Chloroquine for Malaria in Pregnancy

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT01443130
• Collaborator: (none)
• Enrollment: 900
• Location: 1
• Arms: 3
• Duration (Months): 35
• Patients Per Site Per Month: 25.7

Study Details

Study Description

Brief Summary

The purpose of this study is to test prevention strategies for pregnancy-related malaria. Researchers will compare different malaria treatments and treatment schedules which include chloroquine therapy (weekly doses versus being dosed twice during pregnancy for 3 days each time) to the standard practice of preventive treatment intervals in pregnancy (with the drug sulfadoxine-pyrimethamine given twice during pregnancy). Participants will include 900 pregnant women, who will be assigned to one of three treatment groups. Blood samples will be collected at every visit before birth and any time the participant is ill to determine if malaria is present. Pregnant women will be monitored during pregnancy and newborns will be assessed at birth and followed until about 14 weeks. Participant involvement in the study is expected to last about 12 months.

Condition or Disease	Intervention/Treatment	Phase
Malaria	Drug: Chloroquine; Drug: Sulfadoxine-pyrimethamine	Phase 3

Detailed Description

In areas of high malaria endemicity, typical of much of sub-Saharan Africa, despite having achieved semi-immunity to malaria in adulthood, women become vulnerable to malaria infection during pregnancy, especially during their first or second pregnancy. They have increased rates of infection in the peripheral blood and high concentrations of parasites can be found in the placenta. On histological examination, mature asexual parasites, forms that are not usually detected in the peripheral blood, accumulate in the placenta. Pregnancy-specific variant surface antigens are responsible for the increased vulnerability of pregnant women to malaria because they are unrecognized by the immune systems of women who encounter them for the first time in their first pregnancy. In subsequent pregnancies, women develop immunity to these parasite surface antigens and the parasites are cleared by the host response. Plasmodium (P) falciparum infection during pregnancy has important health consequences for both pregnant women and their newborns. Adverse outcomes of pregnancy-associated malaria that have been documented in Malawi include maternal anemia, low birth weight (LBW), and increased infant mortality. The primary objective of the study is to compare weekly chloroquine prophylaxis and chloroquine intermittent preventative therapy (IPT) for malaria in pregnancy (IPTp) to the standard practice [IPTp with sulfadoxine-pyrimethamine (SP)] with respect to prevention of placental malaria. The secondary objectives are: to compare weekly chloroquine prophylaxis and chloroquine IPTp to the standard practice (IPTp with SP) with respect to prevention of malaria during pregnancy; to compare weekly chloroquine prophylaxis and chloroquine IPTp to the standard practice (IPTp with SP) with respect to prevention of the adverse maternal and newborn effects of pregnancy-associated malaria. The exploratory objective identify the vulnerable periods during pregnancy when malaria infection is more likely to cause placental infection, maternal anemia, and low infant birth weight. This is a randomized controlled trial to compare chloroquine as IPT or chloroquine as chemoprophylaxis to IPTp with SP. Women will be randomized after Screening and enrollment, and they begin the assigned treatment between Week 20 and Week 28 gestation. Specimens will be collected at every prenatal visit and any time the participant is ill to determine if malaria is present. Pregnant women will be monitored during pregnancy, and newborns will be assessed at birth and followed until they are approximately 14 weeks of age. Participants will be randomized to one of the following regimens: Chloroquine approximately 1,500 mg base over 3 days, twice during pregnancy (2 tablets on Day 0, 2 tablets on Day 1, 1 tablet on Day 2); Chloroquine base 600 mg (2 tablets) loading dose followed by 300 mg (1 tablet) orally once per week until delivery; SP 1500 mg/75 mg twice during pregnancy.

Study Design

• Study Type: Interventional
• Actual Enrollment: 900 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: A Randomized, Controlled Clinical Trial of Chloroquine as Chemoprophylaxis Versus Intermittent Preventive Therapy to Prevent Malaria in Pregnancy in Malawi
• Study Start Date: Feb 1, 2012
• Actual Primary Completion Date: Oct 1, 2014
• Actual Study Completion Date: Jan 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Chloroquine IPT 300 subjects to receive a therapeutic dose of chloroquine (1,500 mg given over 3 days, 2 tablets on Day 0, 2 tablets on Day 1, 1 tablet on Day 2) will be administered twice during pregnancy at 20-28 weeks and at 28-34 weeks.	Drug: Chloroquine; Chloroquine tablets contain 300 mg chloroquine base per tablet. Dosages: Chloroquine 1,500 mg base over 3 days twice during pregnancy or Chloroquine 600 mg loading dose followed by 300 mg orally once per week. Intermittant preventative treatment in pregnancy (IPTp) doses will be administered between weeks 20-28 and weeks 28-34 gestation, 4 weeks apart. Participants randomized to IPTp with chloroquine will require their second and third doses of chloroquine after the initial dose given in the clinic and those assigned to chloroquine chemoprophylaxis will require weekly doses.
Experimental: Chloroquine Prophylaxis 300 subjects to receive a loading dose of chloroquine (base) 600 mg (2 tablets) at first administration followed by 300 mg of chloroquine base (1 tablet) every week.	Drug: Chloroquine; Chloroquine tablets contain 300 mg chloroquine base per tablet. Dosages: Chloroquine 1,500 mg base over 3 days twice during pregnancy or Chloroquine 600 mg loading dose followed by 300 mg orally once per week. Intermittant preventative treatment in pregnancy (IPTp) doses will be administered between weeks 20-28 and weeks 28-34 gestation, 4 weeks apart. Participants randomized to IPTp with chloroquine will require their second and third doses of chloroquine after the initial dose given in the clinic and those assigned to chloroquine chemoprophylaxis will require weekly doses.
Active Comparator: SP IPT 300 subjects to receive a therapeutic dose of sulfadoxine-pyrimethamine (SP), (1500 mg sulfadoxine and 75 mg pyrimethamine (3 tablets)) administered twice during pregnancy at 20-28 weeks and at 28-34 weeks.	Drug: Sulfadoxine-pyrimethamine; Sulfadoxine-pyrimethamine 3 tablets (1,500 mg sulfadoxine and 75 mg pyrimethamine) twice during pregnancy. Intermittant preventive treatment in pregnancy (IPTp) doses will be administered between weeks 20-28 and weeks 28-34, 4 weeks apart.

Outcome Measures

Primary Outcome Measures

1. Incidence of Placental Malaria Infection Based on Histology [At delivery: Approximately 12-36 weeks after enrollment]

   The placenta was collected at the time of delivery for examination by histology to determine malaria infection. Malaria infection was concluded if histology identified parasites or malaria pigment in the placental tissue.

Secondary Outcome Measures

1. Incidence of Placental Malaria by Placental Impression Smear [At delivery: Approximately 12-36 weeks after enrollment]

   Maternal participants were followed to outcome of the pregnancy. The outcome measure provides the incidence of malaria infection in the placenta based on diagnosis by positive placental impression smear results.

2. Incidence of Maternal Anemia (Hemoglobin < 10 Grams/Deciliter) [From enrollment until delivery, approximately 12-36 weeks]

   Maternal participants were followed to outcome of the pregnancy. The outcome measure provides the incidence of anemia among maternal participants during pregnancy . Anemia is defined as having a hemoglobin value less than 10 grams/deciliter (gm/dL).

3. Incidence of Maternal Severe Anemia (Hemoglobin < 7gm/dl) [From enrollment until delivery, approximately 12-36 weeks]

   Maternal participants were followed to outcome of the pregnancy. The outcome measure provides the incidence of severe anemia among maternal participants during pregnancy. Severe anemia is defined as having a hemoglobin value less than 7 gm/dl.

4. Incidence of Stillbirth [At delivery: Approximately 12-36 weeks after enrollment]

   Maternal participants were followed to outcome of the pregnancy. The outcome measure provides the incidence of participants' deliveries whose outcome was stillbirth, defined as an infant born without any signs of life at 28 weeks or greater of gestation.

5. Incidence of Miscarriage [At delivery: Approximately 12-36 weeks after enrollment]

   Maternal participants were followed to outcome of the pregnancy. The outcome measure provides the incidence of participants' deliveries whose outcome was miscarriage, defined as an infant delivered without any signs of life at less than 28 weeks of gestation.

6. Incidence of Preterm Delivery [At delivery: Approximately 12-36 weeks after enrollment]

   Maternal participants were followed to outcome of the pregnancy. The outcome measure provides the incidence of participants' deliveries whose outcome was preterm delivery, defined as delivery less than 37 weeks of gestation. The outcome of the delivery was not considered, and could have been live birth, stillbirth, or miscarriage.

