Trial Outcomes & Findings for Prevention of Malaria in HIV-uninfected Pregnant Women and Infants (NCT NCT02793622)
NCT ID: NCT02793622
Last Updated: 2021-04-14
Results Overview
Composite adverse birth outcome defined as any one of the following: 1) Low birth weight (\< 2500 gm); 2) Preterm delivery (\< 37 weeks gestational age); 3) Small for gestational age (\< 10th percentile relative to an external growth reference)
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
782 participants
Primary outcome timeframe
Delivery
Results posted on
2021-04-14
Participant Flow
Participant milestones
| Measure |
Monthly Sulfadoxine-Pyrimethamine (SP) During Pregnancy
Women will be given SP (3 full strength tabs, 500 mg/25 mg) every four weeks times during pregnancy. In addition, placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two drugs on day 1 (SP and placebo or DP and placebo) followed by one drug 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.
Monthly Sulfadoxine-Pyrimethamine (SP) During Pregnancy
|
Monthly Dihydroartemisinin-Piperaquine (DP) During Pregnancy
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 drugs on day 1 (SP and placebo or DP and placebo) followed by one drug 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.
Monthly Dihydroartemisinin-Piperaquine (DP) During Pregnancy
|
|---|---|---|
|
Overall Study
STARTED
|
391
|
391
|
|
Overall Study
COMPLETED
|
338
|
349
|
|
Overall Study
NOT COMPLETED
|
53
|
42
|
Reasons for withdrawal
| Measure |
Monthly Sulfadoxine-Pyrimethamine (SP) During Pregnancy
Women will be given SP (3 full strength tabs, 500 mg/25 mg) every four weeks times during pregnancy. In addition, placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two drugs on day 1 (SP and placebo or DP and placebo) followed by one drug 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.
Monthly Sulfadoxine-Pyrimethamine (SP) During Pregnancy
|
Monthly Dihydroartemisinin-Piperaquine (DP) During Pregnancy
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 drugs on day 1 (SP and placebo or DP and placebo) followed by one drug 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.
Monthly Dihydroartemisinin-Piperaquine (DP) During Pregnancy
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
31
|
19
|
|
Overall Study
Withdrawal by Subject
|
21
|
17
|
|
Overall Study
Adverse Event
|
0
|
1
|
|
Overall Study
Protocol Violation
|
1
|
5
|
Baseline Characteristics
Prevention of Malaria in HIV-uninfected Pregnant Women and Infants
Baseline characteristics by cohort
| Measure |
Monthly Sulfadoxine-Pyrimethamine (SP) During Pregnancy
n=391 Participants
Women will be given SP (3 full strength tabs, 500 mg/25 mg) every four weeks times during pregnancy. In addition, placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two drugs on day 1 (SP and placebo or DP and placebo) followed by one drug 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.
Monthly Sulfadoxine-Pyrimethamine (SP) During Pregnancy
|
Monthly Dihydroartemisinin-Piperaquine (DP) During Pregnancy
n=391 Participants
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 drugs on day 1 (SP and placebo or DP and placebo) followed by one drug 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.
Monthly Dihydroartemisinin-Piperaquine (DP) During Pregnancy
|
Total
n=782 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
23 years
n=5 Participants
|
23 years
n=7 Participants
|
23 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
391 Participants
n=5 Participants
|
391 Participants
n=7 Participants
|
782 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
391 Participants
n=5 Participants
|
391 Participants
n=7 Participants
|
782 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
Uganda
|
391 participants
n=5 Participants
|
391 participants
n=7 Participants
|
782 participants
n=5 Participants
|
|
Gestational age category (weeks)
12-16 weeks
|
234 Participants
n=5 Participants
|
242 Participants
n=7 Participants
|
476 Participants
n=5 Participants
|
|
Gestational age category (weeks)
>16-20 weeks
|
157 Participants
n=5 Participants
|
149 Participants
n=7 Participants
|
306 Participants
n=5 Participants
|
|
Detection of malaria parasites by microscopy or qPCR
|
326 Participants
n=5 Participants
|
317 Participants
n=7 Participants
|
643 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: DeliveryPopulation: Number of livebirths reported here. SP: 338 women followed through delivery resulting in 348 infants (10 twin sets). 9 mothers/infants excluded (4 spontaneous abortions, 5 stillbirths). DP: 349 women followed through delivery resulting in 352 infants (3 twin sets). 12 mothers and 13 infants excluded (10 spontaneous abortions, 3 stillbirths).
