PROMOTE-BC1: Reducing the Burden of Malaria in HIV-uninfected Pregnant Women and Infants

• Sponsor: Grant Dorsey, M.D, Ph.D. (Other)
• Overall Status: Completed
• CT.gov ID: NCT02163447
• Collaborator: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH)
• Enrollment: 300
• Location: 1
• Arms: 5
• Actual Duration (Months): 46.7
• Patients Per Site Per Month: 6.4

Study Details

Study Description

Brief Summary

This will be a double-blinded randomized controlled phase III trial of 300 HIV uninfected pregnant women and the children born to them. The study interventions will be divided into two phases. In the first phase, HIV uninfected women at 12-20 weeks gestation will be randomized in equal proportions to one of three intermittent preventive therapy in pregnancy (IPTp) treatment arms: 1) 3 doses of sulfadoxine-pyrimethamine (SP), 2) 3 doses of dihydroartemisinin-piperaquine (DP), or 3) monthly DP. All three interventions arms will have either SP or DP placebo to ensure adequate blinding is achieved. Follow-up for the pregnant women will end approximately 6 weeks after giving birth. In the second phase of the study, all children born to mothers enrolled in the study will be followed from birth until they reach 36 months of age. Children born to mothers randomized to receive 3 doses of SP during pregnancy will receive DP every 3 months between 2-24 months of age. Children born to mothers randomized to receive 3 doses of DP or monthly DP during pregnancy will receive either DP every 3 months or monthly DP between 2-24 months of age. To ensure adequate blinding, children who will receive DP every 3 months will be given DP placebo during the months they will not be taking DP. Children will then be followed an additional year between 24-36 months of age following the interventions. We will test the hypothesis that IPT with DP will significantly reduce the burden of malaria in pregnancy and infancy and improve the development of naturally acquired antimalarial immunity.

Condition or Disease	Intervention/Treatment	Phase
Malaria	Drug: Monthly dihydroartemisinin-piperaquine (DP) for adult women during pregnancy; Drug: 3 dose dihydroartemisinin-piperaquine (DP) for adult women during pregnancy; Drug: 3 dose sulfadoxine-pyrimethamine (SP) for adult women during pregnancy; Drug: Monthly dihydroartemisinin-piperaquine (DP) for infants; Drug: 3-monthly dihydroartemisinin-piperaquine (DP) for infants	Phase 3

Detailed Description

Pregnant women will be scheduled to be seen in the clinic every 4 weeks during their pregnancy and 6 weeks following delivery. In addition, pregnant women will be instructed to come to the study clinic for all their medical care and avoid the use of any outside medications. Children will be scheduled to be seen in the clinic every 4 weeks and parents /guardians of children will be instructed to bring their child to the study clinic for all medical care and avoid the use of any outside medications. The study clinic will remain open 7 days a week from 8 a.m. to 5 p.m.

Each time a study participant is seen in the clinic a standardized history and physical exam will be performed. Patients who are febrile (tympanic temperature > 3 8.0˚C) or report history of fever in the past 24 hours will have blood obtained by finger prick for a thick blood smear. If the thick blood smear is positive, the patient will be diagnosed with malaria. If the thick blood smear is negative, the patient will be managed by study physicians for a non-malarial febrile illness. If the patient is afebrile and does not report a recent fever, a thick blood smear will not be obtained, except when following routine testing schedules.

Routine assessments will be done in the clinic every 4 weeks for both pregnant women and children. Pregnant women and children will receive standards of care as designated in the Uganda MOH guidelines. Routine care in children will use Integrated Management of Childhood Illness (IMCI) guidelines. During routine assessments subjects will be asked about visits to outside health facilities and the use of any medications outside the study protocol. Standardized assessment of adherence will also be done for study drugs administered at home and Insecticide Treated Net use. A routine history and physical exam will be performed using a standardized clinical assessment form. Blood will be collected by finger prick for thick smear, collection of plasma for PK studies, and filter paper samples. Phlebotomy for routine laboratory tests (CBC and ALT) to monitor for potential adverse events from study medications and for immunology studies will be performed every 8 weeks in pregnant women and every 16 weeks in children. Non malaria screening will also include stool ova and parasite examination, circulating filarial antigens (by ICT card for Wucheria), and blood smear for microfilaremia (including Mansonella perstans) using Knott's technique. For pregnant women and children 2-24 months of age, study drugs will be administered at the time of each routine visit.

Study Design

• Study Type: Interventional
• Actual Enrollment: 300 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Reducing the Burden of Malaria in HIV-uninfected Pregnant Women and Infants (PROMOTE Birth Cohort 1)
• Actual Study Start Date: Jun 23, 2014
• Actual Primary Completion Date: May 14, 2018
• Actual Study Completion Date: May 14, 2018

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 3 dose SP pregnancy / 3 monthly DP infancy Women will be given SP (3 full strength tabs, 500 mg/25 mg) 3 times during pregnancy at 20, 28, and 36 weeks gestational age. In addition, placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two pills on day 1 (SP and placebo, DP and placebo, or two placebos) followed by one pill on days 2 and 3 (DP or placebo). Two placebos will be used, one that mimics the appearance of SP and one that mimics the appearance of DP. Infants will be given DP (once a day for 3 consecutive days using weight-based guidelines) every 12 weeks between 8 and 104 weeks of age. Infants randomized to receive DP every 12 weeks will receive placebo mimicking the dosing of DP every 4 weeks when they are not receiving study drug.	Drug: 3 dose sulfadoxine-pyrimethamine (SP) for adult women during pregnancy; Other Names: Kamsidar (KPI) ; Drug: 3-monthly dihydroartemisinin-piperaquine (DP) for infants; Other Names: Duo-Cotexin (Holley-Cotec)
Active Comparator: 3 dose DP pregnancy / 3 monthly DP infancy Women will be given DP (3 full strength tabs, 40 mg/320 mg, given once a day for 3 consecutive days) 3 times during pregnancy at 20, 28, and 36 weeks gestational age. In addition, placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two pills on day 1 (SP and placebo, DP and placebo, or two placebos) followed by one pill on days 2 and 3 (DP or placebo). Two placebos will be used, one that mimics the appearance of SP and one that mimics the appearance of DP. Infants will be given DP (once a day for 3 consecutive days using weight-based guidelines) every 12 weeks between 8 and 104 weeks of age. Infants randomized to receive DP every 12 weeks will receive placebo mimicking the dosing of DP every 4 weeks when they are not receiving study drug.	Drug: 3 dose dihydroartemisinin-piperaquine (DP) for adult women during pregnancy; Other Names: Duo-Cotexin (Holley-Cotec) ; Drug: 3-monthly dihydroartemisinin-piperaquine (DP) for infants; Other Names: Duo-Cotexin (Holley-Cotec)
Active Comparator: 3 dose DP pregnancy / monthly DP infancy Women will be given DP (3 full strength tabs, 40 mg/320 mg, given once a day for 3 consecutive days) 3 times during pregnancy at 20, 28, and 36 weeks gestational age. In addition, placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two pills on day 1 (SP and placebo, DP and placebo, or two placebos) followed by one pill on days 2 and 3 (DP or placebo). Two placebos will be used, one that mimics the appearance of SP and one that mimics the appearance of DP. Infants will be given DP (once a day for 3 consecutive days using weight-based guidelines) every 4 weeks between 8 and 104 weeks of age.	Drug: 3 dose dihydroartemisinin-piperaquine (DP) for adult women during pregnancy; Other Names: Duo-Cotexin (Holley-Cotec) ; Drug: Monthly dihydroartemisinin-piperaquine (DP) for infants; Other Names: Duo-Cotexin (Holley-Cotec)
Active Comparator: monthly DP pregnancy / 3 monthly DP infancy Women will be given DP (3 full strength tabs, 40 mg/320 mg, given once a day for 3 consecutive days) every 4 weeks during pregnancy. In addition, placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two pills on day 1 (SP and placebo, DP and placebo, or two placebos) followed by one pill on days 2 and 3 (DP or placebo). Two placebos will be used, one that mimics the appearance of SP and one that mimics the appearance of DP. Infants will be given DP (once a day for 3 consecutive days) every 12 weeks between 8 and 104 weeks of age. Infants randomized to receive DP every 12 weeks will receive placebo mimicking the dosing of DP every 4 weeks when they are not receiving study drug.	Drug: Monthly dihydroartemisinin-piperaquine (DP) for adult women during pregnancy; Other Names: Duo-Cotexin (Holley-Cotec) ; Drug: 3-monthly dihydroartemisinin-piperaquine (DP) for infants; Other Names: Duo-Cotexin (Holley-Cotec)
Active Comparator: monthly DP pregnancy / monthly DP infancy Women will be given DP (3 full strength tabs, 40 mg/320 mg, given once a day for 3 consecutive days) every 4 weeks during pregnancy. In addition, placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two pills on day 1 (SP and placebo, DP and placebo, or two placebos) followed by one pill on days 2 and 3 (DP or placebo). Two placebos will be used, one that mimics the appearance of SP and one that mimics the appearance of DP. Infants will be given DP (once a day for 3 consecutive days) every 4 weeks between 8 and 104 weeks of age.	Drug: Monthly dihydroartemisinin-piperaquine (DP) for adult women during pregnancy; Other Names: Duo-Cotexin (Holley-Cotec) ; Drug: Monthly dihydroartemisinin-piperaquine (DP) for infants; Other Names: Duo-Cotexin (Holley-Cotec)

Outcome Measures

Primary Outcome Measures

1. Prevalence of Placental Malaria [Delivery]

   Prevalence of placental malaria based on placental histopathology dichotomized into any evidence of placental infection (parasites or pigment) vs. no evidence and by histopathology as a categorical variable based on Rogerson et al criteria.

