-8 week intervals.
Measure Participants	1222	1299
Number (95% Confidence Interval) [Percentage of Participants]	50.57 3.5%	49.11 3.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azithromycin + Chloroquine, Sulfadoxine + Pyrimethamine
	Comments	The 2-sided P-value tests the null hypothesis that the relative risk equals 1 (treatment group equality) versus not equal 1.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4605
	Comments	Mantel-Haenszel estimate of the common relative risk is presented, adjusting for randomization strata. A relative risk less than 1 favors Azithromycin + Chloroquine treatment group (reduction in risk for the endpoint).
	Method	Mantel Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.03
	Confidence Interval	(2-Sided) 95%; 0.95 to 1.11
	Parameter Dispersion	Type: Standard Deviation; Value: 0.0400
	Estimation Comments	The estimated risk ratio is presented along with its standard error (SE), with the SE on the log(e) scale.

7. Secondary Outcome

Title	Percentage of Participants With Placental Parasitemia at Delivery
Description	Participants with placental parasitemia at delivery were diagnosed using Placental blood smear at birth from participants who deliver at hospital.
Time Frame	Approximately 40 weeks of gestational age

Outcome Measure Data

Analysis Population Description

ITT set was used which consisted of participants who were randomized, received at least one dose of study medication (Day 0 at Visit 1 was considered the first dose of study medication), and who had a single fetus. N=Number of participants with placental parasite counts at delivery.

Arm/Group Title	Azithromycin + Chloroquine	Sulfadoxine + Pyrimethamine
Arm/Group Description	The participants received 1000 mg Azithromycin (AZ) and 620 mg of Chloroquine (CQ) base (4 combination tablets of AZCQ with individual strength of 250 mg/155 mg), by mouth once daily for 3 days (Days 0, 1, 2) per treatment. There were a total of 3 treatments at 4-8 week intervals.	The participants received sulfadoxine-pyrimethamine (SP) (Fansidar) treatment course: 1500 mg sulfadoxine and 75 mg pyrimethamine (3 fixed tablets of SP strength at 500 mg/25 mg), single oral dose on Day 0 of each treatment. There were a total of 3 treatments at 4-8 week intervals.
Measure Participants	1019	1076
Number (95% Confidence Interval) [Percentage of participants]	5.30 0.4%	5.67 0.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azithromycin + Chloroquine, Sulfadoxine + Pyrimethamine
	Comments	The 2-sided P-value tests the null hypothesis that the relative risk equals 1 (treatment group equality) versus not equal 1.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7105
	Comments	Mantel-Haenszel estimate of the common relative risk is presented, adjusting for randomization strata. A relative risk less than 1 favors Azithromycin + Chloroquine treatment group (reduction in risk for the endpoint).
	Method	Mantel Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.93
	Confidence Interval	(2-Sided) 95%; 0.65 to 1.33
	Parameter Dispersion	Type: Standard Deviation; Value: 0.1817
	Estimation Comments	The estimated risk ratio is presented along with its standard error (SE), with the SE on the log(e) scale.

8. Secondary Outcome

Title	Percentage of Participants With Placental Malaria at Delivery Based on Histology
Description	Participants positive for placental malaria at delivery were evaluated based on placental histology.
Time Frame	Approximately 40 weeks of gestational age

Outcome Measure Data

Analysis Population Description

ITT set was used which consisted of participants who were randomized, received at least one dose of study medication (Day 0 at Visit 1 was considered the first dose of study medication), and who had a single fetus. N=Number of participants with a histology parasite evaluation at delivery.

Arm/Group Title	Azithromycin + Chloroquine	Sulfadoxine + Pyrimethamine
Arm/Group Description	The participants received 1000 mg Azithromycin (AZ) and 620 mg of Chloroquine (CQ) base (4 combination tablets of AZCQ with individual strength of 250 mg/155 mg), by mouth once daily for 3 days (Days 0, 1, 2) per treatment. There were a total of 3 treatments at 4-8 week intervals.	The participants received sulfadoxine-pyrimethamine (SP) (Fansidar) treatment course: 1500 mg sulfadoxine and 75 mg pyrimethamine (3 fixed tablets of SP strength at 500 mg/25 mg), single oral dose on Day 0 of each treatment. There were a total of 3 treatments at 4-8 week intervals.
Measure Participants	1040	1100
Number (95% Confidence Interval) [Percentage of participants]	4.81 0.3%	5.73 0.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azithromycin + Chloroquine, Sulfadoxine + Pyrimethamine
	Comments	The 2-sided P-value tests the null hypothesis that the relative risk equals 1 (treatment group equality) versus not equal 1.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3468
	Comments	Mantel-Haenszel estimate of the common relative risk is presented, adjusting for randomization strata. A relative risk less than 1 favors Azithromycin + Chloroquine treatment group (reduction in risk for the endpoint).
	Method	Mantel Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.84
	Confidence Interval	(2-Sided) 95%; 0.59 to 1.21
	Parameter Dispersion	Type: Standard Deviation; Value: 0.1842
	Estimation Comments	The estimated risk ratio is presented along with its standard error (SE), with the SE on the log(e) scale.

9. Secondary Outcome

Title	Sexually Transmitted Infection (STI) Episodes Per Participant
Description	Number of episodes of sexually transmitted infection episodes per participant were noted. The STI's including Treponema pallidum, Neisseria gonorrhoeae, Chlamydia trachomatis, from first dose to delivery (diagnosis was based on clinical presentation and lab results).
Time Frame	Approximately 40 weeks of gestational age .

Outcome Measure Data

Analysis Population Description

ITT set was used which consisted of participants who were randomized, received at least one dose of study medication (Day 0 at Visit 1 was considered the first dose of study medication), and who had a single fetus. N=Number of participants with available data.

Arm/Group Title	Azithromycin + Chloroquine	Sulfadoxine + Pyrimethamine
Arm/Group Description	The participants received 1000 mg Azithromycin (AZ) and 620 mg of Chloroquine (CQ) base (4 combination tablets of AZCQ with individual strength of 250 mg/155 mg), by mouth once daily for 3 days (Days 0, 1, 2) per treatment. There were a total of 3 treatments at 4-8 week intervals.	The participants received sulfadoxine-pyrimethamine (SP) (Fansidar) treatment course: 1500 mg sulfadoxine and 75 mg pyrimethamine (3 fixed tablets of SP strength at 500 mg/25 mg), single oral dose on Day 0 of each treatment. There were a total of 3 treatments at 4-8 week intervals.
Measure Participants	1445	1445
Least Squares Mean (95% Confidence Interval) [Number of episodes]	0.14	0.19

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azithromycin + Chloroquine, Sulfadoxine + Pyrimethamine
	Comments	The 2-sided P-value tests the null hypothesis that the mean difference is 0 (treatment group equality) versus not equal 0.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0011
	Comments	Analysis based on an ANOVA model with model terms for treatment group and randomization stratification variable. A negative mean difference between treatment groups favors Azithromycin + Chloroquine (reduction in number of STIs).
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.05
	Confidence Interval	(2-Sided) 95%; -0.08 to -0.02
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.02
	Estimation Comments

10. Secondary Outcome

Title	Percentage of Participants With Sub-optimal Pregnancy Outcome Including Neonatal Death and Congenital Malformation
Description	Sub-optimal pregnancy outcome including neonatal deaths and congenital malformations, defined as any of the following: live-borne neonate (singleton) with low birth-weight (or LBW for short, defined as live birth weight <2,500g), premature birth (<37 weeks), abortion (≤28 weeks), still birth (>28 weeks), neonatal death, congenital malformation, lost to follow-up prior to termination of pregnancy or delivery, or missing birth weight of the neonates.
Time Frame	Approximately 40 weeks of gestational age.

Outcome Measure Data

Analysis Population Description

ITT set was used which consisted of participants who were randomized, received at least one dose of study medication (Day 0 at Visit 1 was considered the first dose of study medication), and who had a single fetus. N=Total Outcomes.

Arm/Group Title	Azithromycin + Chloroquine	Sulfadoxine + Pyrimethamine
Arm/Group Description	The participants received 1000 mg Azithromycin (AZ) and 620 mg of Chloroquine (CQ) base (4 combination tablets of AZCQ with individual strength of 250 mg/155 mg), by mouth once daily for 3 days (Days 0, 1, 2) per treatment. There were a total of 3 treatments at 4-8 week intervals.	The participants received sulfadoxine-pyrimethamine (SP) (Fansidar) treatment course: 1500 mg sulfadoxine and 75 mg pyrimethamine (3 fixed tablets of SP strength at 500 mg/25 mg), single oral dose on Day 0 of each treatment. There were a total of 3 treatments at 4-8 week intervals.
Measure Participants	1445	1445
Number (95% Confidence Interval) [Percentage of participants]	28.51 2%	26.51 1.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azithromycin + Chloroquine, Sulfadoxine + Pyrimethamine
	Comments	The 2-sided P-value tests the null hypothesis that the relative risk equals 1 (treatment group equality) versus not equal 1.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2265
	Comments	Mantel-Haenszel estimate of the common relative risk is presented, adjusting for randomization strata. A relative risk less than 1 favors Azithromycin + Chloroquine treatment group (reduction in risk for the endpoint).
	Method	Mantel Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.08
	Confidence Interval	(2-Sided) 95%; 0.96 to 1.21
	Parameter Dispersion	Type: Standard Deviation; Value: 0.0604
	Estimation Comments	The estimated risk ratio is presented along with its standard error (SE), with the SE on the log(e) scale.