7. Infant Mortality Rate to 14 Weeks of Age [For 14 weeks after delivery.]

   Infants were followed from the time of delivery until 14 weeks of age. This outcome measure provides the incidence of infants who died within 14 weeks of delivery.

8. Incidence of Low Birth Weight (LBW) (Birthweight < 2500 Grams) [At delivery: Approximately 12-36 weeks after enrollment]

   Maternal participants were followed to outcome of the pregnancy. The outcome measure provides the incidence of infants whose birthweight was less than 2500 grams.

9. Incidence of Intrauterine Growth Restriction (IUGR) [At delivery: Approximately 12-36 weeks after enrollment]

   Infants were followed from the time of delivery until 14 weeks of age. This outcome measure provides the incidence of infants with IUGR at delivery. IUGR is defined as weight below the 10th percentile for gestational age based on the World Health Organization (WHO) fetal growth curve. This classification is supported by literature resulting from the INTERGROWTH-21st Project; José Villar.

10. Incidence of Active Placental Malaria Infection [At delivery: Approximately 12-36 weeks after enrollment]

    Maternal participants were followed to outcome of the pregnancy. This outcome measure provides the number of placental malaria infections in maternal subjects diagnosed by the presence of parasites and/or pigment on histological section or molecular evidence of infection (PCR).

11. Incidence of Malaria Infection, All Species. [Enrollment to delivery (approximately 12-36 weeks)]

    Maternal participants were followed to outcome of the pregnancy. This outcome measure provides the number of malaria infection episodes measured by positive parasitemia in maternal subjects.

12. Incidence of Clinical Malaria, All Species [Enrollment to delivery (approximately 12-36 weeks)]

    Maternal participants were followed to outcome of the pregnancy. Clinical malaria is defined as malaria infection at any parasite density with associated symptoms including at least one of the following: objective fever measured at the clinic, history of fever in the past 48 hours or other symptoms in the last 48 hours including: headache, myalgia, vomiting, or weakness.

13. Incidence of Infection in the Fetal Circulation [At delivery: Approximately 12-36 weeks after enrollment]

    Maternal participants were followed to outcome of the pregnancy. This outcome measure provides the number of positive for malaria cord blood smear and cord PCR results in maternal subjects based on the results of the thick smear and PCR from the cord blood sample.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 99 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Women who present to the Ndirande Antenatal Clinic (ANC) and meet the following inclusion criteria will be enrolled in the study: -Before the end of 27th week of gestation -First or second pregnancy -Anticipate remaining in Blantyre until 14 weeks after delivery -Agree to deliver at the Ndirande Health Centre or Queen Elizabeth Central Hospital (QECH) -Provision of informed consent

Exclusion Criteria:

-Chronic use (>14 days) of any medication with antimalarial or antifolate activity -Human immunodeficiency virus (HIV) infection -Known high-risk pregnancy requiring regular supervision of an obstetrician -Allergy to any of the study drugs

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Blantyre Malaria Project - Queen Elizabeth Central Hospital	Blantryre	Blantyre	Malawi

Sponsors and Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT01443130
• Other Study ID Numbers: 09-0112; 4R01AI104702-04
• First Posted: Sep 29, 2011
• Last Update Posted: Dec 28, 2016
• Last Verified: May 1, 2015

• Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID): malaria,Malawi,pregnancy
• Additional relevant MeSH terms: Malaria; Chloroquine; Pyrimethamine; Sulfadoxine; Fanasil, pyrimethamine drug combination

Study Results

Participant Flow

Recruitment Details	Participants were pregnant women in their first or second pregnancy recruited during presentation at the Ndirande Antenatal Clinic (ANC) at the Ndirande Health Centre, enrolled between 22 February 2012 and 16 May 2014.
Pre-assignment Detail	The infants born to these participants were also enrolled in the study to be assessed at birth and followed to 14 weeks. The infants are reported here as separate arms of the study, grouped by the study product given to the mother.

Arm/Group Title	Maternal Chloroquine Prophylaxis	Maternal Chloroquine IPT	Maternal SP IPT	Infant Chloroquine Prophylaxis	Infant Chloroquine IPT	Infant SP IPT
Arm/Group Description	Maternal participants receive a loading dose of chloroquine (base) 600 mg (2 tablets) at first administration followed by 300 mg of chloroquine base (1 tablet) every week until delivery.	Maternal participants receive a therapeutic dose of chloroquine (1,500 mg given over 3 days, 2 tablets on Day 0, 2 tablets on Day 1, 1 tablet on Day 2) administered twice during pregnancy at 20-28 weeks and at 28-34 weeks.	Maternal participants receive a therapeutic dose of sulfadoxine-pyrimethamine (SP), (1500 mg sulfadoxine and 75 mg pyrimethamine (3 tablets)) administered twice during pregnancy at 20-28 weeks and at 28-34 weeks.	Infants born to maternal participants who received chloroquine prophylaxis.	Infants born to maternal participants who received chloroquine IPT.	Infants born to maternal participants who received SP IPT.
Period Title: Overall Study
STARTED	300	300	300	270	274	259
COMPLETED	232	231	223	231	230	225
NOT COMPLETED	68	69	77	39	44	34

Baseline Characteristics

Arm/Group Title	Maternal Chloroquine Prophylaxis	Maternal Chloroquine IPT	Maternal SP IPT	Infant Chloroquine Prophylaxis	Infant Chloroquine IPT	Infant SP IPT	Total
Arm/Group Description	Maternal participants receive a loading dose of chloroquine (base) 600 mg (2 tablets) at first administration followed by 300 mg of chloroquine base (1 tablet) every week until delivery.	Maternal participants receive a therapeutic dose of chloroquine (1,500 mg given over 3 days, 2 tablets on Day 0, 2 tablets on Day 1, 1 tablet on Day 2) administered twice during pregnancy at 20-28 weeks and at 28-34 weeks.	Maternal participants receive a therapeutic dose of sulfadoxine-pyrimethamine (SP), (1500 mg sulfadoxine and 75 mg pyrimethamine (3 tablets)) administered twice during pregnancy at 20-28 weeks and at 28-34 weeks.	Infants born to maternal participants who received chloroquine prophylaxis.	Infants born to maternal participants who received chloroquine IPT.	Infants born to maternal participants who received SP IPT.	Total of all reporting groups
Overall Participants	300	300	300	270	274	259	1703
Age (Count of Participants)
<=18 years	99 33%	81 27%	90 30%	270 100%	274 100%	259 100%	1073 63%
Between 18 and 65 years	201 67%	219 73%	210 70%	0 0%	0 0%	0 0%	630 37%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	20.40 (3.59)	20.67 (3.24)	20.44 (3.14)	0 (0)	0 (0)	0 (0)	20.50 (3.33)
Gender (Count of Participants)
Female	300 100%	300 100%	300 100%	133 49.3%	143 52.2%	136 52.5%	1312 77%
Male	0 0%	0 0%	0 0%	137 50.7%	131 47.8%	123 47.5%	391 23%
Region of Enrollment (participants) [Number]
Malawi	300 100%	300 100%	300 100%	270 100%	274 100%	259 100%	1703 100%

Outcome Measures

1. Primary Outcome

Title	Incidence of Placental Malaria Infection Based on Histology
Description	The placenta was collected at the time of delivery for examination by histology to determine malaria infection. Malaria infection was concluded if histology identified parasites or malaria pigment in the placental tissue.
Time Frame	At delivery: Approximately 12-36 weeks after enrollment

Outcome Measure Data

Analysis Population Description

All participants from whom the placental histopathology slides collected at the time of delivery were reviewed are included in the analysis.

Arm/Group Title	Maternal Chloroquine Prophylaxis	Maternal Chloroquine IPT	Maternal SP IPT
Arm/Group Description	Maternal participants receive a loading dose of chloroquine (base) 600 mg (2 tablets) at first administration followed by 300 mg of chloroquine base (1 tablet) every week until delivery.	Maternal participants receive a therapeutic dose of chloroquine (1,500 mg given over 3 days, 2 tablets on Day 0, 2 tablets on Day 1, 1 tablet on Day 2) administered twice during pregnancy at 20-28 weeks and at 28-34 weeks.	Maternal participants receive a therapeutic dose of sulfadoxine-pyrimethamine (SP), (1500 mg sulfadoxine and 75 mg pyrimethamine (3 tablets)) administered twice during pregnancy at 20-28 weeks and at 28-34 weeks.
Measure Participants	259	253	253
Number (97.5% Confidence Interval) [percentage of pregnancies]	11.58	15.42	15.42

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Maternal Chloroquine Prophylaxis, Maternal SP IPT
	Comments	The null hypothesis is the incidence of placental malaria infection based on histology is identical between subjects receiving maternal chloroquine prophylaxis vs. maternal SP IPT.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2441
	Comments	A Bonferroni correction was used due to multiple comparisons. Comparisons are statistically significant if the two-sided p-value is ≤ 0.05/2=0.025
	Method	Fisher Exact
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Maternal Chloroquine IPT, Maternal SP IPT
	Comments	The null hypothesis is the incidence of placental malaria infection based on histology is identical between subjects receiving maternal chloroquine IPT vs. maternal SP IPT.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	1.000
	Comments	A Bonferroni correction was used due to multiple comparisons. Comparisons are statistically significant if the two-sided p-value is ≤ 0.05/2=0.025
	Method	Fisher Exact
	Comments

2. Secondary Outcome

Title	Incidence of Placental Malaria by Placental Impression Smear
Description	Maternal participants were followed to outcome of the pregnancy. The outcome measure provides the incidence of malaria infection in the placenta based on diagnosis by positive placental impression smear results.
Time Frame	At delivery: Approximately 12-36 weeks after enrollment

Outcome Measure Data

Analysis Population Description

The analysis population includes all maternal participants whose pregnancies were followed to delivery and from whom a placenta was collected and an impression smear performed.