2. Incidence of Malaria in Pregnant Women [Time at risk will begin after first dose of study drug and will end when study participants deliver or early study termination]

   Incidence of malaria, defined as the number of incident episodes per time at risk. Incident cases will include all treatments for malaria not proceeded by another treatment in the previous 14 days.

3. Incidence of Malaria in Infants [Time at risk will begin at birth and will end when study participants reaches 24 months of age or early study termination (if prior to 24 months of age)]

   Incident cases will include all treatments for malaria not proceeded by another treatment in the previous 14 days. The study investigators will test the hypotheses that A) infants born to mothers randomized to receive IPTp with 3 dose DP or monthly DP will have a lower incidence of malaria during the first 24 months of life compared to infants born to mothers who were randomized to receive IPTp with 3 doses of SP, and, B) infants randomized to receive monthly DP between 2-24 months of age will have a lower incidence of malaria between 24-36 months of age after the intervention is stopped compared to infants randomized q 3 monthly DP between 2-24 months of age.

4. Incidence of Malaria in Infants [Time at risk will begin at 24 months of age and will end when study participants reaches 36 months of age or termination]

   Incident cases will include all treatments for malaria not proceeded by another treatment in the previous 14 days. The study investigators will test the hypotheses that A) infants born to mothers randomized to receive IPTp with 3 dose DP or monthly DP will have a lower incidence of malaria during the first 24 months of life compared to infants born to mothers who were randomized to receive IPTp with 3 doses of SP, and, B) infants randomized to receive monthly DP between 2-24 months of age will have a lower incidence of malaria between 24-36 months of age after the intervention is stopped compared to infants randomized q 3 monthly DP between 2-24 months of age.

Secondary Outcome Measures

1. Number of Participants With Blood Samples Positive for Parasites by Microscopy or LAMP [Delivery]

   Prevalence of placental blood samples positive for parasites by microscopy or LAMP

2. Number of Participants With Maternal Blood Samples Positive for Parasites by Microscopy and LAMP at Delivery [At delivery]

   Prevalence of maternal parasitemia at delivery by microscopy and LAMP

3. Number of Participants With One or More Birth Outcomes: Congenital Malformations, Spontaneous Abortion, LBW (<2500g), Still Birth, Pre-term Delivery [Delivery]

   Congenital malformations, spontaneous abortion, LBW (<2500g), still birth, pre-term delivery

4. Prevalence of Anemia in Pregnant Women [After first dose of study drugs up to delivery or early termination]

   Prevalence of routine hemoglobin measurements < 11 g/dL

5. Incidence of Complicated Malaria in Infants [Birth up to 24 months of age or early study termination]

   Any treatment for malaria meeting criteria for severe malaria or danger signs

6. Incidence of Hospital Admissions in Infants [Birth up to 24 months of age or early study termination]

   Admission to a hospital for pediatric inpatient care for any reason

7. Prevalence of Gametocytemia in Pregnant Women [Gestational age between 12-20 weeks (at study entry) up to delivery]

   Proportion of urgent blood smears positive for gametocytes

8. Prevalence of Parasitemia in Infants [Birth up to 24 months of age or early study termination]

   Proportion of routine monthly samples positive for parasites by LAMP. Proportion of routine samples (LAMP or blood smears) positive for asexual parasites.

9. Prevalence of Parasitemia at the Time of Monthly Routine Visits During Pregnancy [After first dose of study drug through delivery or early termination]

   Detection of malaria parasites by LAMP during pregnancy

10. Prevalence of Gametocytemia in Infants [Birth up to 24 months of age or early study termination]

    Proportion of routine blood smears positive for gametocytes

Eligibility Criteria

Criteria

• Ages Eligible for Study: 16 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. Pregnancy confirmed by positive urine pregnancy test or intrauterine pregnancy by ultrasound

2. Estimated gestational age between 12-20 weeks

3. Confirmed to be HIV uninfected by rapid test

4. 16 years of age or older

5. Residency within 30km of the study clinic

6. Provision of informed consent by the pregnant woman for herself and her unborn child

7. Agreement to come to the study clinic for any febrile episode or other illness and avoid medications given outside the study protocol

8. Plan to deliver in the hospital

Exclusion Criteria:

1. History of serious adverse event to SP or DP

2. Active medical problem requiring inpatient evaluation at the time of screening

3. Intention of moving more than 30km from the study clinic

4. Chronic medical condition requiring frequent medical attention

5. Prior SP preventive therapy or any other antimalarial therapy during this pregnancy

6. Early or active labor (documented by cervical change with uterine contractions)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	IDRC Research Clinic -Tororo District Hospital	Tororo		Uganda

Sponsors and Collaborators

• Grant Dorsey, M.D, Ph.D.
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

• Principal Investigator: Grant Dorsey, MD, PhD, University of California, San Francisco
• Principal Investigator: Diane V Havlir, MD, University of California, San Francisco
• Principal Investigator: Moses Kamya, MBChB, MMed, PhD, Makerere University; Infectious Diseases Research Collaboration

Study Documents (Full-Text)

• Statistical Analysis Plan - May 8, 2015
• Study Protocol - Oct 25, 2017

More Information

Publications

None provided.

• Responsible Party: Grant Dorsey, M.D, Ph.D., Professor, University of California, San Francisco
• ClinicalTrials.gov Identifier: NCT02163447
• Other Study ID Numbers: PROMOTE-BC1; P01HD059454
• First Posted: Jun 13, 2014
• Last Update Posted: Oct 20, 2020
• Last Verified: Oct 1, 2020

• Keywords provided by Grant Dorsey, M.D, Ph.D., Professor, University of California, San Francisco: Chemoprevention; Malaria; Uganda; Sulfadoxine-pyrimethamine; Dihydroartemisinin-piperaquine
• Additional relevant MeSH terms: Malaria; Pyrimethamine; Piperaquine; Sulfadoxine; Fanasil, pyrimethamine drug combination; Artenimol; Artemisinins

Study Results

Participant Flow

Arm/Group Title	Mothers - 3 Dose SP	Mothers - 3 Dose DP	Mothers - Monthly DP
Arm/Group Description	Sulfadoxine-Pyrimethamine 500mg/25mg	Dihydrioartemisinin-Piperaquine 40mg/320mg	Dihydroartemisinin-Piperaquine 20mg/160mg
Period Title: Overall Study
STARTED	106	94	100
Infants Born	101	93	100
COMPLETED	100	88	97
NOT COMPLETED	6	6	3