11. Secondary Outcome

Title	Change From Baseline to 36-38 Weeks of Gestation in Hb Concentration.
Description	Change from Baseline to 36-38 weeks of gestation in Hb concentration was noted.
Time Frame	Baseline, at 36-38 weeks of gestation.

Outcome Measure Data

Analysis Population Description

ITT set was used which consisted of participants who were randomized, received at least one dose of study medication (Day 0 at Visit 1 was considered the first dose of study medication), and who had a single fetus. N=Number of participants with available data.

Arm/Group Title	Azithromycin + Chloroquine	Sulfadoxine + Pyrimethamine
Arm/Group Description	The participants received 1000 mg Azithromycin (AZ) and 620 mg of Chloroquine (CQ) base (4 combination tablets of AZCQ with individual strength of 250 mg/155 mg), by mouth once daily for 3 days (Days 0, 1, 2) per treatment. There were a total of 3 treatments at 4-8 week intervals.	The participants received sulfadoxine-pyrimethamine (SP) (Fansidar) treatment course: 1500 mg sulfadoxine and 75 mg pyrimethamine (3 fixed tablets of SP strength at 500 mg/25 mg), single oral dose on Day 0 of each treatment. There were a total of 3 treatments at 4-8 week intervals.
Measure Participants	1221	1298
Least Squares Mean (95% Confidence Interval) [g/dL]	0.13	0.27

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azithromycin + Chloroquine, Sulfadoxine + Pyrimethamine
	Comments	The 2-sided P-value tests the null hypothesis that the mean difference is 0 (treatment group equality) versus not equal 0.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0131
	Comments	Analysis based on an ANCOVA model with model terms for baseline value, treatment group and randomization stratification variable.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.14
	Confidence Interval	(2-Sided) 95%; -0.24 to -0.03
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.05
	Estimation Comments

12. Secondary Outcome

Title	Percentage of Neonates With Congenital Abnormalities at Birth
Description	Neonates with congenital abnormalities at birth were noted.
Time Frame	Approximately 40 weeks of gestational age.

Outcome Measure Data

Analysis Population Description

ITT set was used which consisted of participants who were randomized, received at least one dose of study medication (Day 0 at Visit 1 was considered the first dose of study medication), and who had a single fetus. N=Number of total live births.

Arm/Group Title	Azithromycin + Chloroquine	Sulfadoxine + Pyrimethamine
Arm/Group Description	The participants received 1000 mg Azithromycin (AZ) and 620 mg of Chloroquine (CQ) base (4 combination tablets of AZCQ with individual strength of 250 mg/155 mg), by mouth once daily for 3 days (Days 0, 1, 2) per treatment. There were a total of 3 treatments at 4-8 week intervals.	The participants received sulfadoxine-pyrimethamine (SP) (Fansidar) treatment course: 1500 mg sulfadoxine and 75 mg pyrimethamine (3 fixed tablets of SP strength at 500 mg/25 mg), single oral dose on Day 0 of each treatment. There were a total of 3 treatments at 4-8 week intervals.
Measure Participants	1140	1190
Number (95% Confidence Interval) [Percentage of neonates]	2.19	2.44

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azithromycin + Chloroquine, Sulfadoxine + Pyrimethamine
	Comments	The 2-sided P-value tests the null hypothesis that the relative risk equals 1 (treatment group equality) versus not equal 1.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6978
	Comments	Mantel-Haenszel estimate of the common relative risk is presented, adjusting for randomization strata. A relative risk less than 1 favors Azithromycin + Chloroquine treatment group (reduction in risk for the endpoint).
	Method	Mantel Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.90
	Confidence Interval	(2-Sided) 95%; 0.53 to 1.53
	Parameter Dispersion	Type: Standard Deviation; Value: 0.2694
	Estimation Comments	The estimated risk ratio is presented along with its SE, with the SE on the log(e) scale.

13. Secondary Outcome

Title	Percentage of Perinatal or Neonatal Deaths
Description	Percentage of perinatal or neonatal deaths were noted.
Time Frame	Day 28 after delivery.

Outcome Measure Data

Analysis Population Description

ITT set was used which consisted of participants who were randomized, received at least one dose of study medication (Day 0 at Visit 1 was considered the first dose of study medication), and who had a single fetus. N=Number of total live births.

Arm/Group Title	Azithromycin + Chloroquine	Sulfadoxine + Pyrimethamine
Arm/Group Description	The participants received 1000 mg Azithromycin (AZ) and 620 mg of Chloroquine (CQ) base (4 combination tablets of AZCQ with individual strength of 250 mg/155 mg), by mouth once daily for 3 days (Days 0, 1, 2) per treatment. There were a total of 3 treatments at 4-8 week intervals.	The participants received sulfadoxine-pyrimethamine (SP) (Fansidar) treatment course: 1500 mg sulfadoxine and 75 mg pyrimethamine (3 fixed tablets of SP strength at 500 mg/25 mg), single oral dose on Day 0 of each treatment. There were a total of 3 treatments at 4-8 week intervals.
Measure Participants	1140	1190
Number (95% Confidence Interval) [Percentage of neonates]	2.19	1.85

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azithromycin + Chloroquine, Sulfadoxine + Pyrimethamine
	Comments	The 2-sided P-value tests the null hypothesis that the relative risk equals 1 (treatment group equality) versus not equal 1.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6542
	Comments	Mantel-Haenszel estimate of the common relative risk is presented, adjusting for randomization strata. A relative risk less than 1 favors Azithromycin + Chloroquine treatment group (reduction in risk for the endpoint).
	Method	Mantel Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.14
	Confidence Interval	(2-Sided) 95%; 0.64 to 2.01
	Parameter Dispersion	Type: Standard Deviation; Value: 0.2908
	Estimation Comments	The estimated risk ratio is presented along with its SE, with the SE on the log(e) scale.

14. Secondary Outcome

Title	Birth Weight of Live Borne Neonate
Description	Birth weight of live borne neonates were calculated in grams.
Time Frame	Approximately 40 weeks of gestational age.

Outcome Measure Data

Analysis Population Description

ITT set was used which consisted of participants who were randomized, received at least one dose of study medication (Day 0 at Visit 1 was considered the first dose of study medication), and who had a single fetus. N=Number of live births with available data.

Arm/Group Title	Azithromycin + Chloroquine	Sulfadoxine + Pyrimethamine
Arm/Group Description	The participants received 1000 mg Azithromycin (AZ) and 620 mg of Chloroquine (CQ) base (4 combination tablets of AZCQ with individual strength of 250 mg/155 mg), by mouth once daily for 3 days (Days 0, 1, 2) per treatment. There were a total of 3 treatments at 4-8 week intervals.	The participants received sulfadoxine-pyrimethamine (SP) (Fansidar) treatment course: 1500 mg sulfadoxine and 75 mg pyrimethamine (3 fixed tablets of SP strength at 500 mg/25 mg), single oral dose on Day 0 of each treatment. There were a total of 3 treatments at 4-8 week intervals.
Measure Participants	1138	1188
Least Squares Mean (95% Confidence Interval) [grams]	3148.3	3146.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azithromycin + Chloroquine, Sulfadoxine + Pyrimethamine
	Comments	The 2-sided P-value tests the null hypothesis that the mean difference is 0 (treatment group equality) versus not equal 0.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9145
	Comments	Analysis based on an ANOVA model with model terms for treatment group and randomization stratification variable.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	2.1
	Confidence Interval	(2-Sided) 95%; -36.5 to 40.8
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 19.71
	Estimation Comments

15. Secondary Outcome

Title	Number of Episodes of Symptomatic Malaria Per Participant From First Intermittent Preventive Treatment of Falciparum Dose to Delivery
Description	This outcome measure determined if an episode of malaria started within the time period of first dose to delivery. Clinical episode of malaria was determined if the participant presented with clinical symptoms of malaria (fever >37.5°C, oral) and diagnosed (either by rapid diagnostic tests or microscopy) with malaria.
Time Frame	Approximately 40 weeks of gestational age

Outcome Measure Data

Analysis Population Description

ITT set was used which consisted of participants who were randomized, received at least one dose of study medication (Day 0 at Visit 1 is considered the first dose of study medication), and who had a single fetus.