Arm/Group Title	Maternal Chloroquine Prophylaxis	Maternal Chloroquine IPT	Maternal SP IPT
Arm/Group Description	Maternal participants receive a loading dose of chloroquine (base) 600 mg (2 tablets) at first administration followed by 300 mg of chloroquine base (1 tablet) every week until delivery.	Maternal participants receive a therapeutic dose of chloroquine (1,500 mg given over 3 days, 2 tablets on Day 0, 2 tablets on Day 1, 1 tablet on Day 2) administered twice during pregnancy at 20-28 weeks and at 28-34 weeks.	Maternal participants receive a therapeutic dose of sulfadoxine-pyrimethamine (SP), (1500 mg sulfadoxine and 75 mg pyrimethamine (3 tablets)) administered twice during pregnancy at 20-28 weeks and at 28-34 weeks.
Measure Participants	259	254	253
Number (97.5% Confidence Interval) [percentage of placentas]	0	0	0.40

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Maternal Chloroquine Prophylaxis, Maternal SP IPT
	Comments	The null hypothesis is the incidence of malaria by placental impression smear is identical between subjects receiving maternal chloroquine prophylaxis vs. maternal SP IPT.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4941
	Comments	A Bonferroni correction was used due to multiple comparisons. Comparisons are statistically significant if the two-sided p-value is ≤ 0.05/2=0.025.
	Method	Fisher Exact
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Maternal Chloroquine IPT, Maternal SP IPT
	Comments	The null hypothesis is the incidence of malaria by placental impression smear is identical between subjects receiving maternal chloroquine IPT vs. maternal SP IPT.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4990
	Comments	A Bonferroni correction was used due to multiple comparisons. Comparisons are statistically significant if the two-sided p-value is ≤ 0.05/2=0.025.
	Method	Fisher Exact
	Comments

3. Secondary Outcome

Title	Incidence of Maternal Anemia (Hemoglobin < 10 Grams/Deciliter)
Description	Maternal participants were followed to outcome of the pregnancy. The outcome measure provides the incidence of anemia among maternal participants during pregnancy . Anemia is defined as having a hemoglobin value less than 10 grams/deciliter (gm/dL).
Time Frame	From enrollment until delivery, approximately 12-36 weeks

Outcome Measure Data

Analysis Population Description

The analysis population includes all maternal participants.

Arm/Group Title	Maternal Chloroquine Prophylaxis	Maternal Chloroquine IPT	Maternal SP IPT
Arm/Group Description	Maternal participants receive a loading dose of chloroquine (base) 600 mg (2 tablets) at first administration followed by 300 mg of chloroquine base (1 tablet) every week until delivery.	Maternal participants receive a therapeutic dose of chloroquine (1,500 mg given over 3 days, 2 tablets on Day 0, 2 tablets on Day 1, 1 tablet on Day 2) administered twice during pregnancy at 20-28 weeks and at 28-34 weeks.	Maternal participants receive a therapeutic dose of sulfadoxine-pyrimethamine (SP), (1500 mg sulfadoxine and 75 mg pyrimethamine (3 tablets)) administered twice during pregnancy at 20-28 weeks and at 28-34 weeks.
Measure Participants	300	300	300
Number (97.5% Confidence Interval) [percentage of maternal participants]	18.3 6.1%	23.7 7.9%	22.0 7.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Maternal Chloroquine Prophylaxis, Maternal SP IPT
	Comments	The null hypothesis is the incidence of maternal anemia is identical between subjects receiving maternal chloroquine prophylaxis vs. maternal SP IPT.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3089
	Comments	A Bonferroni correction was used due to multiple comparisons. Comparisons are statistically significant if the two-sided p-value is ≤ 0.05/2=0.025.
	Method	Fisher Exact
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Maternal Chloroquine IPT, Maternal SP IPT
	Comments	The null hypothesis is the incidence of maternal anemia is identical between subjects receiving maternal chloroquine IPT vs. maternal SP IPT.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6973
	Comments	A Bonferroni correction was used due to multiple comparisons. Comparisons are statistically significant if the two-sided p-value is ≤ 0.05/2=0.025.
	Method	Fisher Exact
	Comments

4. Secondary Outcome

Title	Incidence of Maternal Severe Anemia (Hemoglobin < 7gm/dl)
Description	Maternal participants were followed to outcome of the pregnancy. The outcome measure provides the incidence of severe anemia among maternal participants during pregnancy. Severe anemia is defined as having a hemoglobin value less than 7 gm/dl.
Time Frame	From enrollment until delivery, approximately 12-36 weeks

Outcome Measure Data

Analysis Population Description

The analysis population includes all maternal participants.

Arm/Group Title	Maternal Chloroquine Prophylaxis	Maternal Chloroquine IPT	Maternal SP IPT
Arm/Group Description	Maternal participants receive a loading dose of chloroquine (base) 600 mg (2 tablets) at first administration followed by 300 mg of chloroquine base (1 tablet) every week until delivery.	Maternal participants receive a therapeutic dose of chloroquine (1,500 mg given over 3 days, 2 tablets on Day 0, 2 tablets on Day 1, 1 tablet on Day 2) administered twice during pregnancy at 20-28 weeks and at 28-34 weeks.	Maternal participants receive a therapeutic dose of sulfadoxine-pyrimethamine (SP), (1500 mg sulfadoxine and 75 mg pyrimethamine (3 tablets)) administered twice during pregnancy at 20-28 weeks and at 28-34 weeks.
Measure Participants	300	300	300
Number (97.5% Confidence Interval) [percentage of maternal participants]	0.0 0%	0.3 0.1%	0.3 0.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Maternal Chloroquine Prophylaxis, Maternal SP IPT
	Comments	The null hypothesis is the incidence of maternal severe anemia is identical between subjects receiving maternal chloroquine prophylaxis vs. maternal SP IPT.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	1.00
	Comments	A Bonferroni correction was used due to multiple comparisons. Comparisons are statistically significant if the two-sided p-value is ≤ 0.05/2=0.025.
	Method	Fisher Exact
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Maternal Chloroquine IPT, Maternal SP IPT
	Comments	The null hypothesis is the incidence of maternal severe anemia is identical between subjects receiving maternal chloroquine IPT vs. maternal SP IPT.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	1.00
	Comments	A Bonferroni correction was used due to multiple comparisons. Comparisons are statistically significant if the two-sided p-value is ≤ 0.05/2=0.025.
	Method	Fisher Exact
	Comments

5. Secondary Outcome

Title	Incidence of Stillbirth
Description	Maternal participants were followed to outcome of the pregnancy. The outcome measure provides the incidence of participants' deliveries whose outcome was stillbirth, defined as an infant born without any signs of life at 28 weeks or greater of gestation.
Time Frame	At delivery: Approximately 12-36 weeks after enrollment

Outcome Measure Data

Analysis Population Description

The analysis population includes all participants whose pregnancies were followed to delivery.