Baseline Characteristics

Arm/Group Title	Mothers - 3 Dose SP	Mothers - 3 Dose DP	Mothers - Monthly DP	Total
Arm/Group Description	Sulfadoxine-Pyrimethamine 500mg/25mg	Dihydrioartemisinin-Piperaquine 40mg/320mg	Dihydroartemisinin-Piperaquine 20mg/160mg	Total of all reporting groups
Overall Participants	106	94	100	300
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	21.3 (3.6)	22.2 (4.3)	22.6 (4.0)	22.0 (4.0)
Sex: Female, Male (Count of Participants)
Female	106 100%	94 100%	100 100%	300 100%
Male	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	106 100%	94 100%	100 100%	300 100%
White	0 0%	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Gestation (weeks) (Count of Participants)
12 to 16 wk	75 70.8%	65 69.1%	67 67%	207 69%
> 16 to 20 wk	31 29.2%	29 30.9%	33 33%	93 31%
Gravidity (Count of Participants)
1	42 39.6%	33 35.1%	36 36%	111 37%
2	32 30.2%	28 29.8%	28 28%	88 29.3%
>= 3	32 30.2%	33 35.1%	36 36%	101 33.7%
Bed-net ownership (Count of Participants)
None	13 12.3%	8 8.5%	9 9%	30 10%
Untreated Net	1 0.9%	6 6.4%	2 2%	9 3%
Long lasting insecticide- treated net	92 86.8%	80 85.1%	89 89%	261 87%
Household wealth index (Count of Participants)
Lowest third	38 35.8%	29 30.9%	33 33%	100 33.3%
Middle third	32 30.2%	37 39.4%	31 31%	100 33.3%
Highest third	36 34%	28 29.8%	36 36%	100 33.3%
Weight (kg) (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	55.4 (6.8)	55.6 (7.0)	55.5 (7.5)	55.5 (7.1)
Height (cm) (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	162.8 (6.8)	162.5 (6.7)	162.3 (7.7)	162.5 (7.1)
White blood cells per mm^3 (cells per mm^3) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cells per mm^3]	6036 (2070)	6279 (1713)	6040 (1572)	6113 (1802)
Neutrophil cells per mm^3 (cells per mm^3) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cells per mm^3]	3330 (1477)	3558 (1304)	3351 (1175)	3409 (1327)
Platelet cells per mm^3 (cells per mm^3) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cells per mm^3]	198906 (60665)	201809 (67358)	195840 (59593)	198793 (62332)
Hemoglobin level g/dL (g/DL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [g/DL]	11.8 (1.5)	11.9 (1.1)	12.0 (1.4)	11.9 (1.3)
Alanine aminotransferase level IU/L (IU/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [IU/L]	15.4 (7.5)	14.9 (5.8)	14.7 (5.6)	15.0 (6.4)
Detection of malaria parasites by LAMP (Count of Participants)
Yes	59 55.7%	55 58.5%	57 57%	171 57%
No	47 44.3%	38 40.4%	43 43%	128 42.7%
No sample collected	0 0%	1 1.1%	0 0%	1 0.3%

Outcome Measures

1. Primary Outcome

Title	Prevalence of Placental Malaria
Description	Prevalence of placental malaria based on placental histopathology dichotomized into any evidence of placental infection (parasites or pigment) vs. no evidence and by histopathology as a categorical variable based on Rogerson et al criteria.
Time Frame	Delivery

Outcome Measure Data

Analysis Population Description

Only women who delivered and had histopathology results were analyzed. 2 women in 3 Dose SP and 1 woman in monthly DP arms completed the study but did not have histopathology results.

Arm/Group Title	Mothers - 3 Dose SP	Mothers - 3 Dose DP	Mothers - Monthly DP
Arm/Group Description	Women will be given SP (3 full strength tabs, 500 mg/25 mg) 3 times during pregnancy at 20, 28, and 36 weeks gestational age. In addition, placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two pills on day 1 (SP and placebo, DP and placebo, or two placebos) followed by one pill on days 2 and 3 (DP or placebo). Two placebos will be used, one that mimics the appearance of SP and one that mimics the appearance of DP. Infants will be given DP (once a day for 3 consecutive days using weight-based guidelines) every 12 weeks between 8 and 104 weeks of age. Infants randomized to receive DP every 12 weeks will receive placebo mimicking the dosing of DP every 4 weeks when they are not receiving study drug. 3 dose sulfadoxine-pyrimethamine (SP) for adult women during pregnancy 3-monthly dihydroartemisinin-piperaquine (DP) for infants	Women will be given DP (3 full strength tabs, 40 mg/320 mg, given once a day for 3 consecutive days) 3 times during pregnancy at 20, 28, and 36 weeks gestational age. In addition, placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two pills on day 1 (SP and placebo, DP and placebo, or two placebos) followed by one pill on days 2 and 3 (DP or placebo). Two placebos will be used, one that mimics the appearance of SP and one that mimics the appearance of DP. Infants will be given DP (once a day for 3 consecutive days using weight-based guidelines) every 12 weeks between 8 and 104 weeks of age. Infants randomized to receive DP every 12 weeks will receive placebo mimicking the dosing of DP every 4 weeks when they are not receiving study drug. 3 dose dihydroartemisinin-piperaquine (DP) for adult women during pregnancy 3-monthly dihydroartemisinin-piperaquine (DP) for infants	Women will be given DP (3 full strength tabs, 40 mg/320 mg, given once a day for 3 consecutive days) 3 times during pregnancy at 20, 28, and 36 weeks gestational age. In addition, placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two pills on day 1 (SP and placebo, DP and placebo, or two placebos) followed by one pill on days 2 and 3 (DP or placebo). Two placebos will be used, one that mimics the appearance of SP and one that mimics the appearance of DP. Infants will be given DP (once a day for 3 consecutive days using weight-based guidelines) every 4 weeks between 8 and 104 weeks of age. 3 dose dihydroartemisinin-piperaquine (DP) for adult women during pregnancy Monthly dihydroartemisinin-piperaquine (DP) for infants
Measure Participants	98	88	96
Count of Participants [Participants]	49 46.2%	30 31.9%	26 26%

2. Primary Outcome

Title	Incidence of Malaria in Pregnant Women
Description	Incidence of malaria, defined as the number of incident episodes per time at risk. Incident cases will include all treatments for malaria not proceeded by another treatment in the previous 14 days.
Time Frame	Time at risk will begin after first dose of study drug and will end when study participants deliver or early study termination

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mothers - 3 Dose SP	Mothers - 3 Dose DP	Mothers - Monthly DP
Arm/Group Description	Sulfadoxine-Pyrimethamine 500mg/25mg	Dihydrioartemisinin-Piperaquine 40mg/320mg	Dihydroartemisinin-Piperaquine 20mg/160mg
Measure Participants	106	94	100
Number [events per person years]	0.95	0.31	0

3. Primary Outcome

Title	Incidence of Malaria in Infants
Description	Incident cases will include all treatments for malaria not proceeded by another treatment in the previous 14 days. The study investigators will test the hypotheses that A) infants born to mothers randomized to receive IPTp with 3 dose DP or monthly DP will have a lower incidence of malaria during the first 24 months of life compared to infants born to mothers who were randomized to receive IPTp with 3 doses of SP, and, B) infants randomized to receive monthly DP between 2-24 months of age will have a lower incidence of malaria between 24-36 months of age after the intervention is stopped compared to infants randomized q 3 monthly DP between 2-24 months of age.
Time Frame	Time at risk will begin at birth and will end when study participants reaches 24 months of age or early study termination (if prior to 24 months of age)

Outcome Measure Data

Analysis Population Description

All live births

Arm/Group Title	3 Dose SP Pregnancy / 3 Monthly DP Infancy	3 Dose DP Pregnancy / 3 Monthly DP Infancy	3 Dose DP Pregnancy / Monthly DP Infancy	Monthly DP Pregnancy / 3 Monthly DP Infancy	Monthly DP Pregnancy / Monthly DP Infancy
Arm/Group Description	Women will be given SP (3 full strength tabs, 500 mg/25 mg) 3 times during pregnancy at 20, 28, and 36 weeks gestational age. In addition, placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two pills on day 1 (SP and placebo, DP and placebo, or two placebos) followed by one pill on days 2 and 3 (DP or placebo). Two placebos will be used, one that mimics the appearance of SP and one that mimics the appearance of DP. Infants will be given DP (once a day for 3 consecutive days using weight-based guidelines) every 12 weeks between 8 and 104 weeks of age. Infants randomized to receive DP every 12 weeks will receive placebo mimicking the dosing of DP every 4 weeks when they are not receiving study drug. 3 dose sulfadoxine-pyrimethamine (SP) for adult women during pregnancy 3-monthly dihydroartemisinin-piperaquine (DP) for infants	Women will be given DP (3 full strength tabs, 40 mg/320 mg, given once a day for 3 consecutive days) 3 times during pregnancy at 20, 28, and 36 weeks gestational age. In addition, placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two pills on day 1 (SP and placebo, DP and placebo, or two placebos) followed by one pill on days 2 and 3 (DP or placebo). Two placebos will be used, one that mimics the appearance of SP and one that mimics the appearance of DP. Infants will be given DP (once a day for 3 consecutive days using weight-based guidelines) every 12 weeks between 8 and 104 weeks of age. Infants randomized to receive DP every 12 weeks will receive placebo mimicking the dosing of DP every 4 weeks when they are not receiving study drug. 3 dose dihydroartemisinin-piperaquine (DP) for adult women during pregnancy 3-monthly dihydroartemisinin-piperaquine (DP) for infants	Women will be given DP (3 full strength tabs, 40 mg/320 mg, given once a day for 3 consecutive days) 3 times during pregnancy at 20, 28, and 36 weeks gestational age. In addition, placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two pills on day 1 (SP and placebo, DP and placebo, or two placebos) followed by one pill on days 2 and 3 (DP or placebo). Two placebos will be used, one that mimics the appearance of SP and one that mimics the appearance of DP. Infants will be given DP (once a day for 3 consecutive days using weight-based guidelines) every 4 weeks between 8 and 104 weeks of age. 3 dose dihydroartemisinin-piperaquine (DP) for adult women during pregnancy Monthly dihydroartemisinin-piperaquine (DP) for infants	Women will be given DP (3 full strength tabs, 40 mg/320 mg, given once a day for 3 consecutive days) every 4 weeks during pregnancy. In addition, placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two pills on day 1 (SP and placebo, DP and placebo, or two placebos) followed by one pill on days 2 and 3 (DP or placebo). Two placebos will be used, one that mimics the appearance of SP and one that mimics the appearance of DP. Infants will be given DP (once a day for 3 consecutive days) every 12 weeks between 8 and 104 weeks of age. Infants randomized to receive DP every 12 weeks will receive placebo mimicking the dosing of DP every 4 weeks when they are not receiving study drug. Monthly dihydroartemisinin-piperaquine (DP) for adult women during pregnancy 3-monthly dihydroartemisinin-piperaquine (DP) for infants	Women will be given DP (3 full strength tabs, 40 mg/320 mg, given once a day for 3 consecutive days) every 4 weeks during pregnancy. In addition, placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two pills on day 1 (SP and placebo, DP and placebo, or two placebos) followed by one pill on days 2 and 3 (DP or placebo). Two placebos will be used, one that mimics the appearance of SP and one that mimics the appearance of DP. Infants will be given DP (once a day for 3 consecutive days) every 4 weeks between 8 and 104 weeks of age. Monthly dihydroartemisinin-piperaquine (DP) for adult women during pregnancy Monthly dihydroartemisinin-piperaquine (DP) for infants
Measure Participants	101	44	49	48	52
Number [Events per person years]	0.26	0.30	0.00	0.43	0.03