Arm/Group Title	Azithromycin + Chloroquine	Sulfadoxine + Pyrimethamine
Arm/Group Description	The participants received 1000 mg Azithromycin (AZ) and 620 mg of Chloroquine (CQ) base (4 combination tablets of AZCQ with individual strength of 250 mg/155 mg), by mouth once daily for 3 days (Days 0, 1, 2) per treatment. There were a total of 3 treatments at 4-8 week intervals.	The participants received sulfadoxine-pyrimethamine (SP) (Fansidar) treatment course: 1500 mg sulfadoxine and 75 mg pyrimethamine (3 fixed tablets of SP strength at 500 mg/25 mg), single oral dose on Day 0 of each treatment. There were a total of 3 treatments at 4-8 week intervals.
Measure Participants	1445	1445
Least Squares Mean (95% Confidence Interval) [Number of episodes]	0.06	0.13

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azithromycin + Chloroquine, Sulfadoxine + Pyrimethamine
	Comments	The 2-sided P-value tests the null hypothesis that the mean difference is 0 (treatment group equality) versus not equal 0.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Analysis based on an ANOVA model with model terms for treatment group and randomization stratification variable. A negative mean difference between treatment groups favors Azithromycin + Chloroquine (reduction in number of symptomatic malaria).
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.07
	Confidence Interval	(2-Sided) 95%; -0.09 to -0.04
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.01
	Estimation Comments

16. Secondary Outcome

Title	Percentage of Participants Requiring Additional Treatment for Symptomatic Malaria From First Dose to Delivery
Description	This outcome measure evaluated the participants requiring additional treatments for malaria during the study period following the first dose (diagnosed based on clinical presentation and/or lab test results).
Time Frame	Approximately 40 weeks of gestational age

Outcome Measure Data

Analysis Population Description

ITT set was used which consisted of participants who were randomized, received at least one dose of study medication (Day 0 at Visit 1 is considered the first dose of study medication), and who had a single fetus.

Arm/Group Title	Azithromycin + Chloroquine	Sulfadoxine + Pyrimethamine
Arm/Group Description	The participants received 1000 mg Azithromycin (AZ) and 620 mg of Chloroquine (CQ) base (4 combination tablets of AZCQ with individual strength of 250 mg/155 mg), by mouth once daily for 3 days (Days 0, 1, 2) per treatment. There were a total of 3 treatments at 4-8 week intervals.	The participants received sulfadoxine-pyrimethamine (SP) (Fansidar) treatment course: 1500 mg sulfadoxine and 75 mg pyrimethamine (3 fixed tablets of SP strength at 500 mg/25 mg), single oral dose on Day 0 of each treatment. There were a total of 3 treatments at 4-8 week intervals.
Measure Participants	1445	1445
Number (95% Confidence Interval) [Percentage of participants]	5.74 0.4%	10.52 0.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azithromycin + Chloroquine, Sulfadoxine + Pyrimethamine
	Comments	The 2-sided P-value tests the null hypothesis that the relative risk equals 1 (treatment group equality) versus not equal 1.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Mantel-Haenszel estimate of the common relative risk is presented, adjusting for randomization strata. A relative risk less than 1 favors Azithromycin + Chloroquine treatment group (reduction in risk for the endpoint).
	Method	Mantel Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.49
	Confidence Interval	(2-Sided) 95%; 0.38 to 0.62
	Parameter Dispersion	Type: Standard Deviation; Value: 0.1221
	Estimation Comments	The estimated risk ratio is presented along with its standard error (SE), with the SE on the log(e) scale.

17. Secondary Outcome

Title	Percentage of Participants With Peripheral Parasitemia at 36-38 Weeks of Gestation
Description	This outcome measure evaluated the percentage of participants positive for peripheral parasitemia at 36-38 weeks of gestation. A participant was positive for parasitemia if the number of asexual parasites per μL was >0.
Time Frame	At 36-38 weeks of gestation

Outcome Measure Data

Analysis Population Description

ITT set was used which consisted of participants who were randomized, received at least one dose of study medication (Day 0 at Visit 1 is considered the first dose of study medication), and who had a single fetus. N = Number of participants with peripheral blood smear parasite counts at 36-38 weeks of gestation.

Arm/Group Title	Azithromycin + Chloroquine	Sulfadoxine + Pyrimethamine
Arm/Group Description	The participants received 1000 mg Azithromycin (AZ) and 620 mg of Chloroquine (CQ) base (4 combination tablets of AZCQ with individual strength of 250 mg/155 mg), by mouth once daily for 3 days (Days 0, 1, 2) per treatment. There were a total of 3 treatments at 4-8 week intervals.	The participants received sulfadoxine-pyrimethamine (SP) (Fansidar) treatment course: 1500 mg sulfadoxine and 75 mg pyrimethamine (3 fixed tablets of SP strength at 500 mg/25 mg), single oral dose on Day 0 of each treatment. There were a total of 3 treatments at 4-8 week intervals.
Measure Participants	1069	1142
Number (95% Confidence Interval) [Percentage of participants]	2.71 0.2%	4.38 0.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azithromycin + Chloroquine, Sulfadoxine + Pyrimethamine
	Comments	The 2-sided P-value tests the null hypothesis that the relative risk equals 1 (treatment group equality) versus not equal 1.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0360
	Comments	Mantel-Haenszel estimate of the common relative risk is presented, adjusting for randomization strata. A relative risk less than 1 favors Azithromycin + Chloroquine treatment group (reduction in risk for the endpoint).
	Method	Mantel Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.62
	Confidence Interval	(2-Sided) 95%; 0.39 to 0.97
	Parameter Dispersion	Type: Standard Deviation; Value: 0.2295
	Estimation Comments	The estimated risk ratio is presented along with its SE, with the SE on the log(e) scale.

18. Secondary Outcome

Title	Percentage of Participants With Peripheral Parasitemia at Delivery
Description	This outcome measure evaluated the percentage of participants positive for peripheral parasitemia at delivery. A participant was positive for parasitemia if the number of asexual parasites per μL was >0.
Time Frame	Approximately 40 weeks of gestational age

Outcome Measure Data

Analysis Population Description

ITT set was used which consisted of participants who were randomized, received at least one dose of study medication (Day 0 at Visit 1 is considered the first dose of study medication), and who had a single fetus. N = Number of participants with peripheral blood smear parasite counts at delivery.

Arm/Group Title	Azithromycin + Chloroquine	Sulfadoxine + Pyrimethamine
Arm/Group Description	The participants received 1000 mg Azithromycin (AZ) and 620 mg of Chloroquine (CQ) base (4 combination tablets of AZCQ with individual strength of 250 mg/155 mg), by mouth once daily for 3 days (Days 0, 1, 2) per treatment. There were a total of 3 treatments at 4-8 week intervals.	The participants received sulfadoxine-pyrimethamine (SP) (Fansidar) treatment course: 1500 mg sulfadoxine and 75 mg pyrimethamine (3 fixed tablets of SP strength at 500 mg/25 mg), single oral dose on Day 0 of each treatment. There were a total of 3 treatments at 4-8 week intervals.
Measure Participants	1025	1086
Number (95% Confidence Interval) [Percentage of participants]	6.05 0.4%	7.46 0.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azithromycin + Chloroquine, Sulfadoxine + Pyrimethamine
	Comments	The 2-sided P-value tests the null hypothesis that the relative risk equals 1 (treatment group equality) versus not equal 1.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1975
	Comments	Mantel-Haenszel estimate of the common relative risk is presented, adjusting for randomization strata. A relative risk less than 1 favors Azithromycin + Chloroquine treatment group (reduction in risk for the endpoint).
	Method	Mantel Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.81
	Confidence Interval	(2-Sided) 95%; 0.59 to 1.12
	Parameter Dispersion	Type: Standard Deviation; Value: 0.1630
	Estimation Comments	The estimated risk ratio is presented along with its standard error (SE), with the SE on the log(e) scale.

19. Secondary Outcome

Title	Percentage of Participants With Cord Blood Parasitemia at Delivery
Description	This outcome measure evaluated the percentage of participants positive for cord blood parasitemia at delivery. A participant was positive for parasitemia if the number of asexual parasites per μL was >0.
Time Frame	Approximately 40 weeks of gestational age

Outcome Measure Data

Analysis Population Description

ITT set was used which consisted of participants who were randomized, received at least one dose of study medication (Day 0 at Visit 1 is considered the first dose of study medication), and who had a single fetus. N = Number of participants with cord blood smear parasite counts at delivery.

Arm/Group Title	Azithromycin + Chloroquine	Sulfadoxine + Pyrimethamine
Arm/Group Description	The participants received 1000 mg Azithromycin (AZ) and 620 mg of Chloroquine (CQ) base (4 combination tablets of AZCQ with individual strength of 250 mg/155 mg), by mouth once daily for 3 days (Days 0, 1, 2) per treatment. There were a total of 3 treatments at 4-8 week intervals.	The participants received sulfadoxine-pyrimethamine (SP) (Fansidar) treatment course: 1500 mg sulfadoxine and 75 mg pyrimethamine (3 fixed tablets of SP strength at 500 mg/25 mg), single oral dose on Day 0 of each treatment. There were a total of 3 treatments at 4-8 week intervals.
Measure Participants	1015	1072
Number (95% Confidence Interval) [Percentage of participants]	0.49 0%	0.75 0.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azithromycin + Chloroquine, Sulfadoxine + Pyrimethamine
	Comments	The 2-sided P-value tests the null hypothesis that the relative risk equals 1 (treatment group equality) versus not equal 1.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4655
	Comments	Mantel-Haenszel estimate of the common relative risk is presented, adjusting for randomization strata. A relative risk less than 1 favors Azithromycin + Chloroquine treatment group (reduction in risk for the endpoint).
	Method	Mantel Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.66
	Confidence Interval	(2-Sided) 95%; 0.22 to 2.01
	Parameter Dispersion	Type: Standard Deviation; Value: 0.5675
	Estimation Comments	The estimated risk ratio is presented along with its SE, with the SE on the log(e) scale.