Arm/Group Title	Maternal Chloroquine Prophylaxis	Maternal Chloroquine IPT	Maternal SP IPT
Arm/Group Description	Maternal participants receive a loading dose of chloroquine (base) 600 mg (2 tablets) at first administration followed by 300 mg of chloroquine base (1 tablet) every week until delivery.	Maternal participants receive a therapeutic dose of chloroquine (1,500 mg given over 3 days, 2 tablets on Day 0, 2 tablets on Day 1, 1 tablet on Day 2) administered twice during pregnancy at 20-28 weeks and at 28-34 weeks.	Maternal participants receive a therapeutic dose of sulfadoxine-pyrimethamine (SP), (1500 mg sulfadoxine and 75 mg pyrimethamine (3 tablets)) administered twice during pregnancy at 20-28 weeks and at 28-34 weeks.
Measure Participants	272	273	263
Number (97.5% Confidence Interval) [percentage of deliveries]	1.10	0.37	1.90

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Maternal Chloroquine Prophylaxis, Maternal SP IPT
	Comments	The null hypothesis is the incidence of stillbirth is identical between subjects receiving maternal chloroquine prophylaxis vs. maternal SP IPT.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4979
	Comments	A Bonferroni correction was used due to multiple comparisons. Comparisons are statistically significant if the two-sided p-value is ≤ 0.05/2=0.025.
	Method	Fisher Exact
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Maternal Chloroquine IPT, Maternal SP IPT
	Comments	The null hypothesis is the incidence of stillbirth is identical between subjects receiving maternal chloroquine IPT vs. maternal SP IPT.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1166
	Comments	A Bonferroni correction was used due to multiple comparisons. Comparisons are statistically significant if the two-sided p-value is ≤ 0.05/2=0.025.
	Method	Fisher Exact
	Comments

6. Secondary Outcome

Title	Incidence of Miscarriage
Description	Maternal participants were followed to outcome of the pregnancy. The outcome measure provides the incidence of participants' deliveries whose outcome was miscarriage, defined as an infant delivered without any signs of life at less than 28 weeks of gestation.
Time Frame	At delivery: Approximately 12-36 weeks after enrollment

Outcome Measure Data

Analysis Population Description

The analysis population includes all maternal participants.

Arm/Group Title	Maternal Chloroquine Prophylaxis	Maternal Chloroquine IPT	Maternal SP IPT
Arm/Group Description	Maternal participants receive a loading dose of chloroquine (base) 600 mg (2 tablets) at first administration followed by 300 mg of chloroquine base (1 tablet) every week until delivery.	Maternal participants receive a therapeutic dose of chloroquine (1,500 mg given over 3 days, 2 tablets on Day 0, 2 tablets on Day 1, 1 tablet on Day 2) administered twice during pregnancy at 20-28 weeks and at 28-34 weeks.	Maternal participants receive a therapeutic dose of sulfadoxine-pyrimethamine (SP), (1500 mg sulfadoxine and 75 mg pyrimethamine (3 tablets)) administered twice during pregnancy at 20-28 weeks and at 28-34 weeks.
Measure Participants	300	300	300
Number (97.5% Confidence Interval) [percentage of pregnancies]	0.33	0.67	1.00

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Maternal Chloroquine Prophylaxis, Maternal SP IPT
	Comments	The null hypothesis is the incidence of miscarriage is identical between subjects receiving maternal chloroquine prophylaxis vs. maternal SP IPT.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6237
	Comments	A Bonferroni correction was used due to multiple comparisons. Comparisons are statistically significant if the two-sided p-value is ≤ 0.05/2=0.025.
	Method	Fisher Exact
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Maternal Chloroquine IPT, Maternal SP IPT
	Comments	The null hypothesis is the incidence of miscarriage is identical between subjects receiving maternal chloroquine IPT vs. maternal SP IPT.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	1.000
	Comments	A Bonferroni correction was used due to multiple comparisons. Comparisons are statistically significant if the two-sided p-value is ≤ 0.05/2=0.025.
	Method	Fisher Exact
	Comments

7. Secondary Outcome

Title	Incidence of Preterm Delivery
Description	Maternal participants were followed to outcome of the pregnancy. The outcome measure provides the incidence of participants' deliveries whose outcome was preterm delivery, defined as delivery less than 37 weeks of gestation. The outcome of the delivery was not considered, and could have been live birth, stillbirth, or miscarriage.
Time Frame	At delivery: Approximately 12-36 weeks after enrollment

Outcome Measure Data

Analysis Population Description

The analysis population includes all participants whose pregnancies were followed to delivery.

Arm/Group Title	Maternal Chloroquine Prophylaxis	Maternal Chloroquine IPT	Maternal SP IPT
Arm/Group Description	Maternal participants receive a loading dose of chloroquine (base) 600 mg (2 tablets) at first administration followed by 300 mg of chloroquine base (1 tablet) every week until delivery.	Maternal participants receive a therapeutic dose of chloroquine (1,500 mg given over 3 days, 2 tablets on Day 0, 2 tablets on Day 1, 1 tablet on Day 2) administered twice during pregnancy at 20-28 weeks and at 28-34 weeks.	Maternal participants receive a therapeutic dose of sulfadoxine-pyrimethamine (SP), (1500 mg sulfadoxine and 75 mg pyrimethamine (3 tablets)) administered twice during pregnancy at 20-28 weeks and at 28-34 weeks.
Measure Participants	272	273	263
Number (97.5% Confidence Interval) [percentage of deliveries]	8.46	9.89	6.84

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Maternal Chloroquine Prophylaxis, Maternal SP IPT
	Comments	The null hypothesis is the incidence of preterm delivery is identical between subjects receiving maternal chloroquine prophylaxis vs. maternal SP IPT.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5187
	Comments	A Bonferroni correction was used due to multiple comparisons. Comparisons are statistically significant if the two-sided p-value is ≤ 0.05/2=0.025.
	Method	Fisher Exact
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Maternal Chloroquine IPT, Maternal SP IPT
	Comments	The null hypothesis is the incidence of preterm delivery is identical between subjects receiving maternal chloroquine IPT vs. maternal SP IPT.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2163
	Comments	A Bonferroni correction was used due to multiple comparisons. Comparisons are statistically significant if the two-sided p-value is ≤ 0.05/2=0.025.
	Method	Fisher Exact
	Comments

8. Secondary Outcome

Title	Infant Mortality Rate to 14 Weeks of Age
Description	Infants were followed from the time of delivery until 14 weeks of age. This outcome measure provides the incidence of infants who died within 14 weeks of delivery.
Time Frame	For 14 weeks after delivery.

Outcome Measure Data

Analysis Population Description

The analysis population includes all enrolled infants.

Arm/Group Title	Infant Chloroquine Prophylaxis	Infant Chloroquine IPT	Infant SP IPT
Arm/Group Description	Infants born to maternal participants who received chloroquine prophylaxis.	Infants born to maternal participants who received chloroquine IPT.	Infants born to maternal participants who received SP IPT.
Measure Participants	270	274	259
Number (97.5% Confidence Interval) [percentage of infants]	2.22	3.65	3.09

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Maternal Chloroquine Prophylaxis, Maternal SP IPT
	Comments	The null hypothesis is the incidence of infant mortality within 14 weeks of delivery is identical between subjects receiving maternal chloroquine prophylaxis vs. maternal SP IPT.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5959
	Comments	A Bonferroni correction was used due to multiple comparisons. Comparisons are statistically significant if the two-sided p-value is ≤ 0.05/2=0.025.
	Method	Fisher Exact
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Maternal Chloroquine IPT, Maternal SP IPT
	Comments	The null hypothesis is the incidence of infant mortality within 14 weeks of delivery is identical between subjects receiving maternal chloroquine IPT vs. maternal SP IPT.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8127
	Comments	A Bonferroni correction was used due to multiple comparisons. Comparisons are statistically significant if the two-sided p-value is ≤ 0.05/2=0.025.
	Method	Fisher Exact
	Comments

9. Secondary Outcome

Title	Incidence of Low Birth Weight (LBW) (Birthweight < 2500 Grams)
Description	Maternal participants were followed to outcome of the pregnancy. The outcome measure provides the incidence of infants whose birthweight was less than 2500 grams.
Time Frame	At delivery: Approximately 12-36 weeks after enrollment

Outcome Measure Data

Analysis Population Description

The analysis population includes all infants born alive with weight data collected at birth.

Arm/Group Title	Infant Chloroquine Prophylaxis	Infant Chloroquine IPT	Infant SP IPT
Arm/Group Description	Infants born to maternal participants who received chloroquine prophylaxis.	Infants born to maternal participants who received chloroquine IPT.	Infants born to maternal participants who received SP IPT.
Measure Participants	263	264	256
Number (97.5% Confidence Interval) [percentage of infants]	15.59	10.98	12.11

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Maternal Chloroquine Prophylaxis, Maternal SP IPT
	Comments	The null hypothesis is the incidence of low birth weight is identical between subjects receiving maternal chloroquine prophylaxis vs. maternal SP IPT.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2566
	Comments	A Bonferroni correction was used due to multiple comparisons. Comparisons are statistically significant if the two-sided p-value is ≤ 0.05/2=0.025.
	Method	Fisher Exact
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Maternal Chloroquine IPT, Maternal SP IPT
	Comments	The null hypothesis is the incidence of low birth weight is identical between subjects receiving maternal chloroquine IPT vs. maternal SP IPT.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7839
	Comments	A Bonferroni correction was used due to multiple comparisons. Comparisons are statistically significant if the two-sided p-value is ≤ 0.05/2=0.025.
	Method	Fisher Exact
	Comments

10. Secondary Outcome

Title	Incidence of Intrauterine Growth Restriction (IUGR)
Description	Infants were followed from the time of delivery until 14 weeks of age. This outcome measure provides the incidence of infants with IUGR at delivery. IUGR is defined as weight below the 10th percentile for gestational age based on the World Health Organization (WHO) fetal growth curve. This classification is supported by literature resulting from the INTERGROWTH-21st Project; José Villar.
Time Frame	At delivery: Approximately 12-36 weeks after enrollment

Outcome Measure Data

Analysis Population Description

This analysis population includes all infants with weight captured at delivery and with mothers having reported gestational age at delivery.