4. Primary Outcome

Title	Incidence of Malaria in Infants
Description	Incident cases will include all treatments for malaria not proceeded by another treatment in the previous 14 days. The study investigators will test the hypotheses that A) infants born to mothers randomized to receive IPTp with 3 dose DP or monthly DP will have a lower incidence of malaria during the first 24 months of life compared to infants born to mothers who were randomized to receive IPTp with 3 doses of SP, and, B) infants randomized to receive monthly DP between 2-24 months of age will have a lower incidence of malaria between 24-36 months of age after the intervention is stopped compared to infants randomized q 3 monthly DP between 2-24 months of age.
Time Frame	Time at risk will begin at 24 months of age and will end when study participants reaches 36 months of age or termination

Outcome Measure Data

Analysis Population Description

All live births

Arm/Group Title	3 Dose SP Pregnancy / 3 Monthly DP Infancy	3 Dose DP Pregnancy / 3 Monthly DP Infancy	3 Dose DP Pregnancy / Monthly DP Infancy	Monthly DP Pregnancy / 3 Monthly DP Infancy	Monthly DP Pregnancy / Monthly DP Infancy
Arm/Group Description	Women will be given SP (3 full strength tabs, 500 mg/25 mg) 3 times during pregnancy at 20, 28, and 36 weeks gestational age. In addition, placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two pills on day 1 (SP and placebo, DP and placebo, or two placebos) followed by one pill on days 2 and 3 (DP or placebo). Two placebos will be used, one that mimics the appearance of SP and one that mimics the appearance of DP. Infants will be given DP (once a day for 3 consecutive days using weight-based guidelines) every 12 weeks between 8 and 104 weeks of age. Infants randomized to receive DP every 12 weeks will receive placebo mimicking the dosing of DP every 4 weeks when they are not receiving study drug. 3 dose sulfadoxine-pyrimethamine (SP) for adult women during pregnancy 3-monthly dihydroartemisinin-piperaquine (DP) for infants	Women will be given DP (3 full strength tabs, 40 mg/320 mg, given once a day for 3 consecutive days) 3 times during pregnancy at 20, 28, and 36 weeks gestational age. In addition, placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two pills on day 1 (SP and placebo, DP and placebo, or two placebos) followed by one pill on days 2 and 3 (DP or placebo). Two placebos will be used, one that mimics the appearance of SP and one that mimics the appearance of DP. Infants will be given DP (once a day for 3 consecutive days using weight-based guidelines) every 12 weeks between 8 and 104 weeks of age. Infants randomized to receive DP every 12 weeks will receive placebo mimicking the dosing of DP every 4 weeks when they are not receiving study drug. 3 dose dihydroartemisinin-piperaquine (DP) for adult women during pregnancy 3-monthly dihydroartemisinin-piperaquine (DP) for infants	Women will be given DP (3 full strength tabs, 40 mg/320 mg, given once a day for 3 consecutive days) 3 times during pregnancy at 20, 28, and 36 weeks gestational age. In addition, placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two pills on day 1 (SP and placebo, DP and placebo, or two placebos) followed by one pill on days 2 and 3 (DP or placebo). Two placebos will be used, one that mimics the appearance of SP and one that mimics the appearance of DP. Infants will be given DP (once a day for 3 consecutive days using weight-based guidelines) every 4 weeks between 8 and 104 weeks of age. 3 dose dihydroartemisinin-piperaquine (DP) for adult women during pregnancy Monthly dihydroartemisinin-piperaquine (DP) for infants	Women will be given DP (3 full strength tabs, 40 mg/320 mg, given once a day for 3 consecutive days) every 4 weeks during pregnancy. In addition, placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two pills on day 1 (SP and placebo, DP and placebo, or two placebos) followed by one pill on days 2 and 3 (DP or placebo). Two placebos will be used, one that mimics the appearance of SP and one that mimics the appearance of DP. Infants will be given DP (once a day for 3 consecutive days) every 12 weeks between 8 and 104 weeks of age. Infants randomized to receive DP every 12 weeks will receive placebo mimicking the dosing of DP every 4 weeks when they are not receiving study drug. Monthly dihydroartemisinin-piperaquine (DP) for adult women during pregnancy 3-monthly dihydroartemisinin-piperaquine (DP) for infants	Women will be given DP (3 full strength tabs, 40 mg/320 mg, given once a day for 3 consecutive days) every 4 weeks during pregnancy. In addition, placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two pills on day 1 (SP and placebo, DP and placebo, or two placebos) followed by one pill on days 2 and 3 (DP or placebo). Two placebos will be used, one that mimics the appearance of SP and one that mimics the appearance of DP. Infants will be given DP (once a day for 3 consecutive days) every 4 weeks between 8 and 104 weeks of age. Monthly dihydroartemisinin-piperaquine (DP) for adult women during pregnancy Monthly dihydroartemisinin-piperaquine (DP) for infants
Measure Participants	85	40	43	39	44
Number [Events per person years]	0.87	0.88	0.83	1.24	0.64

5. Secondary Outcome

Title	Number of Participants With Blood Samples Positive for Parasites by Microscopy or LAMP
Description	Prevalence of placental blood samples positive for parasites by microscopy or LAMP
Time Frame	Delivery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mothers - 3 Dose SP	Mothers - 3 Dose DP	Mothers - Monthly DP
Arm/Group Description	Women will be given SP (3 full strength tabs, 500 mg/25 mg) 3 times during pregnancy at 20, 28, and 36 weeks gestational age. In addition, placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two pills on day 1 (SP and placebo, DP and placebo, or two placebos) followed by one pill on days 2 and 3 (DP or placebo). Two placebos will be used, one that mimics the appearance of SP and one that mimics the appearance of DP. Infants will be given DP (once a day for 3 consecutive days using weight-based guidelines) every 12 weeks between 8 and 104 weeks of age. Infants randomized to receive DP every 12 weeks will receive placebo mimicking the dosing of DP every 4 weeks when they are not receiving study drug. 3 dose sulfadoxine-pyrimethamine (SP) for adult women during pregnancy 3-monthly dihydroartemisinin-piperaquine (DP) for infants	Women will be given DP (3 full strength tabs, 40 mg/320 mg, given once a day for 3 consecutive days) 3 times during pregnancy at 20, 28, and 36 weeks gestational age. In addition, placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two pills on day 1 (SP and placebo, DP and placebo, or two placebos) followed by one pill on days 2 and 3 (DP or placebo). Two placebos will be used, one that mimics the appearance of SP and one that mimics the appearance of DP. Infants will be given DP (once a day for 3 consecutive days using weight-based guidelines) every 12 weeks between 8 and 104 weeks of age. Infants randomized to receive DP every 12 weeks will receive placebo mimicking the dosing of DP every 4 weeks when they are not receiving study drug. 3 dose dihydroartemisinin-piperaquine (DP) for adult women during pregnancy 3-monthly dihydroartemisinin-piperaquine (DP) for infants	Women will be given DP (3 full strength tabs, 40 mg/320 mg, given once a day for 3 consecutive days) 3 times during pregnancy at 20, 28, and 36 weeks gestational age. In addition, placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two pills on day 1 (SP and placebo, DP and placebo, or two placebos) followed by one pill on days 2 and 3 (DP or placebo). Two placebos will be used, one that mimics the appearance of SP and one that mimics the appearance of DP. Infants will be given DP (once a day for 3 consecutive days using weight-based guidelines) every 4 weeks between 8 and 104 weeks of age. 3 dose dihydroartemisinin-piperaquine (DP) for adult women during pregnancy Monthly dihydroartemisinin-piperaquine (DP) for infants
Measure Participants	96	88	96
Micropscopic assessment of placental blood	5 4.7%	3 3.2%	0 0%
LAMP assessment of placental blood	19 17.9%	3 3.2%	2 2%