20. Secondary Outcome

Title	Percentage of Participants With Sexually Transmitted Infections From First Dose to 36-38 Weeks of Gestation
Description	Sexual transmitted disease included Treponema pallidum, Neisseria gonorrhoeae, and Chlamydia trachomatis infections. This was diagnosed based on clinical presentation prior to Week 36-38 and/or lab test results between Week 36-38.
Time Frame	Upto 36-38 weeks of gestation

Outcome Measure Data

Analysis Population Description

ITT set was used which consisted of participants who were randomized, received at least one dose of study medication (Day 0 at Visit 1 is considered the first dose of study medication), and who had a single fetus.

Arm/Group Title	Azithromycin + Chloroquine	Sulfadoxine + Pyrimethamine
Arm/Group Description	The participants received 1000 mg Azithromycin (AZ) and 620 mg of Chloroquine (CQ) base (4 combination tablets of AZCQ with individual strength of 250 mg/155 mg), by mouth once daily for 3 days (Days 0, 1, 2) per treatment. There were a total of 3 treatments at 4-8 week intervals.	The participants received sulfadoxine-pyrimethamine (SP) (Fansidar) treatment course: 1500 mg sulfadoxine and 75 mg pyrimethamine (3 fixed tablets of SP strength at 500 mg/25 mg), single oral dose on Day 0 of each treatment. There were a total of 3 treatments at 4-8 week intervals.
Measure Participants	1445	1445
Number (95% Confidence Interval) [Percentage of participants]	12.32 0.9%	16.47 1.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azithromycin + Chloroquine, Sulfadoxine + Pyrimethamine
	Comments	The 2-sided P-value tests the null hypothesis that the relative risk equals 1 (treatment group equality) versus not equal 1.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0016
	Comments	Mantel-Haenszel estimate of the common relative risk is presented, adjusting for randomization strata. A relative risk less than 1 favors Azithromycin + Chloroquine treatment group (reduction in risk for the endpoint).
	Method	Mantel Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.75
	Confidence Interval	(2-Sided) 95%; 0.62 to 0.90
	Parameter Dispersion	Type: Standard Deviation; Value: 0.0918
	Estimation Comments	The estimated risk ratio is presented along with its standard error (SE), with the SE on the log(e) scale.

21. Secondary Outcome

Title	Percentage of Participants With Chlamydia Trachomatis Infection at 36-38 Weeks of Gestation
Description	Participants positive for Chlamydia trachomatis infection was diagnosed based on laboratory result at 36-38 weeks of gestation. A vaginal swab was collected and PCR assay was used for analysis.
Time Frame	At 36-38 weeks of gestation

Outcome Measure Data

Analysis Population Description

ITT set was used which consisted of participants who were randomized, received at least one dose of study medication (Day 0 at Visit 1 is considered the first dose of study medication), and who had a single fetus. N=Number of participants with lab test results at 36-38 weeks of gestation.

Arm/Group Title	Azithromycin + Chloroquine	Sulfadoxine + Pyrimethamine
Arm/Group Description	The participants received 1000 mg Azithromycin (AZ) and 620 mg of Chloroquine (CQ) base (4 combination tablets of AZCQ with individual strength of 250 mg/155 mg), by mouth once daily for 3 days (Days 0, 1, 2) per treatment. There were a total of 3 treatments at 4-8 week intervals.	The participants received sulfadoxine-pyrimethamine (SP) (Fansidar) treatment course: 1500 mg sulfadoxine and 75 mg pyrimethamine (3 fixed tablets of SP strength at 500 mg/25 mg), single oral dose on Day 0 of each treatment. There were a total of 3 treatments at 4-8 week intervals.
Measure Participants	746	794
Number (95% Confidence Interval) [Percentage of participants]	1.47 0.1%	0.63 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azithromycin + Chloroquine, Sulfadoxine + Pyrimethamine
	Comments	The 2-sided P-value tests the null hypothesis that the relative risk equals 1 (treatment group equality) versus not equal 1.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1113
	Comments	Mantel-Haenszel estimate of the common relative risk is presented, adjusting for randomization strata. A relative risk less than 1 favors Azithromycin + Chloroquine treatment group (reduction in risk for the endpoint).
	Method	Mantel Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	2.34
	Confidence Interval	(2-Sided) 95%; 0.82 to 6.66
	Parameter Dispersion	Type: Standard Deviation; Value: 0.5338
	Estimation Comments	The estimated risk ratio is presented along with its standard error (SE), with the SE on the log(e) scale.

22. Secondary Outcome

Title	Percentage of Participants With Neisseria Gonorrhoeae Infection at 36-38 Weeks of Gestation
Description	Participants positive for Neisseria gonorrhoeae infection was diagnosed based on laboratory result at 36-38 weeks of gestation. A vaginal swab was collected and PCR assay was used for analysis.
Time Frame	At 36-38 weeks of gestation

Outcome Measure Data

Analysis Population Description

ITT set was used which consisted of participants who were randomized, received at least one dose of study medication (Day 0 at Visit 1 is considered the first dose of study medication), and who had a single fetus. N=Number of participants with laboratory test results at 36-38 weeks of gestation.

Arm/Group Title	Azithromycin + Chloroquine	Sulfadoxine + Pyrimethamine
Arm/Group Description	The participants received 1000 mg Azithromycin (AZ) and 620 mg of Chloroquine (CQ) base (4 combination tablets of AZCQ with individual strength of 250 mg/155 mg), by mouth once daily for 3 days (Days 0, 1, 2) per treatment. There were a total of 3 treatments at 4-8 week intervals.	The participants received sulfadoxine-pyrimethamine (SP) (Fansidar) treatment course: 1500 mg sulfadoxine and 75 mg pyrimethamine (3 fixed tablets of SP strength at 500 mg/25 mg), single oral dose on Day 0 of each treatment. There were a total of 3 treatments at 4-8 week intervals.
Measure Participants	746	794
Number (95% Confidence Interval) [Percentage of participants]	0.40 0%	1.64 0.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azithromycin + Chloroquine, Sulfadoxine + Pyrimethamine
	Comments	The 2-sided P-value tests the null hypothesis that the relative risk equals 1 (treatment group equality) versus not equal 1.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0284
	Comments	Mantel-Haenszel estimate of the common relative risk is presented, adjusting for randomization strata. A relative risk less than 1 favors Azithromycin + Chloroquine treatment group (reduction in risk for the endpoint).
	Method	Mantel Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.25
	Confidence Interval	(2-Sided) 95%; 0.07 to 0.86
	Parameter Dispersion	Type: Standard Deviation; Value: 0.6386
	Estimation Comments	The estimated risk ratio is presented along with its standard error (SE), with the SE on the log(e) scale.

23. Secondary Outcome

Title	Percentage of Participants With Treponema Pallidum Infection at 36-38 Weeks of Gestation
Description	Participants positive for Treponema pallidum infection was diagnosed based on laboratory result at 36-38 weeks of gestation. Treponema Pallidum particle Agglutination Assay was used.
Time Frame	At 36-38 weeks of gestation

Outcome Measure Data

Analysis Population Description

ITT set was used which consisted of participants who were randomized, received at least one dose of study medication (Day 0 at Visit 1 is considered the first dose of study medication), and who had a single fetus. N=Number of participants with laboratory test results at 36-38 weeks of gestation.

Arm/Group Title	Azithromycin + Chloroquine	Sulfadoxine + Pyrimethamine
Arm/Group Description	The participants received 1000 mg Azithromycin (AZ) and 620 mg of Chloroquine (CQ) base (4 combination tablets of AZCQ with individual strength of 250 mg/155 mg), by mouth once daily for 3 days (Days 0, 1, 2) per treatment. There were a total of 3 treatments at 4-8 week intervals.	The participants received sulfadoxine-pyrimethamine (SP) (Fansidar) treatment course: 1500 mg sulfadoxine and 75 mg pyrimethamine (3 fixed tablets of SP strength at 500 mg/25 mg), single oral dose on Day 0 of each treatment. There were a total of 3 treatments at 4-8 week intervals.
Measure Participants	751	797
Number (95% Confidence Interval) [Percentage of participants]	0.93 0.1%	2.01 0.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azithromycin + Chloroquine, Sulfadoxine + Pyrimethamine
	Comments	The 2-sided P-value tests the null hypothesis that the relative risk equals 1 (treatment group equality) versus not equal 1.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0188
	Comments	Mantel-Haenszel estimate of the common relative risk is presented, adjusting for randomization strata. A relative risk less than 1 favors Azithromycin + Chloroquine treatment group (reduction in risk for the endpoint).
	Method	Mantel Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.46
	Confidence Interval	(2-Sided) 95%; 0.24 to 0.88
	Parameter Dispersion	Type: Standard Deviation; Value: 0.3291
	Estimation Comments	The estimated risk ratio is presented along with its standard error (SE), with the SE on the log(e) scale.