Composite adverse birth outcome defined as any one of the following: 1) Low birth weight (\< 2500 gm); 2) Preterm delivery (\< 37 weeks gestational age); 3) Small for gestational age (\< 10th percentile relative to an external growth reference)
Outcome measures
| Measure |
Monthly Sulfadoxine-Pyrimethamine (SP) During Pregnancy
n=329 Participants
Women will be given SP (3 full strength tabs, 500 mg/25 mg) every four weeks times during pregnancy. In addition, placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two drugs on day 1 (SP and placebo or DP and placebo) followed by one drug 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.
Monthly Sulfadoxine-Pyrimethamine (SP) During Pregnancy
|
Monthly Dihydroartemisinin-Piperaquine (DP) During Pregnancy
n=337 Participants
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 drugs on day 1 (SP and placebo or DP and placebo) followed by one drug 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.
Monthly Dihydroartemisinin-Piperaquine (DP) During Pregnancy
|
|---|---|---|
|
Number of Participants Who Deliver With a Composite Adverse Birth Outcome
|
60 Participants
|
54 Participants
|
PRIMARY outcome
Timeframe: Time at risk will begin at birth and end when study participants reaches 12 months of age or early study terminationPopulation: 339 live births included in the analyses for both groups.
episodes per person year
Outcome measures
| Measure |
Monthly Sulfadoxine-Pyrimethamine (SP) During Pregnancy
n=339 Participants
Women will be given SP (3 full strength tabs, 500 mg/25 mg) every four weeks times during pregnancy. In addition, placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two drugs on day 1 (SP and placebo or DP and placebo) followed by one drug 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.
Monthly Sulfadoxine-Pyrimethamine (SP) During Pregnancy
|
Monthly Dihydroartemisinin-Piperaquine (DP) During Pregnancy
n=339 Participants
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 drugs on day 1 (SP and placebo or DP and placebo) followed by one drug 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.
Monthly Dihydroartemisinin-Piperaquine (DP) During Pregnancy
|
|---|---|---|
|
Incidence of Malaria in Infants
|
1.98 episodes per person year
|
1.71 episodes per person year
|
PRIMARY outcome
Timeframe: At the time of deliveryPopulation: 339 live births included in the analyses for both groups.
Gestational age in weeks determined by ultrasound dating (gold standard) and by the metabolic profiling outcome from biological specimens including placental tissue and placental blood.
Outcome measures
| Measure |
Monthly Sulfadoxine-Pyrimethamine (SP) During Pregnancy
n=339 Participants
Women will be given SP (3 full strength tabs, 500 mg/25 mg) every four weeks times during pregnancy. In addition, placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two drugs on day 1 (SP and placebo or DP and placebo) followed by one drug 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.
Monthly Sulfadoxine-Pyrimethamine (SP) During Pregnancy
|
Monthly Dihydroartemisinin-Piperaquine (DP) During Pregnancy
n=339 Participants
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 drugs on day 1 (SP and placebo or DP and placebo) followed by one drug 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.
Monthly Dihydroartemisinin-Piperaquine (DP) During Pregnancy
|
|---|---|---|
|
Mean Gestational Age in Weeks at Birth
|
39.4 weeks
Standard Deviation 1.9
|
39.6 weeks
Standard Deviation 1.6
|
SECONDARY outcome
Timeframe: DeliveryPopulation: analysis population is women who delivered and had histopathology results (i.e. some women who delivered did not have histopathology results)
Any evidence of placental infection (parasites or pigment). Number of participants with placental tissue positive for malaria parasites or pigment.