6. Secondary Outcome

Title	Number of Participants With Maternal Blood Samples Positive for Parasites by Microscopy and LAMP at Delivery
Description	Prevalence of maternal parasitemia at delivery by microscopy and LAMP
Time Frame	At delivery

Outcome Measure Data

Analysis Population Description

One observation in the monthly DP arm did not have results for microscopy; this outcome measure tests blood taken from the mother's arm (different from outcome measure 4 which tests blood taken from the placenta)

Arm/Group Title	Mothers - 3 Dose SP	Mothers - 3 Dose DP	Mothers - Monthly DP
Arm/Group Description	Sulfadoxine-Pyrimethamine 500mg/25mg	Dihydrioartemisinin-Piperaquine 40mg/320mg	Dihydroartemisinin-Piperaquine 20mg/160mg
Measure Participants	102	89	98
Microscopy	5 4.7%	1 1.1%	0 0%
LAMP	25 23.6%	3 3.2%	1 1%

7. Secondary Outcome

Title	Number of Participants With One or More Birth Outcomes: Congenital Malformations, Spontaneous Abortion, LBW (<2500g), Still Birth, Pre-term Delivery
Description	Congenital malformations, spontaneous abortion, LBW (<2500g), still birth, pre-term delivery
Time Frame	Delivery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mothers - 3 Dose SP	Mothers - 3 Dose DP	Mothers - Monthly DP
Arm/Group Description	Women will be given SP (3 full strength tabs, 500 mg/25 mg) 3 times during pregnancy at 20, 28, and 36 weeks gestational age. In addition, placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two pills on day 1 (SP and placebo, DP and placebo, or two placebos) followed by one pill on days 2 and 3 (DP or placebo). Two placebos will be used, one that mimics the appearance of SP and one that mimics the appearance of DP. Infants will be given DP (once a day for 3 consecutive days using weight-based guidelines) every 12 weeks between 8 and 104 weeks of age. Infants randomized to receive DP every 12 weeks will receive placebo mimicking the dosing of DP every 4 weeks when they are not receiving study drug. 3 dose sulfadoxine-pyrimethamine (SP) for adult women during pregnancy 3-monthly dihydroartemisinin-piperaquine (DP) for infants	Women will be given DP (3 full strength tabs, 40 mg/320 mg, given once a day for 3 consecutive days) 3 times during pregnancy at 20, 28, and 36 weeks gestational age. In addition, placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two pills on day 1 (SP and placebo, DP and placebo, or two placebos) followed by one pill on days 2 and 3 (DP or placebo). Two placebos will be used, one that mimics the appearance of SP and one that mimics the appearance of DP. Infants will be given DP (once a day for 3 consecutive days using weight-based guidelines) every 12 weeks between 8 and 104 weeks of age. Infants randomized to receive DP every 12 weeks will receive placebo mimicking the dosing of DP every 4 weeks when they are not receiving study drug. 3 dose dihydroartemisinin-piperaquine (DP) for adult women during pregnancy 3-monthly dihydroartemisinin-piperaquine (DP) for infants	Women will be given DP (3 full strength tabs, 40 mg/320 mg, given once a day for 3 consecutive days) 3 times during pregnancy at 20, 28, and 36 weeks gestational age. In addition, placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two pills on day 1 (SP and placebo, DP and placebo, or two placebos) followed by one pill on days 2 and 3 (DP or placebo). Two placebos will be used, one that mimics the appearance of SP and one that mimics the appearance of DP. Infants will be given DP (once a day for 3 consecutive days using weight-based guidelines) every 4 weeks between 8 and 104 weeks of age. 3 dose dihydroartemisinin-piperaquine (DP) for adult women during pregnancy Monthly dihydroartemisinin-piperaquine (DP) for infants
Measure Participants	102	89	98
Count of Participants [Participants]	19 17.9%	19 20.2%	9 9%

8. Secondary Outcome

Title	Prevalence of Anemia in Pregnant Women
Description	Prevalence of routine hemoglobin measurements < 11 g/dL
Time Frame	After first dose of study drugs up to delivery or early termination

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mothers - 3 Dose SP	Mothers - 3 Dose DP	Mothers - Monthly DP
Arm/Group Description	Women will be given SP (3 full strength tabs, 500 mg/25 mg) 3 times during pregnancy at 20, 28, and 36 weeks gestational age. In addition, placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two pills on day 1 (SP and placebo, DP and placebo, or two placebos) followed by one pill on days 2 and 3 (DP or placebo). Two placebos will be used, one that mimics the appearance of SP and one that mimics the appearance of DP. Infants will be given DP (once a day for 3 consecutive days using weight-based guidelines) every 12 weeks between 8 and 104 weeks of age. Infants randomized to receive DP every 12 weeks will receive placebo mimicking the dosing of DP every 4 weeks when they are not receiving study drug. 3 dose sulfadoxine-pyrimethamine (SP) for adult women during pregnancy 3-monthly dihydroartemisinin-piperaquine (DP) for infants	Women will be given DP (3 full strength tabs, 40 mg/320 mg, given once a day for 3 consecutive days) 3 times during pregnancy at 20, 28, and 36 weeks gestational age. In addition, placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two pills on day 1 (SP and placebo, DP and placebo, or two placebos) followed by one pill on days 2 and 3 (DP or placebo). Two placebos will be used, one that mimics the appearance of SP and one that mimics the appearance of DP. Infants will be given DP (once a day for 3 consecutive days using weight-based guidelines) every 12 weeks between 8 and 104 weeks of age. Infants randomized to receive DP every 12 weeks will receive placebo mimicking the dosing of DP every 4 weeks when they are not receiving study drug. 3 dose dihydroartemisinin-piperaquine (DP) for adult women during pregnancy 3-monthly dihydroartemisinin-piperaquine (DP) for infants	Women will be given DP (3 full strength tabs, 40 mg/320 mg, given once a day for 3 consecutive days) 3 times during pregnancy at 20, 28, and 36 weeks gestational age. In addition, placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two pills on day 1 (SP and placebo, DP and placebo, or two placebos) followed by one pill on days 2 and 3 (DP or placebo). Two placebos will be used, one that mimics the appearance of SP and one that mimics the appearance of DP. Infants will be given DP (once a day for 3 consecutive days using weight-based guidelines) every 4 weeks between 8 and 104 weeks of age. 3 dose dihydroartemisinin-piperaquine (DP) for adult women during pregnancy Monthly dihydroartemisinin-piperaquine (DP) for infants
Measure Participants	106	94	100
Measure hemoglobin measurements taken every 12wk	269	237	258
Number [hemoglobin measurements taken every 12wk]	94	72	61

9. Secondary Outcome

Title	Incidence of Complicated Malaria in Infants
Description	Any treatment for malaria meeting criteria for severe malaria or danger signs
Time Frame	Birth up to 24 months of age or early study termination