24. Secondary Outcome

Title	Percentage of Participants With Trichomonas Vaginalis Infection at 36-38 Weeks of Gestation
Description	Participants positive for Trichomonas vaginalis infection was diagnosed based on laboratory result at 36-38 weeks of gestation. A vaginal swab was collected for the laboratory test.
Time Frame	At 36-38 weeks of gestation

Outcome Measure Data

Analysis Population Description

ITT set was used which consisted of participants who were randomized, received at least one dose of study medication (Day 0 at Visit 1 is considered the first dose of study medication), and who had a single fetus. N=Number of participants with laboratory test results at 36-38 weeks of gestation.

Arm/Group Title	Azithromycin + Chloroquine	Sulfadoxine + Pyrimethamine
Arm/Group Description	The participants received 1000 mg Azithromycin (AZ) and 620 mg of Chloroquine (CQ) base (4 combination tablets of AZCQ with individual strength of 250 mg/155 mg), by mouth once daily for 3 days (Days 0, 1, 2) per treatment. There were a total of 3 treatments at 4-8 week intervals.	The participants received sulfadoxine-pyrimethamine (SP) (Fansidar) treatment course: 1500 mg sulfadoxine and 75 mg pyrimethamine (3 fixed tablets of SP strength at 500 mg/25 mg), single oral dose on Day 0 of each treatment. There were a total of 3 treatments at 4-8 week intervals.
Measure Participants	1068	1143
Number (95% Confidence Interval) [Percentage of participants]	8.24 0.6%	10.67 0.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azithromycin + Chloroquine, Sulfadoxine + Pyrimethamine
	Comments	The 2-sided P-value tests the null hypothesis that the relative risk equals 1 (treatment group equality) versus not equal 1.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0527
	Comments	Mantel-Haenszel estimate of the common relative risk is presented, adjusting for randomization strata. A relative risk less than 1 favors Azithromycin + Chloroquine treatment group (reduction in risk for the endpoint).
	Method	Mantel Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.77
	Confidence Interval	(2-Sided) 95%; 0.59 to 1.00
	Parameter Dispersion	Type: Standard Deviation; Value: 0.1336
	Estimation Comments	The estimated risk ratio is presented along with its standard error (SE), with the SE on the log(e) scale.

25. Secondary Outcome

Title	Percentage of Participants With Bacterial Vaginosis Infection at 36-38 Weeks of Gestation.
Description	Bacterial vaginosis was diagnosed based on laboratory result at 36-38 weeks of gestation. A vaginal swab was collected for the Gram staining.
Time Frame	At 36-38 weeks of gestation

Outcome Measure Data

Analysis Population Description

ITT set was used which consisted of participants who were randomized, received at least one dose of study medication (Day 0 at Visit 1 is considered the first dose of study medication), and who had a single fetus. N=Number of participants with laboratory test results at 36-38 weeks of gestation.

Arm/Group Title	Azithromycin + Chloroquine	Sulfadoxine + Pyrimethamine
Arm/Group Description	The participants received 1000 mg Azithromycin (AZ) and 620 mg of Chloroquine (CQ) base (4 combination tablets of AZCQ with individual strength of 250 mg/155 mg), by mouth once daily for 3 days (Days 0, 1, 2) per treatment. There were a total of 3 treatments at 4-8 week intervals.	The participants received sulfadoxine-pyrimethamine (SP) (Fansidar) treatment course: 1500 mg sulfadoxine and 75 mg pyrimethamine (3 fixed tablets of SP strength at 500 mg/25 mg), single oral dose on Day 0 of each treatment. There were a total of 3 treatments at 4-8 week intervals.
Measure Participants	746	794
Number (95% Confidence Interval) [Percentage of participants]	8.58 0.6%	11.84 0.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azithromycin + Chloroquine, Sulfadoxine + Pyrimethamine
	Comments	The 2-sided P-value tests the null hypothesis that the relative risk equals 1 (treatment group equality) versus not equal 1.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0384
	Comments	Mantel-Haenszel estimate of the common relative risk is presented, adjusting for randomization strata. A relative risk less than 1 favors Azithromycin + Chloroquine treatment group (reduction in risk for the endpoint).
	Method	Mantel Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.73
	Confidence Interval	(2-Sided) 95%; 0.54 to 0.98
	Parameter Dispersion	Type: Standard Deviation; Value: 0.1536
	Estimation Comments	The estimated risk ratio is presented along with its standard error (SE), with the SE on the log(e) scale.

26. Secondary Outcome

Title	Percentage of Neonates With Ophthalmia Neonatorum at Birth Period
Description	Ophthalmia neonatorum was diagnosed at birth. The laboratory diagnosis was performed among neonates with purulent discharge.
Time Frame	Approximately 40 weeks of gestational age

Outcome Measure Data

Analysis Population Description

ITT set was used which consisted of participants who were randomized, received at least one dose of study medication (Day 0 at Visit 1 is considered the first dose of study medication), and who had a single fetus. N=Total live births.

Arm/Group Title	Azithromycin + Chloroquine	Sulfadoxine + Pyrimethamine
Arm/Group Description	The participants received 1000 mg Azithromycin (AZ) and 620 mg of Chloroquine (CQ) base (4 combination tablets of AZCQ with individual strength of 250 mg/155 mg), by mouth once daily for 3 days (Days 0, 1, 2) per treatment. There were a total of 3 treatments at 4-8 week intervals.	The participants received sulfadoxine-pyrimethamine (SP) (Fansidar) treatment course: 1500 mg sulfadoxine and 75 mg pyrimethamine (3 fixed tablets of SP strength at 500 mg/25 mg), single oral dose on Day 0 of each treatment. There were a total of 3 treatments at 4-8 week intervals.
Measure Participants	1140	1190
Number (95% Confidence Interval) [Percentage of neonates]	0.35	0.17

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azithromycin + Chloroquine, Sulfadoxine + Pyrimethamine
	Comments	The 2-sided P-value tests the null hypothesis that the relative risk equals 1 (treatment group equality) versus not equal 1.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3942
	Comments	Mantel-Haenszel estimate of the common relative risk is presented, adjusting for randomization strata. A relative risk less than 1 favors Azithromycin + Chloroquine treatment group (reduction in risk for the endpoint).
	Method	Mantel Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	2.09
	Confidence Interval	(2-Sided) 95%; 0.38 to 11.38
	Parameter Dispersion	Type: Standard Deviation; Value: 0.8648
	Estimation Comments	The estimated risk ratio is presented along with its standard error (SE), with the SE on the log(e) scale.

27. Secondary Outcome

Title	Percentage of Participants With Bacterial Infections Including Pneumonia and Other Lower Respiratory Tract Infections From First Dose to Delivery
Description	Participants positive for bacterial infections including other lower respiratory tract infections were measured anytime from first dose administration to delivery.
Time Frame	Up to approximately 40 weeks of gestational age

Outcome Measure Data

Analysis Population Description

ITT set was used which consisted of participants who were randomized, received at least one dose of study medication (Day 0 at Visit 1 is considered the first dose of study medication), and who had a single fetus. N=Number of participants with available data.

Arm/Group Title	Azithromycin + Chloroquine	Sulfadoxine + Pyrimethamine
Arm/Group Description	The participants received 1000 mg Azithromycin (AZ) and 620 mg of Chloroquine (CQ) base (4 combination tablets of AZCQ with individual strength of 250 mg/155 mg), by mouth once daily for 3 days (Days 0, 1, 2) per treatment. There were a total of 3 treatments at 4-8 week intervals.	The participants received sulfadoxine-pyrimethamine (SP) (Fansidar) treatment course: 1500 mg sulfadoxine and 75 mg pyrimethamine (3 fixed tablets of SP strength at 500 mg/25 mg), single oral dose on Day 0 of each treatment. There were a total of 3 treatments at 4-8 week intervals.
Measure Participants	1445	1445
Number (95% Confidence Interval) [Percentage of participants]	0.48 0%	1.25 0.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azithromycin + Chloroquine, Sulfadoxine + Pyrimethamine
	Comments	The 2-sided P-value tests the null hypothesis that the relative risk equals 1 (treatment group equality) versus not equal 1.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0332
	Comments	Mantel-Haenszel estimate of the common relative risk is presented, adjusting for randomization strata. A relative risk less than 1 favors Azithromycin + Chloroquine treatment group (reduction in risk for the endpoint).
	Method	Mantel Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.39
	Confidence Interval	(2-Sided) 95%; 0.16 to 0.93
	Parameter Dispersion	Type: Standard Deviation; Value: 0.4439
	Estimation Comments	The estimated risk ratio is presented along with its standard error (SE), with the SE on the log(e) scale.