Outcome measures
| Measure |
Monthly Sulfadoxine-Pyrimethamine (SP) During Pregnancy
n=322 Participants
Women will be given SP (3 full strength tabs, 500 mg/25 mg) every four weeks times during pregnancy. In addition, placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two drugs on day 1 (SP and placebo or DP and placebo) followed by one drug 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.
Monthly Sulfadoxine-Pyrimethamine (SP) During Pregnancy
|
Monthly Dihydroartemisinin-Piperaquine (DP) During Pregnancy
n=331 Participants
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 drugs on day 1 (SP and placebo or DP and placebo) followed by one drug 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.
Monthly Dihydroartemisinin-Piperaquine (DP) During Pregnancy
|
|---|---|---|
|
Prevalence of Placental Malaria by Histology
|
197 Participants
|
94 Participants
|
SECONDARY outcome
Timeframe: DeliveryPopulation: LAMP and microscopy performed for the number of participants reported in each group.
Proportion of placental blood samples positive for parasites by Loop-mediated isothermal amplification (LAMP) or microscopy
Outcome measures
| Measure |
Monthly Sulfadoxine-Pyrimethamine (SP) During Pregnancy
n=339 Participants
Women will be given SP (3 full strength tabs, 500 mg/25 mg) every four weeks times during pregnancy. In addition, placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two drugs on day 1 (SP and placebo or DP and placebo) followed by one drug 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.
Monthly Sulfadoxine-Pyrimethamine (SP) During Pregnancy
|
Monthly Dihydroartemisinin-Piperaquine (DP) During Pregnancy
n=339 Participants
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 drugs on day 1 (SP and placebo or DP and placebo) followed by one drug 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.
Monthly Dihydroartemisinin-Piperaquine (DP) During Pregnancy
|
|---|---|---|
|
Prevalence of Placental Parasitemia
LAMP
|
71 Participants
|
7 Participants
|
|
Prevalence of Placental Parasitemia
Microscopy
|
29 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Gestational age between 12-20 weeks (at study entry) up to deliveryMaternal blood positive for malaria parasites by microscopy.
Outcome measures
| Measure |
Monthly Sulfadoxine-Pyrimethamine (SP) During Pregnancy
n=336 Participants
Women will be given SP (3 full strength tabs, 500 mg/25 mg) every four weeks times during pregnancy. In addition, placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two drugs on day 1 (SP and placebo or DP and placebo) followed by one drug 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.
Monthly Sulfadoxine-Pyrimethamine (SP) During Pregnancy
|
Monthly Dihydroartemisinin-Piperaquine (DP) During Pregnancy
n=342 Participants
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 drugs on day 1 (SP and placebo or DP and placebo) followed by one drug 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.
Monthly Dihydroartemisinin-Piperaquine (DP) During Pregnancy
|
|---|---|---|
|
Prevalence of Maternal Malaria
|
28 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Starting at the time of their first study drug administration, approximately gestational age between 12-20 weeks, up to one month post-deliveryAll grade 3 and 4 adverse events
Outcome measures
| Measure |
Monthly Sulfadoxine-Pyrimethamine (SP) During Pregnancy
n=375 Participants
Women will be given SP (3 full strength tabs, 500 mg/25 mg) every four weeks times during pregnancy. In addition, placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two drugs on day 1 (SP and placebo or DP and placebo) followed by one drug 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.
Monthly Sulfadoxine-Pyrimethamine (SP) During Pregnancy
|
Monthly Dihydroartemisinin-Piperaquine (DP) During Pregnancy
n=373 Participants
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 drugs on day 1 (SP and placebo or DP and placebo) followed by one drug 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.
Monthly Dihydroartemisinin-Piperaquine (DP) During Pregnancy
|
|---|---|---|
|
Number of Participants With Adverse Events
|
54 Participants
|
43 Participants
|
SECONDARY outcome
Timeframe: Starting at the time of their first study drug administration, approximately gestational age between 12-20 weeks, up to one month post-deliveryPopulation: Number of women initiated on study drugs reported here.
hemoglobin \< 11 g/dL
Outcome measures
| Measure |
Monthly Sulfadoxine-Pyrimethamine (SP) During Pregnancy
n=375 Participants
Women will be given SP (3 full strength tabs, 500 mg/25 mg) every four weeks times during pregnancy. In addition, placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two drugs on day 1 (SP and placebo or DP and placebo) followed by one drug 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.