Outcome Measure Data

Analysis Population Description

All live births

Arm/Group Title	3 Dose SP Pregnancy / 3 Monthly DP Infancy	3 Dose DP Pregnancy / 3 Monthly DP Infancy	3 Dose DP Pregnancy / Monthly DP Infancy	Monthly DP Pregnancy / 3 Monthly DP Infancy	Monthly DP Pregnancy / Monthly DP Infancy
Arm/Group Description	Women will be given SP (3 full strength tabs, 500 mg/25 mg) 3 times during pregnancy at 20, 28, and 36 weeks gestational age. In addition, placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two pills on day 1 (SP and placebo, DP and placebo, or two placebos) followed by one pill on days 2 and 3 (DP or placebo). Two placebos will be used, one that mimics the appearance of SP and one that mimics the appearance of DP. Infants will be given DP (once a day for 3 consecutive days using weight-based guidelines) every 12 weeks between 8 and 104 weeks of age. Infants randomized to receive DP every 12 weeks will receive placebo mimicking the dosing of DP every 4 weeks when they are not receiving study drug. 3 dose sulfadoxine-pyrimethamine (SP) for adult women during pregnancy 3-monthly dihydroartemisinin-piperaquine (DP) for infants	Women will be given DP (3 full strength tabs, 40 mg/320 mg, given once a day for 3 consecutive days) 3 times during pregnancy at 20, 28, and 36 weeks gestational age. In addition, placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two pills on day 1 (SP and placebo, DP and placebo, or two placebos) followed by one pill on days 2 and 3 (DP or placebo). Two placebos will be used, one that mimics the appearance of SP and one that mimics the appearance of DP. Infants will be given DP (once a day for 3 consecutive days using weight-based guidelines) every 12 weeks between 8 and 104 weeks of age. Infants randomized to receive DP every 12 weeks will receive placebo mimicking the dosing of DP every 4 weeks when they are not receiving study drug. 3 dose dihydroartemisinin-piperaquine (DP) for adult women during pregnancy 3-monthly dihydroartemisinin-piperaquine (DP) for infants	Women will be given DP (3 full strength tabs, 40 mg/320 mg, given once a day for 3 consecutive days) 3 times during pregnancy at 20, 28, and 36 weeks gestational age. In addition, placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two pills on day 1 (SP and placebo, DP and placebo, or two placebos) followed by one pill on days 2 and 3 (DP or placebo). Two placebos will be used, one that mimics the appearance of SP and one that mimics the appearance of DP. Infants will be given DP (once a day for 3 consecutive days using weight-based guidelines) every 4 weeks between 8 and 104 weeks of age. 3 dose dihydroartemisinin-piperaquine (DP) for adult women during pregnancy Monthly dihydroartemisinin-piperaquine (DP) for infants	Women will be given DP (3 full strength tabs, 40 mg/320 mg, given once a day for 3 consecutive days) every 4 weeks during pregnancy. In addition, placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two pills on day 1 (SP and placebo, DP and placebo, or two placebos) followed by one pill on days 2 and 3 (DP or placebo). Two placebos will be used, one that mimics the appearance of SP and one that mimics the appearance of DP. Infants will be given DP (once a day for 3 consecutive days) every 12 weeks between 8 and 104 weeks of age. Infants randomized to receive DP every 12 weeks will receive placebo mimicking the dosing of DP every 4 weeks when they are not receiving study drug. Monthly dihydroartemisinin-piperaquine (DP) for adult women during pregnancy 3-monthly dihydroartemisinin-piperaquine (DP) for infants	Women will be given DP (3 full strength tabs, 40 mg/320 mg, given once a day for 3 consecutive days) every 4 weeks during pregnancy. In addition, placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two pills on day 1 (SP and placebo, DP and placebo, or two placebos) followed by one pill on days 2 and 3 (DP or placebo). Two placebos will be used, one that mimics the appearance of SP and one that mimics the appearance of DP. Infants will be given DP (once a day for 3 consecutive days) every 4 weeks between 8 and 104 weeks of age. Monthly dihydroartemisinin-piperaquine (DP) for adult women during pregnancy Monthly dihydroartemisinin-piperaquine (DP) for infants
Measure Participants	101	44	49	48	52
Number [Events per person years]	0.022	0.024	0.000	0.035	0.000

10. Secondary Outcome

Title	Incidence of Hospital Admissions in Infants
Description	Admission to a hospital for pediatric inpatient care for any reason
Time Frame	Birth up to 24 months of age or early study termination

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	3 Dose SP Pregnancy / 3 Monthly DP Infancy	3 Dose DP Pregnancy / 3 Monthly DP Infancy	3 Dose DP Pregnancy / Monthly DP Infancy	Monthly DP Pregnancy / 3 Monthly DP Infancy	Monthly DP Pregnancy / Monthly DP Infancy
Arm/Group Description	Women will be given SP (3 full strength tabs, 500 mg/25 mg) 3 times during pregnancy at 20, 28, and 36 weeks gestational age. In addition, placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two pills on day 1 (SP and placebo, DP and placebo, or two placebos) followed by one pill on days 2 and 3 (DP or placebo). Two placebos will be used, one that mimics the appearance of SP and one that mimics the appearance of DP. Infants will be given DP (once a day for 3 consecutive days using weight-based guidelines) every 12 weeks between 8 and 104 weeks of age. Infants randomized to receive DP every 12 weeks will receive placebo mimicking the dosing of DP every 4 weeks when they are not receiving study drug. 3 dose sulfadoxine-pyrimethamine (SP) for adult women during pregnancy 3-monthly dihydroartemisinin-piperaquine (DP) for infants	Women will be given DP (3 full strength tabs, 40 mg/320 mg, given once a day for 3 consecutive days) 3 times during pregnancy at 20, 28, and 36 weeks gestational age. In addition, placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two pills on day 1 (SP and placebo, DP and placebo, or two placebos) followed by one pill on days 2 and 3 (DP or placebo). Two placebos will be used, one that mimics the appearance of SP and one that mimics the appearance of DP. Infants will be given DP (once a day for 3 consecutive days using weight-based guidelines) every 12 weeks between 8 and 104 weeks of age. Infants randomized to receive DP every 12 weeks will receive placebo mimicking the dosing of DP every 4 weeks when they are not receiving study drug. 3 dose dihydroartemisinin-piperaquine (DP) for adult women during pregnancy 3-monthly dihydroartemisinin-piperaquine (DP) for infants	Women will be given DP (3 full strength tabs, 40 mg/320 mg, given once a day for 3 consecutive days) 3 times during pregnancy at 20, 28, and 36 weeks gestational age. In addition, placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two pills on day 1 (SP and placebo, DP and placebo, or two placebos) followed by one pill on days 2 and 3 (DP or placebo). Two placebos will be used, one that mimics the appearance of SP and one that mimics the appearance of DP. Infants will be given DP (once a day for 3 consecutive days using weight-based guidelines) every 4 weeks between 8 and 104 weeks of age. 3 dose dihydroartemisinin-piperaquine (DP) for adult women during pregnancy Monthly dihydroartemisinin-piperaquine (DP) for infants	Women will be given DP (3 full strength tabs, 40 mg/320 mg, given once a day for 3 consecutive days) every 4 weeks during pregnancy. In addition, placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two pills on day 1 (SP and placebo, DP and placebo, or two placebos) followed by one pill on days 2 and 3 (DP or placebo). Two placebos will be used, one that mimics the appearance of SP and one that mimics the appearance of DP. Infants will be given DP (once a day for 3 consecutive days) every 12 weeks between 8 and 104 weeks of age. Infants randomized to receive DP every 12 weeks will receive placebo mimicking the dosing of DP every 4 weeks when they are not receiving study drug. Monthly dihydroartemisinin-piperaquine (DP) for adult women during pregnancy 3-monthly dihydroartemisinin-piperaquine (DP) for infants	Women will be given DP (3 full strength tabs, 40 mg/320 mg, given once a day for 3 consecutive days) every 4 weeks during pregnancy. In addition, placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two pills on day 1 (SP and placebo, DP and placebo, or two placebos) followed by one pill on days 2 and 3 (DP or placebo). Two placebos will be used, one that mimics the appearance of SP and one that mimics the appearance of DP. Infants will be given DP (once a day for 3 consecutive days) every 4 weeks between 8 and 104 weeks of age. Monthly dihydroartemisinin-piperaquine (DP) for adult women during pregnancy Monthly dihydroartemisinin-piperaquine (DP) for infants
Measure Participants	101	44	49	48	52
Number [Events per person years]	0.043	0.036	0.089	0.082	0.043

11. Secondary Outcome

Title	Prevalence of Gametocytemia in Pregnant Women
Description	Proportion of urgent blood smears positive for gametocytes
Time Frame	Gestational age between 12-20 weeks (at study entry) up to delivery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mothers - 3 Dose SP	Mothers - 3 Dose DP	Mothers - Monthly DP
Arm/Group Description	Sulfadoxine-Pyrimethamine 500mg/25mg	Dihydrioartemisinin-Piperaquine 40mg/320mg	Dihydroartemisinin-Piperaquine 20mg/160mg
Measure Participants	106	94	100
Measure Blood smears	112	86	86
Number [Positive blood smears]	4	1	3

12. Secondary Outcome

Title	Prevalence of Parasitemia in Infants
Description	Proportion of routine monthly samples positive for parasites by LAMP. Proportion of routine samples (LAMP or blood smears) positive for asexual parasites.
Time Frame	Birth up to 24 months of age or early study termination