28. Secondary Outcome

Title	Percentage of Participants With Pre-eclampsia From Week 20 to Delivery
Description	Pre-eclampsia was diagnosed as systolic blood pressure of at least 140 mmHg and/or diastolic blood pressure of at least 90 mmHg on two separate readings taken at least 4 hours apart and proteinuria at least 300 mg protein in a 24 hour urine collection.
Time Frame	From Week 20 to approximately 40 weeks of gestational age

Outcome Measure Data

Analysis Population Description

ITT set was used which consisted of participants who were randomized, received at least one dose of study medication (Day 0 at Visit 1 is considered the first dose of study medication), and who had a single fetus. N= Number of participants with available data.

Arm/Group Title	Azithromycin + Chloroquine	Sulfadoxine + Pyrimethamine
Arm/Group Description	The participants received 1000 mg Azithromycin (AZ) and 620 mg of Chloroquine (CQ) base (4 combination tablets of AZCQ with individual strength of 250 mg/155 mg), by mouth once daily for 3 days (Days 0, 1, 2) per treatment. There were a total of 3 treatments at 4-8 week intervals.	The participants received sulfadoxine-pyrimethamine (SP) (Fansidar) treatment course: 1500 mg sulfadoxine and 75 mg pyrimethamine (3 fixed tablets of SP strength at 500 mg/25 mg), single oral dose on Day 0 of each treatment. There were a total of 3 treatments at 4-8 week intervals.
Measure Participants	1440	1443
Number (95% Confidence Interval) [Percentage of participants]	0.63 0%	1.04 0.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azithromycin + Chloroquine, Sulfadoxine + Pyrimethamine
	Comments	The 2-sided P-value tests the null hypothesis that the relative risk equals 1 (treatment group equality) versus not equal 1.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2321
	Comments	Mantel-Haenszel estimate of the common relative risk is presented, adjusting for randomization strata. A relative risk less than 1 favors Azithromycin + Chloroquine treatment group (reduction in risk for the endpoint).
	Method	Mantel Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.61
	Confidence Interval	(2-Sided) 95%; 0.27 to 1.38
	Parameter Dispersion	Type: Standard Deviation; Value: 0.4195
	Estimation Comments	The estimated risk ratio is presented along with its standard error (SE), with the SE on the log(e) scale.

29. Secondary Outcome

Title	Nasopharyngeal Swabs Positive for Macrolide Resistant Streptococcus Pneumoniae
Description	This outcome measure evaluated the Streptococcus pneumoniae sensitivity against macrolide antibiotics.
Time Frame	Visits 6 and 7

Outcome Measure Data

Analysis Population Description

ITT set was used which consisted of participants who were randomized, received at least one dose of study medication (Day 0 at Visit 1 is considered the first dose of study medication), and who had a single fetus. N=Number of participant with nasopharyngeal swabs isolating Streptococcus pneumoniae at the specified visit.

Arm/Group Title	Azithromycin + Chloroquine	Sulfadoxine + Pyrimethamine
Arm/Group Description	The participants received 1000 mg Azithromycin (AZ) and 620 mg of Chloroquine (CQ) base (4 combination tablets of AZCQ with individual strength of 250 mg/155 mg), by mouth once daily for 3 days (Days 0, 1, 2) per treatment. There were a total of 3 treatments at 4-8 week intervals.	The participants received sulfadoxine-pyrimethamine (SP) (Fansidar) treatment course: 1500 mg sulfadoxine and 75 mg pyrimethamine (3 fixed tablets of SP strength at 500 mg/25 mg), single oral dose on Day 0 of each treatment. There were a total of 3 treatments at 4-8 week intervals.
Measure Participants	1445	1445
Visit 6 (N = 8 and 17 respectively)	0 0%	11.76 0.8%
Visit 7 (N = 16 and 11 respectively)	0 0%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azithromycin + Chloroquine, Sulfadoxine + Pyrimethamine
	Comments	Statistical analysis for Visit 6 presented above.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	1.0000
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-11.76
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azithromycin + Chloroquine, Sulfadoxine + Pyrimethamine
	Comments	Statistical analysis for Visit 7 presented above.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	1.0000
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

30. Secondary Outcome

Title	Nasopharyngeal Swabs Positive for Penicillin Resistant Streptococcus Pneumoniae
Description	This outcome measure evaluated the Streptococcus pneumoniae sensitivity against penicillin antibiotics.
Time Frame	Visits 6 and 7

Outcome Measure Data

Analysis Population Description

ITT set was used which consisted of participants who were randomized, received at least one dose of study medication (Day 0 at Visit 1 is considered the first dose of study medication), and who had a single fetus. N=Number of participant with nasopharyngeal swabs isolating Streptococcus pneumoniae at the specified visit.