Monthly Sulfadoxine-Pyrimethamine (SP) During Pregnancy
|
Monthly Dihydroartemisinin-Piperaquine (DP) During Pregnancy
n=373 Participants
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 drugs on day 1 (SP and placebo or DP and placebo) followed by one drug 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.
Monthly Dihydroartemisinin-Piperaquine (DP) During Pregnancy
|
|---|---|---|
|
Prevalence of Anemia in Pregnant Women
|
28 Participants
|
8 Participants
|
SECONDARY outcome
Timeframe: Birth up to 12 months of age or early terminationPopulation: 339 live births included in the analyses for both groups.
Defined as the proportion with hemoglobin \< 10 g/dL measure routinely at 12, 28, and 52 weeks of age. Number of cases per person year (PPY). This is a prevalence measure but are repeated measures during infancy. In other words we measured this outcome up to 3 times for each participant during infancy (at 12, 28 and 52 weeks of age).
Outcome measures
| Measure |
Monthly Sulfadoxine-Pyrimethamine (SP) During Pregnancy
n=878 routine hemoglobin measurement
Women will be given SP (3 full strength tabs, 500 mg/25 mg) every four weeks times during pregnancy. In addition, placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two drugs on day 1 (SP and placebo or DP and placebo) followed by one drug 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.
Monthly Sulfadoxine-Pyrimethamine (SP) During Pregnancy
|
Monthly Dihydroartemisinin-Piperaquine (DP) During Pregnancy
n=892 routine hemoglobin measurement
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 drugs on day 1 (SP and placebo or DP and placebo) followed by one drug 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.
Monthly Dihydroartemisinin-Piperaquine (DP) During Pregnancy
|
|---|---|---|
|
Prevalence of Anemia in Infants
|
222 routine hemoglobin measurement
|
216 routine hemoglobin measurement
|
SECONDARY outcome
Timeframe: Starting at the time of their first study drug administration, approximately gestational age between 12-20 weeks, up to one month post-deliveryProportion of routine monthly samples positive for parasites by microscopy and LAMP
Outcome measures
| Measure |
Monthly Sulfadoxine-Pyrimethamine (SP) During Pregnancy
n=1687 blood smears
Women will be given SP (3 full strength tabs, 500 mg/25 mg) every four weeks times during pregnancy. In addition, placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two drugs on day 1 (SP and placebo or DP and placebo) followed by one drug 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.
Monthly Sulfadoxine-Pyrimethamine (SP) During Pregnancy
|
Monthly Dihydroartemisinin-Piperaquine (DP) During Pregnancy
n=1757 blood smears
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 drugs on day 1 (SP and placebo or DP and placebo) followed by one drug 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.
Monthly Dihydroartemisinin-Piperaquine (DP) During Pregnancy
|
|---|---|---|
|
Prevalence of Asymptomatic Parasitemia in Pregnant Women
|
519 blood smears
|
9 blood smears
|
SECONDARY outcome
Timeframe: Birth up to 12 months of age or early terminationProportion of routine monthly samples positive for parasites by microscopy and LAMP
Outcome measures
| Measure |
Monthly Sulfadoxine-Pyrimethamine (SP) During Pregnancy
n=3879 blood smears
Women will be given SP (3 full strength tabs, 500 mg/25 mg) every four weeks times during pregnancy. In addition, placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two drugs on day 1 (SP and placebo or DP and placebo) followed by one drug 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.
Monthly Sulfadoxine-Pyrimethamine (SP) During Pregnancy
|
Monthly Dihydroartemisinin-Piperaquine (DP) During Pregnancy
n=3933 blood smears
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 drugs on day 1 (SP and placebo or DP and placebo) followed by one drug 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.