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	3 Dose SP Pregnancy / 3 Monthly DP Infancy	3 Dose DP Pregnancy / 3 Monthly DP Infancy	3 Dose DP Pregnancy / Monthly DP Infancy	Monthly DP Pregnancy / 3 Monthly DP Infancy	Monthly DP Pregnancy / Monthly DP Infancy
Arm/Group Description	Women will be given SP (3 full strength tabs, 500 mg/25 mg) 3 times during pregnancy at 20, 28, and 36 weeks gestational age. In addition, placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two pills on day 1 (SP and placebo, DP and placebo, or two placebos) followed by one pill on days 2 and 3 (DP or placebo). Two placebos will be used, one that mimics the appearance of SP and one that mimics the appearance of DP. Infants will be given DP (once a day for 3 consecutive days using weight-based guidelines) every 12 weeks between 8 and 104 weeks of age. Infants randomized to receive DP every 12 weeks will receive placebo mimicking the dosing of DP every 4 weeks when they are not receiving study drug. 3 dose sulfadoxine-pyrimethamine (SP) for adult women during pregnancy 3-monthly dihydroartemisinin-piperaquine (DP) for infants	Women will be given DP (3 full strength tabs, 40 mg/320 mg, given once a day for 3 consecutive days) 3 times during pregnancy at 20, 28, and 36 weeks gestational age. In addition, placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two pills on day 1 (SP and placebo, DP and placebo, or two placebos) followed by one pill on days 2 and 3 (DP or placebo). Two placebos will be used, one that mimics the appearance of SP and one that mimics the appearance of DP. Infants will be given DP (once a day for 3 consecutive days using weight-based guidelines) every 12 weeks between 8 and 104 weeks of age. Infants randomized to receive DP every 12 weeks will receive placebo mimicking the dosing of DP every 4 weeks when they are not receiving study drug. 3 dose dihydroartemisinin-piperaquine (DP) for adult women during pregnancy 3-monthly dihydroartemisinin-piperaquine (DP) for infants	Women will be given DP (3 full strength tabs, 40 mg/320 mg, given once a day for 3 consecutive days) 3 times during pregnancy at 20, 28, and 36 weeks gestational age. In addition, placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two pills on day 1 (SP and placebo, DP and placebo, or two placebos) followed by one pill on days 2 and 3 (DP or placebo). Two placebos will be used, one that mimics the appearance of SP and one that mimics the appearance of DP. Infants will be given DP (once a day for 3 consecutive days using weight-based guidelines) every 4 weeks between 8 and 104 weeks of age. 3 dose dihydroartemisinin-piperaquine (DP) for adult women during pregnancy Monthly dihydroartemisinin-piperaquine (DP) for infants	Women will be given DP (3 full strength tabs, 40 mg/320 mg, given once a day for 3 consecutive days) every 4 weeks during pregnancy. In addition, placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two pills on day 1 (SP and placebo, DP and placebo, or two placebos) followed by one pill on days 2 and 3 (DP or placebo). Two placebos will be used, one that mimics the appearance of SP and one that mimics the appearance of DP. Infants will be given DP (once a day for 3 consecutive days) every 12 weeks between 8 and 104 weeks of age. Infants randomized to receive DP every 12 weeks will receive placebo mimicking the dosing of DP every 4 weeks when they are not receiving study drug. Monthly dihydroartemisinin-piperaquine (DP) for adult women during pregnancy 3-monthly dihydroartemisinin-piperaquine (DP) for infants	Women will be given DP (3 full strength tabs, 40 mg/320 mg, given once a day for 3 consecutive days) every 4 weeks during pregnancy. In addition, placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two pills on day 1 (SP and placebo, DP and placebo, or two placebos) followed by one pill on days 2 and 3 (DP or placebo). Two placebos will be used, one that mimics the appearance of SP and one that mimics the appearance of DP. Infants will be given DP (once a day for 3 consecutive days) every 4 weeks between 8 and 104 weeks of age. Monthly dihydroartemisinin-piperaquine (DP) for adult women during pregnancy Monthly dihydroartemisinin-piperaquine (DP) for infants
Measure Participants	101	44	49	48	52
Measure Blood smears	2378	1082	1155	1099	1208
Number [Positive blood smears]	59	25	7	52	4

13. Secondary Outcome

Title	Prevalence of Parasitemia at the Time of Monthly Routine Visits During Pregnancy
Description	Detection of malaria parasites by LAMP during pregnancy
Time Frame	After first dose of study drug through delivery or early termination

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mothers - 3 Dose SP	Mothers - 3 Dose DP	Mothers - Monthly DP
Arm/Group Description	Sulfadoxine-Pyrimethamine 500mg/25mg	Dihydrioartemisinin-Piperaquine 40mg/320mg	Dihydroartemisinin-Piperaquine 20mg/160mg
Measure Participants	106	94	100
Measure Specimens	509	445	496
Number [Positive specimens]	206	74	26

14. Secondary Outcome

Title	Prevalence of Gametocytemia in Infants
Description	Proportion of routine blood smears positive for gametocytes
Time Frame	Birth up to 24 months of age or early study termination

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	3 Dose SP Pregnancy / 3 Monthly DP Infancy	3 Dose DP Pregnancy / 3 Monthly DP Infancy	3 Dose DP Pregnancy / Monthly DP Infancy	Monthly DP Pregnancy / 3 Monthly DP Infancy	Monthly DP Pregnancy / Monthly DP Infancy
Arm/Group Description	Women will be given SP (3 full strength tabs, 500 mg/25 mg) 3 times during pregnancy at 20, 28, and 36 weeks gestational age. In addition, placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two pills on day 1 (SP and placebo, DP and placebo, or two placebos) followed by one pill on days 2 and 3 (DP or placebo). Two placebos will be used, one that mimics the appearance of SP and one that mimics the appearance of DP. Infants will be given DP (once a day for 3 consecutive days using weight-based guidelines) every 12 weeks between 8 and 104 weeks of age. Infants randomized to receive DP every 12 weeks will receive placebo mimicking the dosing of DP every 4 weeks when they are not receiving study drug. 3 dose sulfadoxine-pyrimethamine (SP) for adult women during pregnancy 3-monthly dihydroartemisinin-piperaquine (DP) for infants	Women will be given DP (3 full strength tabs, 40 mg/320 mg, given once a day for 3 consecutive days) 3 times during pregnancy at 20, 28, and 36 weeks gestational age. In addition, placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two pills on day 1 (SP and placebo, DP and placebo, or two placebos) followed by one pill on days 2 and 3 (DP or placebo). Two placebos will be used, one that mimics the appearance of SP and one that mimics the appearance of DP. Infants will be given DP (once a day for 3 consecutive days using weight-based guidelines) every 12 weeks between 8 and 104 weeks of age. Infants randomized to receive DP every 12 weeks will receive placebo mimicking the dosing of DP every 4 weeks when they are not receiving study drug. 3 dose dihydroartemisinin-piperaquine (DP) for adult women during pregnancy 3-monthly dihydroartemisinin-piperaquine (DP) for infants	Women will be given DP (3 full strength tabs, 40 mg/320 mg, given once a day for 3 consecutive days) 3 times during pregnancy at 20, 28, and 36 weeks gestational age. In addition, placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two pills on day 1 (SP and placebo, DP and placebo, or two placebos) followed by one pill on days 2 and 3 (DP or placebo). Two placebos will be used, one that mimics the appearance of SP and one that mimics the appearance of DP. Infants will be given DP (once a day for 3 consecutive days using weight-based guidelines) every 4 weeks between 8 and 104 weeks of age. 3 dose dihydroartemisinin-piperaquine (DP) for adult women during pregnancy Monthly dihydroartemisinin-piperaquine (DP) for infants	Women will be given DP (3 full strength tabs, 40 mg/320 mg, given once a day for 3 consecutive days) every 4 weeks during pregnancy. In addition, placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two pills on day 1 (SP and placebo, DP and placebo, or two placebos) followed by one pill on days 2 and 3 (DP or placebo). Two placebos will be used, one that mimics the appearance of SP and one that mimics the appearance of DP. Infants will be given DP (once a day for 3 consecutive days) every 12 weeks between 8 and 104 weeks of age. Infants randomized to receive DP every 12 weeks will receive placebo mimicking the dosing of DP every 4 weeks when they are not receiving study drug. Monthly dihydroartemisinin-piperaquine (DP) for adult women during pregnancy 3-monthly dihydroartemisinin-piperaquine (DP) for infants	Women will be given DP (3 full strength tabs, 40 mg/320 mg, given once a day for 3 consecutive days) every 4 weeks during pregnancy. In addition, placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two pills on day 1 (SP and placebo, DP and placebo, or two placebos) followed by one pill on days 2 and 3 (DP or placebo). Two placebos will be used, one that mimics the appearance of SP and one that mimics the appearance of DP. Infants will be given DP (once a day for 3 consecutive days) every 4 weeks between 8 and 104 weeks of age. Monthly dihydroartemisinin-piperaquine (DP) for adult women during pregnancy Monthly dihydroartemisinin-piperaquine (DP) for infants
Measure Participants	101	44	49	48	52
Measure Blood smears	2393	1087	1156	1102	1218
Number [Positive blood smears]	7	1	0	4	0