Arm/Group Title	Azithromycin + Chloroquine	Sulfadoxine + Pyrimethamine
Arm/Group Description	The participants received 1000 mg Azithromycin (AZ) and 620 mg of Chloroquine (CQ) base (4 combination tablets of AZCQ with individual strength of 250 mg/155 mg), by mouth once daily for 3 days (Days 0, 1, 2) per treatment. There were a total of 3 treatments at 4-8 week intervals.	The participants received sulfadoxine-pyrimethamine (SP) (Fansidar) treatment course: 1500 mg sulfadoxine and 75 mg pyrimethamine (3 fixed tablets of SP strength at 500 mg/25 mg), single oral dose on Day 0 of each treatment. There were a total of 3 treatments at 4-8 week intervals.
Measure Participants	1445	1445
Visit 6 (N = 8 and 17 respectively)	0 0%	0 0%
Visit 7 (N = 16 and 11 respectively)	0 0%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azithromycin + Chloroquine, Sulfadoxine + Pyrimethamine
	Comments	Statistical analysis for Visit 6 presented above.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	1.0000
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Azithromycin + Chloroquine, Sulfadoxine + Pyrimethamine
	Comments	Statistical analysis for Visit 7 presented above.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	1.0000
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Up to Visit 7 (6 months post last dose). Includes data up to 35 days after last dose of study drug for mothers (treatment emergent), and includes all data for neonates.
Adverse Event Reporting Description	The same event may appear as both an AE and a SAE. However, what is presented are distinct events. Some events are seen only in neonates (e.g neonatal malformation/anomalies, LBW etc.) and are not expected in mothers and vice versa. Such events are designated as 'zero' in the respective 'familial status- neonate/mother' in the below table.
Arm/Group Title	Mother (Azithromycin + Chloroquine)		Mother (Sulfadoxine + Pyrimethamine)		Neonate (Azithromycin + Chloroquine)		Neonate (Sulfadoxine + Pyrimethamine)
Arm/Group Description	The participants received 1000 mg Azithromycin (AZ) and 620 mg of Chloroquine (CQ) base (4 combination tablets of AZCQ with individual strength of 250 mg/155 mg), by mouth once daily for 3 days (Days 0, 1, 2) per treatment. There were a total of 3 treatments at 4-8 week intervals.		The participants received sulfadoxine-pyrimethamine (SP) (Fansidar) treatment course: 1500 mg sulfadoxine and 75 mg pyrimethamine (3 fixed tablets of SP strength at 500 mg/25 mg), single oral dose on Day 0 of each treatment. There were a total of 3 treatments at 4-8 week intervals.		Live births of participants who received 1000 mg Azithromycin (AZ) and 620 mg of Chloroquine (CQ) base (4 combination tablets of AZCQ with individual strength of 250 mg/155 mg), by mouth once daily for 3 days (Days 0, 1, 2) per treatment. There were a total of 3 treatments at 4-8 week intervals.		Live births of participants who received sulfadoxine-pyrimethamine (SP) (Fansidar) treatment course: 1500 mg sulfadoxine and 75 mg pyrimethamine (3 fixed tablets of SP strength at 500 mg/25 mg), single oral dose on Day 0 of each treatment. There were a total of 3 treatments at 4-8 week intervals.
All Cause Mortality
	Mother (Azithromycin + Chloroquine)		Mother (Sulfadoxine + Pyrimethamine)		Neonate (Azithromycin + Chloroquine)		Neonate (Sulfadoxine + Pyrimethamine)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Mother (Azithromycin + Chloroquine)		Mother (Sulfadoxine + Pyrimethamine)		Neonate (Azithromycin + Chloroquine)		Neonate (Sulfadoxine + Pyrimethamine)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	65/1446 (4.5%)		42/1445 (2.9%)		101/1149 (8.8%)		104/1196 (8.7%)
Blood and lymphatic system disorders
Anaemia	1/1446 (0.1%)		0/1445 (0%)		3/1149 (0.3%)		2/1196 (0.2%)
Haemorrhagic disease of newborn	0/1446 (0%)		0/1445 (0%)		0/1149 (0%)		1/1196 (0.1%)
Cardiac disorders
Tricuspid valve disease	0/1446 (0%)		0/1445 (0%)		1/1149 (0.1%)		0/1196 (0%)
Tricuspid valve incompetence	0/1446 (0%)		0/1445 (0%)		1/1149 (0.1%)		0/1196 (0%)
Congenital, familial and genetic disorders
Anal atresia	0/1446 (0%)		0/1445 (0%)		1/1149 (0.1%)		1/1196 (0.1%)
Cerebellar hypoplasia	0/1446 (0%)		0/1445 (0%)		1/1149 (0.1%)		0/1196 (0%)
Congenital hand malformation	0/1446 (0%)		0/1445 (0%)		1/1149 (0.1%)		0/1196 (0%)
Congenital malaria	0/1446 (0%)		0/1445 (0%)		3/1149 (0.3%)		2/1196 (0.2%)
Congenital umbilical hernia	0/1446 (0%)		0/1445 (0%)		2/1149 (0.2%)		2/1196 (0.2%)
Cystic lymphangioma	0/1446 (0%)		0/1445 (0%)		0/1149 (0%)		1/1196 (0.1%)
Dysmorphism	0/1446 (0%)		0/1445 (0%)		1/1149 (0.1%)		0/1196 (0%)
Exomphalos	0/1446 (0%)		0/1445 (0%)		1/1149 (0.1%)		0/1196 (0%)
Heart disease congenital	0/1446 (0%)		0/1445 (0%)		0/1149 (0%)		1/1196 (0.1%)
Hypospadias	0/1446 (0%)		0/1445 (0%)		2/1149 (0.2%)		1/1196 (0.1%)
Microgenia	0/1446 (0%)		0/1445 (0%)		1/1149 (0.1%)		0/1196 (0%)
Polydactyly	0/1446 (0%)		0/1445 (0%)		16/1149 (1.4%)		21/1196 (1.8%)
Talipes	0/1446 (0%)		0/1445 (0%)		0/1149 (0%)		1/1196 (0.1%)
Gastrointestinal disorders
Diarrhoea	1/1446 (0.1%)		0/1445 (0%)		0/1149 (0%)		0/1196 (0%)
Enterocolitis	0/1446 (0%)		0/1445 (0%)		1/1149 (0.1%)		0/1196 (0%)
Gastritis	0/1446 (0%)		1/1445 (0.1%)		0/1149 (0%)		0/1196 (0%)
Necrotising colitis	0/1446 (0%)		0/1445 (0%)		0/1149 (0%)		1/1196 (0.1%)
Rectourethral fistula	0/1446 (0%)		0/1445 (0%)		1/1149 (0.1%)		0/1196 (0%)
Umbilical hernia	0/1446 (0%)		0/1445 (0%)		2/1149 (0.2%)		3/1196 (0.3%)
Vomiting	3/1446 (0.2%)		0/1445 (0%)		0/1149 (0%)		0/1196 (0%)
General disorders
Asthenia	1/1446 (0.1%)		0/1445 (0%)		0/1149 (0%)		0/1196 (0%)
Death neonatal	0/1446 (0%)		0/1445 (0%)		0/1149 (0%)		2/1196 (0.2%)
Pyrexia	0/1446 (0%)		0/1445 (0%)		1/1149 (0.1%)		0/1196 (0%)
Hepatobiliary disorders
Hepatitis cholestatic	1/1446 (0.1%)		0/1445 (0%)		0/1149 (0%)		0/1196 (0%)
Jaundice	0/1446 (0%)		0/1445 (0%)		1/1149 (0.1%)		0/1196 (0%)
Infections and infestations
Arthritis bacterial	0/1446 (0%)		0/1445 (0%)		0/1149 (0%)		1/1196 (0.1%)
Bartholin's abscess	1/1446 (0.1%)		0/1445 (0%)		0/1149 (0%)		0/1196 (0%)
Bronchiolitis	0/1446 (0%)		0/1445 (0%)		1/1149 (0.1%)		0/1196 (0%)
Bronchopneumonia	0/1446 (0%)		0/1445 (0%)		0/1149 (0%)		2/1196 (0.2%)
Cellulitis	0/1446 (0%)		1/1445 (0.1%)		0/1149 (0%)		0/1196 (0%)
Encephalitis	0/1446 (0%)		0/1445 (0%)		1/1149 (0.1%)		0/1196 (0%)
Gastroenteritis	0/1446 (0%)		0/1445 (0%)		0/1149 (0%)		2/1196 (0.2%)
Herpes zoster	0/1446 (0%)		0/1445 (0%)		0/1149 (0%)		1/1196 (0.1%)
Malaria	2/1446 (0.1%)		9/1445 (0.6%)		2/1149 (0.2%)		3/1196 (0.3%)
Meningitis	1/1446 (0.1%)		0/1445 (0%)		1/1149 (0.1%)		1/1196 (0.1%)
Neonatal infection	0/1446 (0%)		0/1445 (0%)		5/1149 (0.4%)		4/1196 (0.3%)
Pneumonia	1/1446 (0.1%)		1/1445 (0.1%)		9/1149 (0.8%)		10/1196 (0.8%)
Pyelonephritis acute	1/1446 (0.1%)		0/1445 (0%)		0/1149 (0%)		0/1196 (0%)
Sepsis	1/1446 (0.1%)		0/1445 (0%)		2/1149 (0.2%)		3/1196 (0.3%)
Sepsis neonatal	0/1446 (0%)		0/1445 (0%)		11/1149 (1%)		13/1196 (1.1%)
Skin bacterial infection	0/1446 (0%)		0/1445 (0%)		0/1149 (0%)		1/1196 (0.1%)
Upper respiratory tract infection	0/1446 (0%)		0/1445 (0%)		1/1149 (0.1%)		0/1196 (0%)
Urinary tract infection	0/1446 (0%)		2/1445 (0.1%)		0/1149 (0%)		0/1196 (0%)
Varicella	1/1446 (0.1%)		0/1445 (0%)		0/1149 (0%)		0/1196 (0%)
Viral rash	0/1446 (0%)		0/1445 (0%)		1/1149 (0.1%)		0/1196 (0%)
Injury, poisoning and procedural complications
Uterine rupture	1/1446 (0.1%)		0/1445 (0%)		0/1149 (0%)		0/1196 (0%)
Investigations