Arm/Group Title	Infant Chloroquine Prophylaxis	Infant Chloroquine IPT	Infant SP IPT
Arm/Group Description	Infants born to maternal participants who received chloroquine prophylaxis.	Infants born to maternal participants who received chloroquine IPT.	Infants born to maternal participants who received SP IPT.
Measure Participants	260	261	250
Number (97.5% Confidence Interval) [percentage of participants]	16.54 5.5%	18.01 6%	20.80 6.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Maternal Chloroquine Prophylaxis, Maternal SP IPT
	Comments	The null hypothesis is the incidence of intrauterine growth restriction is identical between subjects receiving maternal chloroquine prophylaxis vs. maternal SP IPT.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2553
	Comments	A Bonferroni correction was used due to multiple comparisons. Comparisons are statistically significant if the two-sided p-value is ≤ 0.05/2=0.025.
	Method	Fisher Exact
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Maternal Chloroquine IPT, Maternal SP IPT
	Comments	The null hypothesis is the incidence of intrauterine growth restriction is identical between subjects receiving maternal chloroquine IPT vs. maternal SP IPT.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4354
	Comments	A Bonferroni correction was used due to multiple comparisons. Comparisons are statistically significant if the two-sided p-value is ≤ 0.05/2=0.025.
	Method	Fisher Exact
	Comments

11. Secondary Outcome

Title	Incidence of Active Placental Malaria Infection
Description	Maternal participants were followed to outcome of the pregnancy. This outcome measure provides the number of placental malaria infections in maternal subjects diagnosed by the presence of parasites and/or pigment on histological section or molecular evidence of infection (PCR).
Time Frame	At delivery: Approximately 12-36 weeks after enrollment

Outcome Measure Data

Analysis Population Description

This analysis population includes all maternal subjects with placental slides reviewed and PCR results obtained.

Arm/Group Title	Maternal Chloroquine Prophylaxis	Maternal Chloroquine IPT	Maternal SP IPT
Arm/Group Description	Maternal participants receive a loading dose of chloroquine (base) 600 mg (2 tablets) at first administration followed by 300 mg of chloroquine base (1 tablet) every week until delivery.	Maternal participants receive a therapeutic dose of chloroquine (1,500 mg given over 3 days, 2 tablets on Day 0, 2 tablets on Day 1, 1 tablet on Day 2) administered twice during pregnancy at 20-28 weeks and at 28-34 weeks.	Maternal participants receive a therapeutic dose of sulfadoxine-pyrimethamine (SP), (1500 mg sulfadoxine and 75 mg pyrimethamine (3 tablets)) administered twice during pregnancy at 20-28 weeks and at 28-34 weeks.
Measure Participants	259	253	253
Number (97.5% Confidence Interval) [percentage of participants]	3.09 1%	3.16 1.1%	4.74 1.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Maternal Chloroquine Prophylaxis, Maternal SP IPT
	Comments	The null hypothesis is the incidence of active placental malaria infection is identical between subjects receiving maternal chloroquine prophylaxis vs. maternal SP IPT.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3690
	Comments	A Bonferroni correction was used due to multiple comparisons. Comparisons are statistically significant if the two-sided p-value is ≤ 0.05/2=0.025.
	Method	Fisher Exact
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Maternal Chloroquine IPT, Maternal SP IPT
	Comments	The null hypothesis is the incidence of active placental malaria infection is identical between subjects receiving maternal chloroquine IPT vs. maternal SP IPT.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4947
	Comments	A Bonferroni correction was used due to multiple comparisons. Comparisons are statistically significant if the two-sided p-value is ≤ 0.05/2=0.025.
	Method	Fisher Exact
	Comments

12. Secondary Outcome

Title	Incidence of Malaria Infection, All Species.
Description	Maternal participants were followed to outcome of the pregnancy. This outcome measure provides the number of malaria infection episodes measured by positive parasitemia in maternal subjects.
Time Frame	Enrollment to delivery (approximately 12-36 weeks)

Outcome Measure Data

Analysis Population Description

The analysis population includes all maternal participants.

Arm/Group Title	Maternal Chloroquine Prophylaxis	Maternal Chloroquine IPT	Maternal SP IPT
Arm/Group Description	Maternal participants receive a loading dose of chloroquine (base) 600 mg (2 tablets) at first administration followed by 300 mg of chloroquine base (1 tablet) every week until delivery.	Maternal participants receive a therapeutic dose of chloroquine (1,500 mg given over 3 days, 2 tablets on Day 0, 2 tablets on Day 1, 1 tablet on Day 2) administered twice during pregnancy at 20-28 weeks and at 28-34 weeks.	Maternal participants receive a therapeutic dose of sulfadoxine-pyrimethamine (SP), (1500 mg sulfadoxine and 75 mg pyrimethamine (3 tablets)) administered twice during pregnancy at 20-28 weeks and at 28-34 weeks.
Measure Participants	300	300	300
Number (97.5% Confidence Interval) [percentage of participants]	0.67 0.2%	1.67 0.6%	3.00 1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Maternal Chloroquine Prophylaxis, Maternal SP IPT
	Comments	The null hypothesis is the incidence of malaria infection (all species) measured by positive parasitemia is identical between subjects receiving maternal chloroquine prophylaxis vs. maternal SP IPT.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0630
	Comments	A Bonferroni correction was used due to multiple comparisons. Comparisons are statistically significant if the two-sided p-value is ≤ 0.05/2=0.025.
	Method	Fisher Exact
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Maternal Chloroquine IPT, Maternal SP IPT
	Comments	The null hypothesis is the incidence of malaria infection (all species) measured by positive parasitemia is identical between subjects receiving maternal chloroquine IPT vs. maternal SP IPT.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4184
	Comments	A Bonferroni correction was used due to multiple comparisons. Comparisons are statistically significant if the two-sided p-value is ≤ 0.05/2=0.025.
	Method	Fisher Exact
	Comments

13. Secondary Outcome

Title	Incidence of Clinical Malaria, All Species
Description	Maternal participants were followed to outcome of the pregnancy. Clinical malaria is defined as malaria infection at any parasite density with associated symptoms including at least one of the following: objective fever measured at the clinic, history of fever in the past 48 hours or other symptoms in the last 48 hours including: headache, myalgia, vomiting, or weakness.
Time Frame	Enrollment to delivery (approximately 12-36 weeks)

Outcome Measure Data

Analysis Population Description

The analysis population includes all maternal participants.

Arm/Group Title	Maternal Chloroquine Prophylaxis	Maternal Chloroquine IPT	Maternal SP IPT
Arm/Group Description	Maternal participants receive a loading dose of chloroquine (base) 600 mg (2 tablets) at first administration followed by 300 mg of chloroquine base (1 tablet) every week until delivery.	Maternal participants receive a therapeutic dose of chloroquine (1,500 mg given over 3 days, 2 tablets on Day 0, 2 tablets on Day 1, 1 tablet on Day 2) administered twice during pregnancy at 20-28 weeks and at 28-34 weeks.	Maternal participants receive a therapeutic dose of sulfadoxine-pyrimethamine (SP), (1500 mg sulfadoxine and 75 mg pyrimethamine (3 tablets)) administered twice during pregnancy at 20-28 weeks and at 28-34 weeks.
Measure Participants	300	300	300
Number (97.5% Confidence Interval) [percentage of participants]	0.67 0.2%	1.33 0.4%	3.00 1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Maternal Chloroquine Prophylaxis, Maternal SP IPT
	Comments	The null hypothesis is the incidence of clinical malaria (all species) is identical between subjects receiving maternal chloroquine prophylaxis vs. maternal SP IPT.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0268
	Comments	A Bonferroni correction was used due to multiple comparisons. Comparisons are statistically significant if the two-sided p-value is ≤ 0.05/2=0.025.
	Method	Cox proportional hazards
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Maternal Chloroquine IPT, Maternal SP IPT
	Comments	The null hypothesis is the incidence of clinical malaria (all species) is identical between subjects receiving maternal chloroquine IPT vs. maternal SP IPT.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1646
	Comments	A Bonferroni correction was used due to multiple comparisons. Comparisons are statistically significant if the two-sided p-value is ≤ 0.05/2=0.025.
	Method	Cox proportional hazards
	Comments

14. Secondary Outcome

Title	Incidence of Infection in the Fetal Circulation
Description	Maternal participants were followed to outcome of the pregnancy. This outcome measure provides the number of positive for malaria cord blood smear and cord PCR results in maternal subjects based on the results of the thick smear and PCR from the cord blood sample.
Time Frame	At delivery: Approximately 12-36 weeks after enrollment

Outcome Measure Data

Analysis Population Description

The analysis population includes all maternal participants with cord blood smears and cord PCR results obtained.