Adverse Events

Time Frame	For women, from study drug initiation to 6 weeks postpartum or last observed date in study. For children, from study drug initiation to 4 weeks after last dose of study drugs.
Adverse Event Reporting Description	National Institutes of Health, Division of AIDS (DAIDS) Table for Grading the Severity of ADULT AND PEDIATRIC Adverse Events Version 1.0, December, 2004; clarification AUGUST 2009
Arm/Group Title	Mothers - 3 Dose SP		Mothers - 3 Dose DP		Mothers - Monthly DP		Infants - Monthly DP		Infants - 3 Monthly DP
Arm/Group Description	Women were given SP (3 full strength tabs, 500 mg/25 mg) 3 times during pregnancy at 20, 28, and 36 weeks gestational age. In addition, DP placebo was used to mimic the identical dosing strategy such that every 4 weeks women will receive two pills on day 1 (SP and DP placebo) followed by one pill on days 2 and 3 (DP placebo).		Women were given DP (3 full strength tabs, 40 mg/320 mg, given once a day for 3 consecutive days) 3 times during pregnancy at 20, 28, and 36 weeks gestational age. In addition, SP and DP placebos were used to mimic the identical dosing strategy as other arms such that every 4 weeks women will receive two pills on day 1 (DP and SP placebo) followed by one pill on days 2 and 3 (DP placebo).		Women were given DP (3 full strength tabs, 40 mg/320 mg, given once a day for 3 consecutive days) monthly. In addition, SP placebo to mimic the identical dosing strategy as other arms such that every 4 weeks women will receive two pills on day 1 (DP and SP placebo) followed by one pill on days 2 and 3 (DP).		DP half-strength tablets given once a day for 3 consecutive days according to weight based guidelines.		DP half-strength tablets given once a day for 3 consecutive days according to weight based guidelines. Infants received placebo mimicking the dosing of DP every 4 weeks when they are not receiving study drug.
All Cause Mortality
	Mothers - 3 Dose SP		Mothers - 3 Dose DP		Mothers - Monthly DP		Infants - Monthly DP		Infants - 3 Monthly DP
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/106 (0%)		0/94 (0%)		0/100 (0%)		4/100 (4%)		3/191 (1.6%)
Serious Adverse Events
	Mothers - 3 Dose SP		Mothers - 3 Dose DP		Mothers - Monthly DP		Infants - Monthly DP		Infants - 3 Monthly DP
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/106 (5.7%)		9/94 (9.6%)		3/100 (3%)		9/100 (9%)		15/191 (7.9%)
Blood and lymphatic system disorders
Anemia	2/106 (1.9%)	2	1/94 (1.1%)	1	2/100 (2%)	2	3/100 (3%)	3	1/191 (0.5%)	1
Preeclampsia	0/106 (0%)	0	0/94 (0%)	0	1/100 (1%)	1	0/100 (0%)	0	0/191 (0%)	0
Congenital, familial and genetic disorders
Congenital Anomaly	2/106 (1.9%)	2	4/94 (4.3%)	4	0/100 (0%)	0	0/100 (0%)	0	0/191 (0%)	0
Gastrointestinal disorders
Intestinal Obstruction	0/106 (0%)	0	0/94 (0%)	0	0/100 (0%)	0	0/100 (0%)	0	2/191 (1%)	2
Diarrhea	0/106 (0%)	0	0/94 (0%)	0	0/100 (0%)	0	1/100 (1%)	1	2/191 (1%)	2
General disorders
Elevated temperature	0/106 (0%)	0	0/94 (0%)	0	0/100 (0%)	0	1/100 (1%)	1	2/191 (1%)	2
Malnutrition	0/106 (0%)	0	0/94 (0%)	0	0/100 (0%)	0	1/100 (1%)	1	0/191 (0%)	0
Dehydration	0/106 (0%)	0	0/94 (0%)	0	0/100 (0%)	0	0/100 (0%)	0	1/191 (0.5%)	1
Immune system disorders
Neutropenia	0/106 (0%)	0	0/94 (0%)	0	0/100 (0%)	0	1/100 (1%)	1	0/191 (0%)	0
Nervous system disorders
Seizure	0/106 (0%)	0	0/94 (0%)	0	0/100 (0%)	0	1/100 (1%)	1	1/191 (0.5%)	1
Pregnancy, puerperium and perinatal conditions
Stillbirth	1/106 (0.9%)	1	1/94 (1.1%)	1	1/100 (1%)	1	0/100 (0%)	0	0/191 (0%)	0
Threatened Abortion	1/106 (0.9%)	1	0/94 (0%)	0	0/100 (0%)	0	0/100 (0%)	0	0/191 (0%)	0
Retained products of conception	0/106 (0%)	0	1/94 (1.1%)	1	0/100 (0%)	0	0/100 (0%)	0	0/191 (0%)	0
Psychiatric disorders
Altered Mental State	0/106 (0%)	0	0/94 (0%)	0	0/100 (0%)	0	0/100 (0%)	0	1/191 (0.5%)	1
Renal and urinary disorders
Pyelonephritis	0/106 (0%)	0	1/94 (1.1%)	1	0/100 (0%)	0	0/100 (0%)	0	0/191 (0%)	0
Elevated Alanine Aminotransferase	0/106 (0%)	0	0/94 (0%)	0	0/100 (0%)	0	1/100 (1%)	1	1/191 (0.5%)	1
Respiratory, thoracic and mediastinal disorders
Respiratory distress	0/106 (0%)	0	1/94 (1.1%)	1	0/100 (0%)	0	1/100 (1%)	1	3/191 (1.6%)	3
Cough	0/106 (0%)	0	0/94 (0%)	0	0/100 (0%)	0	2/100 (2%)	2	0/191 (0%)	0
Skin and subcutaneous tissue disorders
Burns	0/106 (0%)	0	0/94 (0%)	0	0/100 (0%)	0	0/100 (0%)	0	1/191 (0.5%)	1
Other (Not Including Serious) Adverse Events
	Mothers - 3 Dose SP		Mothers - 3 Dose DP		Mothers - Monthly DP		Infants - Monthly DP		Infants - 3 Monthly DP
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	90/106 (84.9%)		78/94 (83%)		89/100 (89%)		94/100 (94%)		183/191 (95.8%)
Blood and lymphatic system disorders
Anemia	9/106 (8.5%)	10	2/94 (2.1%)	3	4/100 (4%)	4	0/100 (0%)	0	0/191 (0%)	0
Thrombocytopenia	1/106 (0.9%)	1	0/94 (0%)	0	0/100 (0%)	0	0/100 (0%)	0	0/191 (0%)	0
Hypotension	0/106 (0%)	0	0/94 (0%)	0	1/100 (1%)	1	0/100 (0%)	0	0/191 (0%)	0
Eye disorders
Conjunctivitis	0/106 (0%)	0	0/94 (0%)	0	0/100 (0%)	0	27/100 (27%)	34	49/191 (25.7%)	62
Gastrointestinal disorders
Diarrhea	10/106 (9.4%)	12	8/94 (8.5%)	10	10/100 (10%)	13	87/100 (87%)	470	168/191 (88%)	938
Vomiting	7/106 (6.6%)	8	8/94 (8.5%)	8	8/100 (8%)	8	58/100 (58%)	114	117/191 (61.3%)	191
Nausea	2/106 (1.9%)	2	4/94 (4.3%)	4	2/100 (2%)	2	0/100 (0%)	0	0/191 (0%)	0
General disorders
Abdominal pain	74/106 (69.8%)	172	58/94 (61.7%)	122	73/100 (73%)	132	0/100 (0%)	0	0/191 (0%)	0
Cough	55/106 (51.9%)	94	48/94 (51.1%)	71	57/100 (57%)	77	94/100 (94%)	1127	183/191 (95.8%)	2230
Headache	56/106 (52.8%)	90	45/94 (47.9%)	70	55/100 (55%)	78	0/100 (0%)	0	0/191 (0%)	0
Chills	20/106 (18.9%)	21	13/94 (13.8%)	14	11/100 (11%)	12	0/100 (0%)	0	0/191 (0%)	0
Malaise	15/106 (14.2%)	16	9/94 (9.6%)	9	6/100 (6%)	8	10/100 (10%)	10	25/191 (13.1%)	28
Dysphagia	9/106 (8.5%)	9	2/94 (2.1%)	2	13/100 (13%)	14	0/100 (0%)	0	0/191 (0%)	0
Anorexia	2/106 (1.9%)	2	0/94 (0%)	0	4/100 (4%)	4	16/100 (16%)	18	43/191 (22.5%)	191
Renal and urinary disorders
Urinary tract infection	3/106 (2.8%)	3	2/94 (2.1%)	2	2/100 (2%)	2	0/100 (0%)	0	0/191 (0%)	0
Skin and subcutaneous tissue disorders
Rash	0/106 (0%)	0	0/94 (0%)	0	0/100 (0%)	0	29/100 (29%)	43	56/191 (29.3%)	191

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.