Apgar score low	0/1446 (0%)		0/1445 (0%)		1/1149 (0.1%)		1/1196 (0.1%)
HIV test positive	0/1446 (0%)		0/1445 (0%)		1/1149 (0.1%)		0/1196 (0%)
Metabolism and nutrition disorders
Dehydration	0/1446 (0%)		0/1445 (0%)		1/1149 (0.1%)		0/1196 (0%)
Hypoglycaemia	0/1446 (0%)		0/1445 (0%)		1/1149 (0.1%)		1/1196 (0.1%)
Malnutrition	0/1446 (0%)		0/1445 (0%)		1/1149 (0.1%)		0/1196 (0%)
Metabolic disorder	0/1446 (0%)		0/1445 (0%)		0/1149 (0%)		1/1196 (0.1%)
Musculoskeletal and connective tissue disorders
Foot deformity	0/1446 (0%)		0/1445 (0%)		1/1149 (0.1%)		0/1196 (0%)
Nervous system disorders
Convulsion	0/1446 (0%)		0/1445 (0%)		1/1149 (0.1%)		0/1196 (0%)
Dizziness	3/1446 (0.2%)		0/1445 (0%)		0/1149 (0%)		0/1196 (0%)
Epilepsy	0/1446 (0%)		0/1445 (0%)		1/1149 (0.1%)		0/1196 (0%)
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous	3/1446 (0.2%)		2/1445 (0.1%)		0/1149 (0%)		0/1196 (0%)
Abortion spontaneous complete	2/1446 (0.1%)		0/1445 (0%)		0/1149 (0%)		0/1196 (0%)
Abortion threatened	4/1446 (0.3%)		0/1445 (0%)		0/1149 (0%)		0/1196 (0%)
Eclampsia	1/1446 (0.1%)		0/1445 (0%)		0/1149 (0%)		0/1196 (0%)
Foetal death	3/1446 (0.2%)		0/1445 (0%)		0/1149 (0%)		0/1196 (0%)
Foetal distress syndrome	1/1446 (0.1%)		0/1445 (0%)		0/1149 (0%)		0/1196 (0%)
Gestational hypertension	2/1446 (0.1%)		0/1445 (0%)		0/1149 (0%)		0/1196 (0%)
HELLP syndrome	1/1446 (0.1%)		0/1445 (0%)		0/1149 (0%)		0/1196 (0%)
Haemorrhage in pregnancy	7/1446 (0.5%)		1/1445 (0.1%)		0/1149 (0%)		0/1196 (0%)
Imminent abortion	1/1446 (0.1%)		0/1445 (0%)		0/1149 (0%)		0/1196 (0%)
Jaundice neonatal	0/1446 (0%)		0/1445 (0%)		3/1149 (0.3%)		0/1196 (0%)
Low birth weight baby	0/1446 (0%)		0/1445 (0%)		9/1149 (0.8%)		10/1196 (0.8%)
Neonatal disorder	0/1446 (0%)		0/1445 (0%)		1/1149 (0.1%)		0/1196 (0%)
Obstructed labour	1/1446 (0.1%)		0/1445 (0%)		0/1149 (0%)		0/1196 (0%)
Placental disorder	0/1446 (0%)		0/1445 (0%)		1/1149 (0.1%)		0/1196 (0%)
Placental infarction	1/1446 (0.1%)		0/1445 (0%)		0/1149 (0%)		0/1196 (0%)
Postpartum haemorrhage	2/1446 (0.1%)		0/1445 (0%)		0/1149 (0%)		0/1196 (0%)
Pre-eclampsia	3/1446 (0.2%)		5/1445 (0.3%)		0/1149 (0%)		0/1196 (0%)
Premature baby	0/1446 (0%)		0/1445 (0%)		17/1149 (1.5%)		12/1196 (1%)
Premature delivery	7/1446 (0.5%)		5/1445 (0.3%)		0/1149 (0%)		0/1196 (0%)
Premature labour	4/1446 (0.3%)		4/1445 (0.3%)		0/1149 (0%)		0/1196 (0%)
Premature rupture of membranes	1/1446 (0.1%)		2/1445 (0.1%)		0/1149 (0%)		0/1196 (0%)
Preterm premature rupture of membranes	4/1446 (0.3%)		3/1445 (0.2%)		0/1149 (0%)		0/1196 (0%)
Stillbirth	5/1446 (0.3%)		7/1445 (0.5%)		0/1149 (0%)		0/1196 (0%)
Threatened labour	3/1446 (0.2%)		3/1445 (0.2%)		0/1149 (0%)		0/1196 (0%)
Umbilical cord around neck	0/1446 (0%)		0/1445 (0%)		0/1149 (0%)		2/1196 (0.2%)
Renal and urinary disorders
Calculus urinary	0/1446 (0%)		1/1445 (0.1%)		0/1149 (0%)		0/1196 (0%)
Renal vessel disorder	0/1446 (0%)		1/1445 (0.1%)		0/1149 (0%)		0/1196 (0%)
Reproductive system and breast disorders
Acquired phimosis	0/1446 (0%)		0/1445 (0%)		1/1149 (0.1%)		0/1196 (0%)
Respiratory, thoracic and mediastinal disorders
Asthma	1/1446 (0.1%)		1/1445 (0.1%)		0/1149 (0%)		1/1196 (0.1%)
Neonatal asphyxia	0/1446 (0%)		0/1445 (0%)		6/1149 (0.5%)		9/1196 (0.8%)
Neonatal aspiration	0/1446 (0%)		0/1445 (0%)		1/1149 (0.1%)		5/1196 (0.4%)
Neonatal respiratory distress syndrome	0/1446 (0%)		0/1445 (0%)		2/1149 (0.2%)		4/1196 (0.3%)
Obstructive airways disorder	0/1446 (0%)		0/1445 (0%)		1/1149 (0.1%)		0/1196 (0%)
Pneumonia aspiration	0/1446 (0%)		0/1445 (0%)		1/1149 (0.1%)		3/1196 (0.3%)
Respiratory arrest	0/1446 (0%)		0/1445 (0%)		1/1149 (0.1%)		0/1196 (0%)
Respiratory distress	0/1446 (0%)		0/1445 (0%)		3/1149 (0.3%)		1/1196 (0.1%)
Vascular disorders
Deep vein thrombosis	1/1446 (0.1%)		0/1445 (0%)		0/1149 (0%)		0/1196 (0%)
Orthostatic hypotension	1/1446 (0.1%)		0/1445 (0%)		0/1149 (0%)		0/1196 (0%)
Other (Not Including Serious) Adverse Events
	Mother (Azithromycin + Chloroquine)		Mother (Sulfadoxine + Pyrimethamine)		Neonate (Azithromycin + Chloroquine)		Neonate (Sulfadoxine + Pyrimethamine)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1177/1446 (81.4%)		888/1445 (61.5%)		301/1149 (26.2%)		326/1196 (27.3%)
Blood and lymphatic system disorders
Anaemia	205/1446 (14.2%)		192/1445 (13.3%)		21/1149 (1.8%)		14/1196 (1.2%)
Eye disorders
Vision blurred	145/1446 (10%)		1/1445 (0.1%)		0/1149 (0%)		0/1196 (0%)
Gastrointestinal disorders
Abdominal discomfort	123/1446 (8.5%)		50/1445 (3.5%)		0/1149 (0%)		0/1196 (0%)
Abdominal pain	120/1446 (8.3%)		36/1445 (2.5%)		0/1149 (0%)		0/1196 (0%)
Abdominal pain lower	50/1446 (3.5%)		45/1445 (3.1%)		0/1149 (0%)		0/1196 (0%)
Diarrhoea	205/1446 (14.2%)		14/1445 (1%)		0/1149 (0%)		0/1196 (0%)
Dyspepsia	8/1446 (0.6%)		15/1445 (1%)		0/1149 (0%)		0/1196 (0%)
Gastritis	23/1446 (1.6%)		7/1445 (0.5%)		0/1149 (0%)		0/1196 (0%)
Nausea	216/1446 (14.9%)		58/1445 (4%)		0/1149 (0%)		0/1196 (0%)
Vomiting	650/1446 (45%)		96/1445 (6.6%)		0/1149 (0%)		0/1196 (0%)
General disorders
Asthenia	239/1446 (16.5%)		40/1445 (2.8%)		0/1149 (0%)		0/1196 (0%)
Fatigue	81/1446 (5.6%)		22/1445 (1.5%)		0/1149 (0%)		0/1196 (0%)
Pyrexia	10/1446 (0.7%)		26/1445 (1.8%)		40/1149 (3.5%)		28/1196 (2.3%)
Infections and infestations
Conjunctivitis	0/1446 (0%)		0/1445 (0%)		15/1149 (1.3%)		10/1196 (0.8%)
Gastroenteritis	44/1446 (3%)		21/1445 (1.5%)		48/1149 (4.2%)		37/1196 (3.1%)
Infection parasitic	14/1446 (1%)		18/1445 (1.2%)		0/1149 (0%)		0/1196 (0%)
Malaria	49/1446 (3.4%)		121/1445 (8.4%)		37/1149 (3.2%)		37/1196 (3.1%)
Pneumonia	0/1446 (0%)		0/1445 (0%)		34/1149 (3%)		25/1196 (2.1%)
Sepsis	0/1446 (0%)		0/1445 (0%)		18/1149 (1.6%)		9/1196 (0.8%)
Sepsis neonatal	0/1446 (0%)		0/1445 (0%)		21/1149 (1.8%)		21/1196 (1.8%)
Trichomoniasis	58/1446 (4%)		55/1445 (3.8%)		0/1149 (0%)		0/1196 (0%)
Upper respiratory tract infection	127/1446 (8.8%)		153/1445 (10.6%)		125/1149 (10.9%)		116/1196 (9.7%)
Urinary tract infection	105/1446 (7.3%)		115/1445 (8%)		0/1149 (0%)		0/1196 (0%)
Vulvovaginal candidiasis	75/1446 (5.2%)		60/1445 (4.2%)		0/1149 (0%)		0/1196 (0%)
Injury, poisoning and procedural complications
Perineal injury	19/1446 (1.3%)		20/1445 (1.4%)		0/1149 (0%)		0/1196 (0%)
Investigations
White blood cells urine positive	149/1446 (10.3%)		162/1445 (11.2%)		0/1149 (0%)		0/1196 (0%)
Metabolism and nutrition disorders
Decreased appetite	44/1446 (3%)		11/1445 (0.8%)		0/1149 (0%)		0/1196 (0%)
Musculoskeletal and connective tissue disorders
Back pain	33/1446 (2.3%)		29/1445 (2%)		0/1149 (0%)		0/1196 (0%)
Nervous system disorders
Dizziness	460/1446 (31.8%)		84/1445 (5.8%)		0/1149 (0%)		0/1196 (0%)
Headache	300/1446 (20.7%)		219/1445 (15.2%)		0/1149 (0%)		0/1196 (0%)
Somnolence	38/1446 (2.6%)		0/1445 (0%)		0/1149 (0%)		0/1196 (0%)
Pregnancy, puerperium and perinatal conditions
Low birth weight baby	0/1446 (0%)		0/1445 (0%)		29/1149 (2.5%)		39/1196 (3.3%)
Premature baby	0/1446 (0%)		0/1445 (0%)		28/1149 (2.4%)		28/1196 (2.3%)
Respiratory, thoracic and mediastinal disorders
Cough	15/1446 (1%)		10/1445 (0.7%)		0/1149 (0%)		0/1196 (0%)
Skin and subcutaneous tissue disorders
Pruritus	46/1446 (3.2%)		23/1445 (1.6%)		0/1149 (0%)		0/1196 (0%)
Pruritus generalised	22/1446 (1.5%)		8/1445 (0.6%)		0/1149 (0%)		0/1196 (0%)

Limitations/Caveats

This program was terminated by Pfizer based on the results of the pre-planned interim analysis for this pivotal study. The interim analysis showed no benefit of the study drug (AZCQ) compared to standard of care (SP).

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.