Arm/Group Title	Maternal Chloroquine Prophylaxis	Maternal Chloroquine IPT	Maternal SP IPT
Arm/Group Description	Maternal participants receive a loading dose of chloroquine (base) 600 mg (2 tablets) at first administration followed by 300 mg of chloroquine base (1 tablet) every week until delivery.	Maternal participants receive a therapeutic dose of chloroquine (1,500 mg given over 3 days, 2 tablets on Day 0, 2 tablets on Day 1, 1 tablet on Day 2) administered twice during pregnancy at 20-28 weeks and at 28-34 weeks.	Maternal participants receive a therapeutic dose of sulfadoxine-pyrimethamine (SP), (1500 mg sulfadoxine and 75 mg pyrimethamine (3 tablets)) administered twice during pregnancy at 20-28 weeks and at 28-34 weeks.
Measure Participants	257	252	251
Number (97.5% Confidence Interval) [percentage of participants]	1.95 0.7%	2.78 0.9%	0.80 0.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Maternal Chloroquine Prophylaxis, Maternal SP IPT
	Comments	The null hypothesis is the incidence of infection in the fetal circulation is identical between subjects receiving maternal chloroquine prophylaxis vs. maternal SP IPT.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4501
	Comments	A Bonferroni correction was used due to multiple comparisons. Comparisons are statistically significant if the two-sided p-value is ≤ 0.05/2=0.025.
	Method	Fisher Exact
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Maternal Chloroquine IPT, Maternal SP IPT
	Comments	The null hypothesis is the incidence of infection in the fetal circulation is identical between subjects receiving maternal chloroquine IPT vs. maternal SP IPT.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1758
	Comments	A Bonferroni correction was used due to multiple comparisons. Comparisons are statistically significant if the two-sided p-value is ≤ 0.05/2=0.025.
	Method	Fisher Exact
	Comments