Monthly Dihydroartemisinin-Piperaquine (DP) During Pregnancy
|
|---|---|---|
|
Prevalence of Asymptomatic Parasitemia in Infants
|
344 blood smears
|
357 blood smears
|
SECONDARY outcome
Timeframe: Birth up to 12 months of age or early terminationPopulation: 339 live births included in the analyses for both groups.
Complicated malaria defined as an episode of malaria with danger signs (any of the following: less than 3 convulsions over 24 h, inability to sit or stand, vomiting everything, unable to breastfeed or drink) or the meeting standardized criteria for severe malaria.
Outcome measures
| Measure |
Monthly Sulfadoxine-Pyrimethamine (SP) During Pregnancy
n=339 Participants
Women will be given SP (3 full strength tabs, 500 mg/25 mg) every four weeks times during pregnancy. In addition, placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two drugs on day 1 (SP and placebo or DP and placebo) followed by one drug 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.
Monthly Sulfadoxine-Pyrimethamine (SP) During Pregnancy
|
Monthly Dihydroartemisinin-Piperaquine (DP) During Pregnancy
n=339 Participants
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 drugs on day 1 (SP and placebo or DP and placebo) followed by one drug 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.
Monthly Dihydroartemisinin-Piperaquine (DP) During Pregnancy
|
|---|---|---|
|
Incidence of Complicated Malaria in Infants
|
44 Participants
|
24 Participants
|
SECONDARY outcome
Timeframe: Birth up to 12 months of age or early terminationPopulation: 339 live births included in the analyses for both groups.
Admission to the pediatric ward for any cause
Outcome measures
| Measure |
Monthly Sulfadoxine-Pyrimethamine (SP) During Pregnancy
n=339 Participants
Women will be given SP (3 full strength tabs, 500 mg/25 mg) every four weeks times during pregnancy. In addition, placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two drugs on day 1 (SP and placebo or DP and placebo) followed by one drug 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.
Monthly Sulfadoxine-Pyrimethamine (SP) During Pregnancy
|
Monthly Dihydroartemisinin-Piperaquine (DP) During Pregnancy
n=339 Participants
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 drugs on day 1 (SP and placebo or DP and placebo) followed by one drug 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.
Monthly Dihydroartemisinin-Piperaquine (DP) During Pregnancy
|
|---|---|---|
|
Incidence of Hospital Admissions in Infants
|
19 Participants
|
8 Participants
|
SECONDARY outcome
Timeframe: Birth up to 12 months of agePopulation: 339 live births included in the analyses for both groups.
Any deaths occurring after birth
Outcome measures
| Measure |
Monthly Sulfadoxine-Pyrimethamine (SP) During Pregnancy
n=339 Participants
Women will be given SP (3 full strength tabs, 500 mg/25 mg) every four weeks times during pregnancy. In addition, placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two drugs on day 1 (SP and placebo or DP and placebo) followed by one drug 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.
Monthly Sulfadoxine-Pyrimethamine (SP) During Pregnancy
|
Monthly Dihydroartemisinin-Piperaquine (DP) During Pregnancy
n=339 Participants
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 drugs on day 1 (SP and placebo or DP and placebo) followed by one drug 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.
Monthly Dihydroartemisinin-Piperaquine (DP) During Pregnancy
|
|---|---|---|
|
Infant Mortality Rate
|
9 Participants
|
7 Participants
|
Adverse Events
Monthly Sulfadoxine-Pyrimethamine (SP) During Pregnancy
Serious events: 11 serious events
Other events: 341 other events
Deaths: 1 deaths
Monthly Dihydroartemisinin-Piperaquine (DP) During Pregnancy
Serious events: 19 serious events
Other events: 341 other events
Deaths: 3 deaths
Serious adverse events
| Measure |
Monthly Sulfadoxine-Pyrimethamine (SP) During Pregnancy
n=375 participants at risk
Women will be given SP (3 full strength tabs, 500 mg/25 mg) every four weeks times during pregnancy. In addition, placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two drugs on day 1 (SP and placebo or DP and placebo) followed by one drug 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.
Monthly Sulfadoxine-Pyrimethamine (SP) During Pregnancy
|
Monthly Dihydroartemisinin-Piperaquine (DP) During Pregnancy
n=373 participants at risk
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 drugs on day 1 (SP and placebo or DP and placebo) followed by one drug 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.
Monthly Dihydroartemisinin-Piperaquine (DP) During Pregnancy
|
|---|---|---|
|
Blood and lymphatic system disorders
Anemia
|
1.1%
4/375 • Number of events 4 • Adverse event data were collected following the initiation of study drugs through to 6 weeks postpartum.
Adverse events were assessed and graded according to standardized criteria (National Institutes of Health, Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0) at every visit to the study clinic. The number of participants at risk are all women that were enrolled, randomized, AND received at least 1 dose of study drugs.
|
0.54%
2/373 • Number of events 2 • Adverse event data were collected following the initiation of study drugs through to 6 weeks postpartum.
Adverse events were assessed and graded according to standardized criteria (National Institutes of Health, Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0) at every visit to the study clinic. The number of participants at risk are all women that were enrolled, randomized, AND received at least 1 dose of study drugs.
|
|
Congenital, familial and genetic disorders
Congenital anomaly
|
0.53%
2/375 • Number of events 2 • Adverse event data were collected following the initiation of study drugs through to 6 weeks postpartum.
Adverse events were assessed and graded according to standardized criteria (National Institutes of Health, Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0) at every visit to the study clinic. The number of participants at risk are all women that were enrolled, randomized, AND received at least 1 dose of study drugs.
|
2.7%
10/373 • Number of events 10 • Adverse event data were collected following the initiation of study drugs through to 6 weeks postpartum.
Adverse events were assessed and graded according to standardized criteria (National Institutes of Health, Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0) at every visit to the study clinic. The number of participants at risk are all women that were enrolled, randomized, AND received at least 1 dose of study drugs.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
1.3%
5/375 • Number of events 5 • Adverse event data were collected following the initiation of study drugs through to 6 weeks postpartum.
Adverse events were assessed and graded according to standardized criteria (National Institutes of Health, Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0) at every visit to the study clinic. The number of participants at risk are all women that were enrolled, randomized, AND received at least 1 dose of study drugs.
|
0.54%
2/373 • Number of events 2 • Adverse event data were collected following the initiation of study drugs through to 6 weeks postpartum.
Adverse events were assessed and graded according to standardized criteria (National Institutes of Health, Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0) at every visit to the study clinic. The number of participants at risk are all women that were enrolled, randomized, AND received at least 1 dose of study drugs.
|
|
Blood and lymphatic system disorders
Elevated Alanine Aminotransferase
|
0.00%
0/375 • Adverse event data were collected following the initiation of study drugs through to 6 weeks postpartum.
Adverse events were assessed and graded according to standardized criteria (National Institutes of Health, Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0) at every visit to the study clinic. The number of participants at risk are all women that were enrolled, randomized, AND received at least 1 dose of study drugs.
|
0.27%
1/373 • Number of events 1 • Adverse event data were collected following the initiation of study drugs through to 6 weeks postpartum.
Adverse events were assessed and graded according to standardized criteria (National Institutes of Health, Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0) at every visit to the study clinic. The number of participants at risk are all women that were enrolled, randomized, AND received at least 1 dose of study drugs.
|
|
Psychiatric disorders
Altered mental status
|
0.00%
0/375 • Adverse event data were collected following the initiation of study drugs through to 6 weeks postpartum.
Adverse events were assessed and graded according to standardized criteria (National Institutes of Health, Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0) at every visit to the study clinic. The number of participants at risk are all women that were enrolled, randomized, AND received at least 1 dose of study drugs.
|
0.27%
1/373 • Number of events 1 • Adverse event data were collected following the initiation of study drugs through to 6 weeks postpartum.
Adverse events were assessed and graded according to standardized criteria (National Institutes of Health, Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0) at every visit to the study clinic. The number of participants at risk are all women that were enrolled, randomized, AND received at least 1 dose of study drugs.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia
|
0.27%
1/375 • Number of events 1 • Adverse event data were collected following the initiation of study drugs through to 6 weeks postpartum.