Adverse Events

Time Frame	Adverse events and serious adverse events were collected after the administration of the first dose of study drug throughout the duration of the follow-up period (approximately 14 weeks following delivery).
Arm/Group Title	Maternal Chloroquine Prophylaxis		Maternal Chloroquine IPT		Maternal SP IPT		Infant Chloroquine Prophylaxis		Infant Chloroquine IPT		Infant SP IPT
Arm/Group Description	Maternal participants receive a loading dose of chloroquine (base) 600 mg (2 tablets) at first administration followed by 300 mg of chloroquine base (1 tablet) every week until delivery.		Maternal participants receive a therapeutic dose of chloroquine (1,500 mg given over 3 days, 2 tablets on Day 0, 2 tablets on Day 1, 1 tablet on Day 2) administered twice during pregnancy at 20-28 weeks and at 28-34 weeks.		Maternal participants receive a therapeutic dose of sulfadoxine-pyrimethamine (SP), (1500 mg sulfadoxine and 75 mg pyrimethamine (3 tablets)) administered twice during pregnancy at 20-28 weeks and at 28-34 weeks.		Infants born to maternal participants who received chloroquine prophylaxis.		Infants born to maternal participants who received chloroquine IPT.		Infants born to maternal participants who received SP IPT.
All Cause Mortality
	Maternal Chloroquine Prophylaxis		Maternal Chloroquine IPT		Maternal SP IPT		Infant Chloroquine Prophylaxis		Infant Chloroquine IPT		Infant SP IPT
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Maternal Chloroquine Prophylaxis		Maternal Chloroquine IPT		Maternal SP IPT		Infant Chloroquine Prophylaxis		Infant Chloroquine IPT		Infant SP IPT
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	23/300 (7.7%)		29/300 (9.7%)		26/300 (8.7%)		46/270 (17%)		65/274 (23.7%)		43/259 (16.6%)
Blood and lymphatic system disorders
Anaemia	1/300 (0.3%)	1	0/300 (0%)	0	0/300 (0%)	0	0/270 (0%)	0	0/274 (0%)	0	0/259 (0%)	0
Anaemia of pregnancy	0/300 (0%)	0	0/300 (0%)	0	1/300 (0.3%)	1	0/270 (0%)	0	0/274 (0%)	0	0/259 (0%)	0
Cardiac disorders
Cardio-respiratory arrest	0/300 (0%)	0	0/300 (0%)	0	0/300 (0%)	0	1/270 (0.4%)	1	0/274 (0%)	0	0/259 (0%)	0
Congenital, familial and genetic disorders
Accessory auricle	0/300 (0%)	0	0/300 (0%)	0	0/300 (0%)	0	1/270 (0.4%)	1	0/274 (0%)	0	0/259 (0%)	0
Dermoid cyst	0/300 (0%)	0	0/300 (0%)	0	0/300 (0%)	0	1/270 (0.4%)	1	0/274 (0%)	0	0/259 (0%)	0
Heart disease congenital	0/300 (0%)	0	0/300 (0%)	0	0/300 (0%)	0	0/270 (0%)	0	1/274 (0.4%)	1	0/259 (0%)	0
Laryngomalacia	0/300 (0%)	0	0/300 (0%)	0	0/300 (0%)	0	1/270 (0.4%)	1	1/274 (0.4%)	2	1/259 (0.4%)	1
Polydactyly	0/300 (0%)	0	0/300 (0%)	0	0/300 (0%)	0	6/270 (2.2%)	6	9/274 (3.3%)	9	6/259 (2.3%)	6
Talipes	0/300 (0%)	0	0/300 (0%)	0	0/300 (0%)	0	0/270 (0%)	0	2/274 (0.7%)	2	0/259 (0%)	0
Umbilical cord haemorrhage	0/300 (0%)	0	0/300 (0%)	0	0/300 (0%)	0	1/270 (0.4%)	1	0/274 (0%)	0	0/259 (0%)	0
Gastrointestinal disorders
Constipation	0/300 (0%)	0	1/300 (0.3%)	1	0/300 (0%)	0	0/270 (0%)	0	1/274 (0.4%)	1	0/259 (0%)	0
General disorders
Death neonatal	0/300 (0%)	0	0/300 (0%)	0	0/300 (0%)	0	1/270 (0.4%)	1	0/274 (0%)	0	0/259 (0%)	0
Pyrexia	0/300 (0%)	0	0/300 (0%)	0	0/300 (0%)	0	0/270 (0%)	0	2/274 (0.7%)	2	2/259 (0.8%)	2
Sudden infant death syndrome	0/300 (0%)	0	0/300 (0%)	0	0/300 (0%)	0	1/270 (0.4%)	1	2/274 (0.7%)	2	0/259 (0%)	0
Hepatobiliary disorders
Hyperbilirubinaemia	0/300 (0%)	0	0/300 (0%)	0	0/300 (0%)	0	1/270 (0.4%)	1	1/274 (0.4%)	1	1/259 (0.4%)	1
Infections and infestations
Bartholin's abscess	0/300 (0%)	0	0/300 (0%)	0	1/300 (0.3%)	1	0/270 (0%)	0	0/274 (0%)	0	0/259 (0%)	0
Dysentery	0/300 (0%)	0	0/300 (0%)	0	1/300 (0.3%)	1	0/270 (0%)	0	0/274 (0%)	0	0/259 (0%)	0
Gastroenteritis	1/300 (0.3%)	1	0/300 (0%)	0	0/300 (0%)	0	0/270 (0%)	0	1/274 (0.4%)	1	0/259 (0%)	0
Incision site infection	1/300 (0.3%)	1	0/300 (0%)	0	0/300 (0%)	0	0/270 (0%)	0	0/274 (0%)	0	0/259 (0%)	0
Malaria	0/300 (0%)	0	1/300 (0.3%)	1	1/300 (0.3%)	1	0/270 (0%)	0	0/274 (0%)	0	0/259 (0%)	0
Peritonitis	1/300 (0.3%)	1	0/300 (0%)	0	0/300 (0%)	0	0/270 (0%)	0	0/274 (0%)	0	0/259 (0%)	0
Pneumonia	1/300 (0.3%)	1	0/300 (0%)	0	0/300 (0%)	0	2/270 (0.7%)	2	3/274 (1.1%)	3	0/259 (0%)	0
Postoperative wound infection	0/300 (0%)	0	2/300 (0.7%)	2	0/300 (0%)	0	0/270 (0%)	0	0/274 (0%)	0	0/259 (0%)	0
Postpartum sepsis	2/300 (0.7%)	2	0/300 (0%)	0	1/300 (0.3%)	1	0/270 (0%)	0	0/274 (0%)	0	0/259 (0%)	0
Urinary tract infection	3/300 (1%)	3	1/300 (0.3%)	1	4/300 (1.3%)	4	0/270 (0%)	0	0/274 (0%)	0	0/259 (0%)	0
Wound infection	0/300 (0%)	0	1/300 (0.3%)	1	1/300 (0.3%)	1	0/270 (0%)	0	0/274 (0%)	0	0/259 (0%)	0
Abscess	0/300 (0%)	0	0/300 (0%)	0	0/300 (0%)	0	1/270 (0.4%)	1	0/274 (0%)	0	0/259 (0%)	0
Bronchiolitis	0/300 (0%)	0	0/300 (0%)	0	0/300 (0%)	0	5/270 (1.9%)	5	4/274 (1.5%)	4	1/259 (0.4%)	1
Group B streptococcus neonatal sepsis	0/300 (0%)	0	0/300 (0%)	0	0/300 (0%)	0	1/270 (0.4%)	1	0/274 (0%)	0	0/259 (0%)	0
Pneumocystis jirovecii pneumonia	0/300 (0%)	0	0/300 (0%)	0	0/300 (0%)	0	2/270 (0.7%)	2	0/274 (0%)	0	0/259 (0%)	0
Sepsis	0/300 (0%)	0	0/300 (0%)	0	0/300 (0%)	0	1/270 (0.4%)	1	2/274 (0.7%)	2	0/259 (0%)	0
Sepsis neonatal	0/300 (0%)	0	0/300 (0%)	0	0/300 (0%)	0	6/270 (2.2%)	6	10/274 (3.6%)	10	12/259 (4.6%)	12
Staphylococcal sepsis	0/300 (0%)	0	0/300 (0%)	0	0/300 (0%)	0	0/270 (0%)	0	1/274 (0.4%)	1	0/259 (0%)	0
Upper respiratory tract infection	0/300 (0%)	0	0/300 (0%)	0	0/300 (0%)	0	2/270 (0.7%)	2	0/274 (0%)	0	0/259 (0%)	0
Metabolism and nutrition disorders
Failure to thrive	0/300 (0%)	0	0/300 (0%)	0	0/300 (0%)	0	2/270 (0.7%)	2	0/274 (0%)	0	0/259 (0%)	0
Feeding disorder neonatal	0/300 (0%)	0	0/300 (0%)	0	0/300 (0%)	0	1/270 (0.4%)	1	0/274 (0%)	0	1/259 (0.4%)	1
Marasmus	0/300 (0%)	0	0/300 (0%)	0	0/300 (0%)	0	1/270 (0.4%)	1	0/274 (0%)	0	0/259 (0%)	0
Musculoskeletal and connective tissue disorders
Muscular weakness	0/300 (0%)	0	1/300 (0.3%)	1	0/300 (0%)	0	0/270 (0%)	0	0/274 (0%)	0	0/259 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Haemangioma	0/300 (0%)	0	0/300 (0%)	0	0/300 (0%)	0	0/270 (0%)	0	1/274 (0.4%)	1	0/259 (0%)	0
Nervous system disorders
Hypoxic-ischaemic encephalopathy	0/300 (0%)	0	0/300 (0%)	0	0/300 (0%)	0	0/270 (0%)	0	1/274 (0.4%)	1	2/259 (0.8%)	2
Myoclonus	0/300 (0%)	0	0/300 (0%)	0	0/300 (0%)	0	1/270 (0.4%)	1	0/274 (0%)	0	0/259 (0%)	0
Pregnancy, puerperium and perinatal conditions
Abortion incomplete	0/300 (0%)	0	1/300 (0.3%)	1	1/300 (0.3%)	1	0/270 (0%)	0	0/274 (0%)	0	0/259 (0%)	0
Abortion spontaneous	1/300 (0.3%)	1	1/300 (0.3%)	1	2/300 (0.7%)	2	0/270 (0%)	0	0/274 (0%)	0	0/259 (0%)	0
Abortion threatened	1/300 (0.3%)	1	2/300 (0.7%)	2	0/300 (0%)	0	0/270 (0%)	0	0/274 (0%)	0	0/259 (0%)	0
Eclampsia	3/300 (1%)	3	3/300 (1%)	3	0/300 (0%)	0	0/270 (0%)	0	0/274 (0%)	0	0/259 (0%)	0
Foetal death	3/300 (1%)	3	1/300 (0.3%)	1	4/300 (1.3%)	4	0/270 (0%)	0	0/274 (0%)	0	0/259 (0%)	0
Gestational hypertension	0/300 (0%)	0	1/300 (0.3%)	1	0/300 (0%)	0	0/270 (0%)	0	0/274 (0%)	0	0/259 (0%)	0
Haemorrhage in pregnancy	1/300 (0.3%)	2	0/300 (0%)	0	0/300 (0%)	0	0/270 (0%)	0	0/274 (0%)	0	0/259 (0%)	0