Adverse events were assessed and graded according to standardized criteria (National Institutes of Health, Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0) at every visit to the study clinic. The number of participants at risk are all women that were enrolled, randomized, AND received at least 1 dose of study drugs.
|
0.27%
1/373 • Number of events 1 • Adverse event data were collected following the initiation of study drugs through to 6 weeks postpartum.
Adverse events were assessed and graded according to standardized criteria (National Institutes of Health, Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0) at every visit to the study clinic. The number of participants at risk are all women that were enrolled, randomized, AND received at least 1 dose of study drugs.
|
|
Pregnancy, puerperium and perinatal conditions
Haemorrhage
|
0.00%
0/375 • Adverse event data were collected following the initiation of study drugs through to 6 weeks postpartum.
Adverse events were assessed and graded according to standardized criteria (National Institutes of Health, Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0) at every visit to the study clinic. The number of participants at risk are all women that were enrolled, randomized, AND received at least 1 dose of study drugs.
|
0.54%
2/373 • Number of events 2 • Adverse event data were collected following the initiation of study drugs through to 6 weeks postpartum.
Adverse events were assessed and graded according to standardized criteria (National Institutes of Health, Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0) at every visit to the study clinic. The number of participants at risk are all women that were enrolled, randomized, AND received at least 1 dose of study drugs.
|
Other adverse events
| Measure |
Monthly Sulfadoxine-Pyrimethamine (SP) During Pregnancy
n=375 participants at risk
Women will be given SP (3 full strength tabs, 500 mg/25 mg) every four weeks times during pregnancy. In addition, placebos will be used to mimic the identical dosing strategy such that every 4 weeks women will receive two drugs on day 1 (SP and placebo or DP and placebo) followed by one drug 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.
Monthly Sulfadoxine-Pyrimethamine (SP) During Pregnancy
|
Monthly Dihydroartemisinin-Piperaquine (DP) During Pregnancy
n=373 participants at risk
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 drugs on day 1 (SP and placebo or DP and placebo) followed by one drug 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.
Monthly Dihydroartemisinin-Piperaquine (DP) During Pregnancy
|
|---|---|---|
|
General disorders
Abdominal pain
|
72.8%
273/375 • Number of events 822 • Adverse event data were collected following the initiation of study drugs through to 6 weeks postpartum.
Adverse events were assessed and graded according to standardized criteria (National Institutes of Health, Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0) at every visit to the study clinic. The number of participants at risk are all women that were enrolled, randomized, AND received at least 1 dose of study drugs.
|
75.6%
282/373 • Number of events 800 • Adverse event data were collected following the initiation of study drugs through to 6 weeks postpartum.
Adverse events were assessed and graded according to standardized criteria (National Institutes of Health, Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0) at every visit to the study clinic. The number of participants at risk are all women that were enrolled, randomized, AND received at least 1 dose of study drugs.
|
|
General disorders
Cough
|
67.7%
254/375 • Number of events 603 • Adverse event data were collected following the initiation of study drugs through to 6 weeks postpartum.
Adverse events were assessed and graded according to standardized criteria (National Institutes of Health, Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0) at every visit to the study clinic. The number of participants at risk are all women that were enrolled, randomized, AND received at least 1 dose of study drugs.
|
71.8%
268/373 • Number of events 681 • Adverse event data were collected following the initiation of study drugs through to 6 weeks postpartum.
Adverse events were assessed and graded according to standardized criteria (National Institutes of Health, Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0) at every visit to the study clinic. The number of participants at risk are all women that were enrolled, randomized, AND received at least 1 dose of study drugs.
|
|
General disorders
Headache
|
68.3%
256/375 • Number of events 586 • Adverse event data were collected following the initiation of study drugs through to 6 weeks postpartum.
Adverse events were assessed and graded according to standardized criteria (National Institutes of Health, Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0) at every visit to the study clinic. The number of participants at risk are all women that were enrolled, randomized, AND received at least 1 dose of study drugs.
|
63.5%
237/373 • Number of events 604 • Adverse event data were collected following the initiation of study drugs through to 6 weeks postpartum.
Adverse events were assessed and graded according to standardized criteria (National Institutes of Health, Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0) at every visit to the study clinic. The number of participants at risk are all women that were enrolled, randomized, AND received at least 1 dose of study drugs.
|
|
Renal and urinary disorders
Pyuria
|
13.6%
51/375 • Number of events 63 • Adverse event data were collected following the initiation of study drugs through to 6 weeks postpartum.
Adverse events were assessed and graded according to standardized criteria (National Institutes of Health, Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0) at every visit to the study clinic. The number of participants at risk are all women that were enrolled, randomized, AND received at least 1 dose of study drugs.
|
15.8%
59/373 • Number of events 69 • Adverse event data were collected following the initiation of study drugs through to 6 weeks postpartum.
Adverse events were assessed and graded according to standardized criteria (National Institutes of Health, Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0) at every visit to the study clinic. The number of participants at risk are all women that were enrolled, randomized, AND received at least 1 dose of study drugs.
|
|
Gastrointestinal disorders
Diarrhea
|
13.3%
50/375 • Number of events 62 • Adverse event data were collected following the initiation of study drugs through to 6 weeks postpartum.
Adverse events were assessed and graded according to standardized criteria (National Institutes of Health, Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0) at every visit to the study clinic. The number of participants at risk are all women that were enrolled, randomized, AND received at least 1 dose of study drugs.
|
13.1%
49/373 • Number of events 66 • Adverse event data were collected following the initiation of study drugs through to 6 weeks postpartum.
Adverse events were assessed and graded according to standardized criteria (National Institutes of Health, Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0) at every visit to the study clinic. The number of participants at risk are all women that were enrolled, randomized, AND received at least 1 dose of study drugs.
|
|
General disorders
Malaise
|
12.8%
48/375 • Number of events 54 • Adverse event data were collected following the initiation of study drugs through to 6 weeks postpartum.
Adverse events were assessed and graded according to standardized criteria (National Institutes of Health, Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0) at every visit to the study clinic. The number of participants at risk are all women that were enrolled, randomized, AND received at least 1 dose of study drugs.
|
11.8%
44/373 • Number of events 52 • Adverse event data were collected following the initiation of study drugs through to 6 weeks postpartum.
Adverse events were assessed and graded according to standardized criteria (National Institutes of Health, Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0) at every visit to the study clinic. The number of participants at risk are all women that were enrolled, randomized, AND received at least 1 dose of study drugs.
|
|
Gastrointestinal disorders
Vomitting
|
9.1%
34/375 • Number of events 44 • Adverse event data were collected following the initiation of study drugs through to 6 weeks postpartum.
Adverse events were assessed and graded according to standardized criteria (National Institutes of Health, Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0) at every visit to the study clinic. The number of participants at risk are all women that were enrolled, randomized, AND received at least 1 dose of study drugs.
|
9.4%
35/373 • Number of events 45 • Adverse event data were collected following the initiation of study drugs through to 6 weeks postpartum.
Adverse events were assessed and graded according to standardized criteria (National Institutes of Health, Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0) at every visit to the study clinic. The number of participants at risk are all women that were enrolled, randomized, AND received at least 1 dose of study drugs.
|
|
General disorders
Chills
|
6.9%
26/375 • Number of events 27 • Adverse event data were collected following the initiation of study drugs through to 6 weeks postpartum.
Adverse events were assessed and graded according to standardized criteria (National Institutes of Health, Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0) at every visit to the study clinic. The number of participants at risk are all women that were enrolled, randomized, AND received at least 1 dose of study drugs.
|
6.4%
24/373 • Number of events 26 • Adverse event data were collected following the initiation of study drugs through to 6 weeks postpartum.
Adverse events were assessed and graded according to standardized criteria (National Institutes of Health, Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0) at every visit to the study clinic. The number of participants at risk are all women that were enrolled, randomized, AND received at least 1 dose of study drugs.
|
Additional Information
Grant Dorsey, MD
University of California, San Francisco
Phone: 628-206-4680
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place