Postpartum haemorrhage	1/300 (0.3%)	1	1/300 (0.3%)	1	1/300 (0.3%)	1	0/270 (0%)	0	0/274 (0%)	0	0/259 (0%)	0
Pre-eclampsia	1/300 (0.3%)	1	2/300 (0.7%)	2	0/300 (0%)	0	0/270 (0%)	0	0/274 (0%)	0	0/259 (0%)	0
Premature delivery	2/300 (0.7%)	2	0/300 (0%)	0	1/300 (0.3%)	1	1/270 (0.4%)	1	0/274 (0%)	0	0/259 (0%)	0
Premature labour	2/300 (0.7%)	2	6/300 (2%)	6	5/300 (1.7%)	5	0/270 (0%)	0	0/274 (0%)	0	0/259 (0%)	0
Premature rupture of membranes	1/300 (0.3%)	1	1/300 (0.3%)	1	0/300 (0%)	0	0/270 (0%)	0	0/274 (0%)	0	0/259 (0%)	0
Preterm premature rupture of membranes	0/300 (0%)	0	1/300 (0.3%)	1	0/300 (0%)	0	0/270 (0%)	0	0/274 (0%)	0	0/259 (0%)	0
Prolonged rupture of membranes	0/300 (0%)	0	1/300 (0.3%)	1	0/300 (0%)	0	0/270 (0%)	0	0/274 (0%)	0	0/259 (0%)	0
Stillbirth	0/300 (0%)	0	0/300 (0%)	0	1/300 (0.3%)	1	0/270 (0%)	0	0/274 (0%)	0	0/259 (0%)	0
Uterine contractions during pregnancy	0/300 (0%)	0	1/300 (0.3%)	1	1/300 (0.3%)	1	0/270 (0%)	0	0/274 (0%)	0	0/259 (0%)	0
Jaundice neonatal	0/300 (0%)	0	0/300 (0%)	0	0/300 (0%)	0	0/270 (0%)	0	1/274 (0.4%)	1	0/259 (0%)	0
Low birth weight baby	0/300 (0%)	0	0/300 (0%)	0	0/300 (0%)	0	0/270 (0%)	0	2/274 (0.7%)	2	1/259 (0.4%)	1
Premature baby	0/300 (0%)	0	0/300 (0%)	0	0/300 (0%)	0	5/270 (1.9%)	5	9/274 (3.3%)	9	2/259 (0.8%)	2
Psychiatric disorders
Brief psychotic disorder, with postpartum onset	0/300 (0%)	0	1/300 (0.3%)	1	0/300 (0%)	0	0/270 (0%)	0	0/274 (0%)	0	0/259 (0%)	0
Psychotic disorder	0/300 (0%)	0	1/300 (0.3%)	1	0/300 (0%)	0	0/270 (0%)	0	0/274 (0%)	0	0/259 (0%)	0
Reproductive system and breast disorders
Vaginal haemorrhage	0/300 (0%)	0	1/300 (0.3%)	1	0/300 (0%)	0	0/270 (0%)	0	0/274 (0%)	0	0/259 (0%)	0
Respiratory, thoracic and mediastinal disorders
Aspiration	0/300 (0%)	0	0/300 (0%)	0	0/300 (0%)	0	0/270 (0%)	0	1/274 (0.4%)	1	0/259 (0%)	0
Neonatal asphyxia	0/300 (0%)	0	0/300 (0%)	0	0/300 (0%)	0	6/270 (2.2%)	6	2/274 (0.7%)	2	8/259 (3.1%)	8
Neonatal aspiration	0/300 (0%)	0	0/300 (0%)	0	0/300 (0%)	0	1/270 (0.4%)	1	2/274 (0.7%)	2	1/259 (0.4%)	1
Neonatal respiratory distress syndrome	0/300 (0%)	0	0/300 (0%)	0	0/300 (0%)	0	0/270 (0%)	0	3/274 (1.1%)	3	3/259 (1.2%)	3
Respiratory arrest	0/300 (0%)	0	0/300 (0%)	0	0/300 (0%)	0	0/270 (0%)	0	0/274 (0%)	0	1/259 (0.4%)	1
Respiratory distress	0/300 (0%)	0	0/300 (0%)	0	0/300 (0%)	0	1/270 (0.4%)	1	2/274 (0.7%)	2	3/259 (1.2%)	3
Transient tachypnoea of the newborn	0/300 (0%)	0	0/300 (0%)	0	0/300 (0%)	0	1/270 (0.4%)	1	6/274 (2.2%)	6	3/259 (1.2%)	3
Skin and subcutaneous tissue disorders
Melanosis	0/300 (0%)	0	0/300 (0%)	0	0/300 (0%)	0	0/270 (0%)	0	1/274 (0.4%)	1	0/259 (0%)	0
Surgical and medical procedures
Vacuum extractor delivery	0/300 (0%)	0	0/300 (0%)	0	0/300 (0%)	0	1/270 (0.4%)	1	0/274 (0%)	0	0/259 (0%)	0
Other (Not Including Serious) Adverse Events
	Maternal Chloroquine Prophylaxis		Maternal Chloroquine IPT		Maternal SP IPT		Infant Chloroquine Prophylaxis		Infant Chloroquine IPT		Infant SP IPT
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	255/300 (85%)		251/300 (83.7%)		234/300 (78%)		195/270 (72.2%)		186/274 (67.9%)		171/259 (66%)
Blood and lymphatic system disorders
Anaemia	12/300 (4%)	14	20/300 (6.7%)	21	17/300 (5.7%)	17	0/270 (0%)	0	0/274 (0%)	0	0/259 (0%)	0
Cardiac disorders
Palpitations	16/300 (5.3%)	16	19/300 (6.3%)	21	8/300 (2.7%)	8	0/270 (0%)	0	0/274 (0%)	0	0/259 (0%)	0
Eye disorders
Conjunctivitis	3/300 (1%)	3	1/300 (0.3%)	1	7/300 (2.3%)	7	22/270 (8.1%)	22	27/274 (9.9%)	28	17/259 (6.6%)	17
Gastrointestinal disorders
Abdominal pain	78/300 (26%)	92	73/300 (24.3%)	90	62/300 (20.7%)	77	4/270 (1.5%)	4	2/274 (0.7%)	2	2/259 (0.8%)	2
Diarrhoea	36/300 (12%)	39	28/300 (9.3%)	29	16/300 (5.3%)	17	9/270 (3.3%)	9	6/274 (2.2%)	6	5/259 (1.9%)	5
Nausea	3/300 (1%)	3	17/300 (5.7%)	20	2/300 (0.7%)	2	0/270 (0%)	0	0/274 (0%)	0	0/259 (0%)	0
Vomiting	32/300 (10.7%)	37	63/300 (21%)	75	16/300 (5.3%)	17	3/270 (1.1%)	3	6/274 (2.2%)	6	4/259 (1.5%)	4
General disorders
Pain	16/300 (5.3%)	18	26/300 (8.7%)	30	21/300 (7%)	21	0/270 (0%)	0	0/274 (0%)	0	0/259 (0%)	0
Pyrexia	7/300 (2.3%)	8	13/300 (4.3%)	14	6/300 (2%)	6	18/270 (6.7%)	19	15/274 (5.5%)	15	12/259 (4.6%)	12
Infections and infestations
Gastroenteritis	20/300 (6.7%)	23	10/300 (3.3%)	12	18/300 (6%)	19	9/270 (3.3%)	10	9/274 (3.3%)	9	3/259 (1.2%)	3
Tonsillitis	23/300 (7.7%)	25	12/300 (4%)	13	12/300 (4%)	15	0/270 (0%)	0	0/274 (0%)	0	0/259 (0%)	0
Upper respiratory tract infection	90/300 (30%)	113	65/300 (21.7%)	70	73/300 (24.3%)	82	136/270 (50.4%)	172	124/274 (45.3%)	154	118/259 (45.6%)	152
Urinary tract infection	25/300 (8.3%)	29	27/300 (9%)	28	27/300 (9%)	28	0/270 (0%)	0	0/274 (0%)	0	0/259 (0%)	0
Vulvovaginal candidiasis	11/300 (3.7%)	13	17/300 (5.7%)	18	13/300 (4.3%)	14	0/270 (0%)	0	0/274 (0%)	0	0/259 (0%)	0
Bronchiolitis	1/300 (0.3%)	1	0/300 (0%)	0	0/300 (0%)	0	10/270 (3.7%)	10	7/274 (2.6%)	7	17/259 (6.6%)	18
Impetigo	1/300 (0.3%)	1	0/300 (0%)	0	0/300 (0%)	0	4/270 (1.5%)	4	3/274 (1.1%)	3	14/259 (5.4%)	15
Nasopharyngitis	15/300 (5%)	15	7/300 (2.3%)	7	15/300 (5%)	15	18/270 (6.7%)	19	19/274 (6.9%)	19	18/259 (6.9%)	18
Pneumonia	12/300 (4%)	13	5/300 (1.7%)	5	4/300 (1.3%)	4	8/270 (3%)	8	15/274 (5.5%)	15	11/259 (4.2%)	11
Respiratory tract infection	13/300 (4.3%)	13	6/300 (2%)	6	4/300 (1.3%)	4	19/270 (7%)	19	29/274 (10.6%)	31	17/259 (6.6%)	18
Rhinitis	12/300 (4%)	12	8/300 (2.7%)	8	14/300 (4.7%)	16	15/270 (5.6%)	16	16/274 (5.8%)	16	12/259 (4.6%)	13
Skin bacterial infection	2/300 (0.7%)	2	0/300 (0%)	0	1/300 (0.3%)	1	22/270 (8.1%)	25	15/274 (5.5%)	15	19/259 (7.3%)	19
Investigations
Blood pressure increased	12/300 (4%)	12	12/300 (4%)	12	20/300 (6.7%)	20	0/270 (0%)	0	0/274 (0%)	0	0/259 (0%)	0
Musculoskeletal and connective tissue disorders
Back pain	21/300 (7%)	25	19/300 (6.3%)	21	16/300 (5.3%)	16	0/270 (0%)	0	0/274 (0%)	0	0/259 (0%)	0
Musculoskeletal pain	79/300 (26.3%)	88	75/300 (25%)	95	56/300 (18.7%)	70	0/270 (0%)	0	1/274 (0.4%)	1	0/259 (0%)	0
Nervous system disorders
Dizziness	16/300 (5.3%)	16	62/300 (20.7%)	75	12/300 (4%)	12	0/270 (0%)	0	0/274 (0%)	0	0/259 (0%)	0
Headache	88/300 (29.3%)	113	76/300 (25.3%)	96	76/300 (25.3%)	89	0/270 (0%)	0	0/274 (0%)	0	0/259 (0%)	0
Pregnancy, puerperium and perinatal conditions
Gestational hypertension	24/300 (8%)	24	28/300 (9.3%)	28	26/300 (8.7%)	27	0/270 (0%)	0	0/274 (0%)	0	0/259 (0%)	0
Prolonged labour	20/300 (6.7%)	20	25/300 (8.3%)	25	22/300 (7.3%)	22	0/270 (0%)	0	0/274 (0%)	0	0/259 (0%)	0
Renal and urinary disorders
Proteinuria	11/300 (3.7%)	11	24/300 (8%)	24	15/300 (5%)	15	0/270 (0%)	0	0/274 (0%)	0	0/259 (0%)	0
Vascular disorders
Hypotension	12/300 (4%)	15	20/300 (6.7%)	24	12/300 (4%)	16	0/270 (0%)	0	0/274 (0%)	0	0/259 (0%)	0

Limitations/Caveats

The observed placental malaria rate was lower than expected causing the study to be under powered. After review of a futility analysis, the Sponsor and DSMB recommended allowing the study to conclude as planned and not to increase the sample size.

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.