Efficacy and Safety of IPTp-DP Versus IPTp-SP in Malawi

NCT03009526 | Completed Phase 3 DMC

• 1 other identifier: MAC-P.02/16/1872
• Study Type: interventional
• Target: 602
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to compare the efficacy of monthly IPTp-DP with monthly IPTp-SP to determine if IPTp-DP is associated with a reduction in malaria infection at delivery among HIV-negative women in an area with high levels of SP resistance in Malawi.

Conditions

Malaria; Pregnancy

Keywords

Malaria; Pregnancy; Malawi; Intermittent preventive treatment; dihydroartemisinin-piperaquine; sulfadoxine-pyrimethamine

Outcome Measures

Primary Outcomes (2)

• Malaria infection at the time of delivery

  The composite of peripheral and placental parasitemia, detected by placental histology, positive peripheral blood smear at the time of delivery, or positive rapid diagnostic test at the time of delivery

  delivery

• Fetal morbidity

  Composite endpoint of fetal morbidity, defined as any of the following: Preterm birth (birth before 37 weeks gestation), Low-birth-weight (birth weight under 2,500 grams), Small for gestational age (SGA)

  Delivery

Secondary Outcomes (8)

• Electrocardiogram changes following the receipt of DP

  4-6 hours after the 3rd dose with each course

• Microbiome changes following receipt of DP or SP

  From date of randomization until the date of delivery or last date of follow-up, average of ~4-5 months

• Maternal hemoglobin at 3rd trimester

  3rd trimester

• Maternal anemia at 3rd trimester

  3rd trimester

• Fetal anemia

  Delivery

Study Arms (2)

Sulfadoxine-pyrimethamine

ACTIVE COMPARATOR

Intermittent preventive treatment with Sulfadoxine-pyrimethamine: Monthly dose of 3 co-formulated tablets containing 500 mg sulfadoxine and 25 mg pyrimethamine

Drug: Sulfadoxine-pyrimethamine

dihydroartemisinin-piperaquine

EXPERIMENTAL

Intermittent preventive treatment with dihydroartemisinin-piperaquine: Monthly course of daily doses of co-formulated DP tablets containing 40 mg dihydroartemisinin and 320 mg piperaquine, dosed based on the woman's weight, for 3 days: * 24-35.9 kg: Two tablets * 36-59.9 kg: Three tablets * 60-79.9 kg: Four tablets * ≥80 kg: Five tablets

Drug: dihydroartemisinin-piperaquine

Interventions

Sulfadoxine-pyrimethamine DRUG

500 mg sulfadoxine and 25 mg pyrimethamine

Also known as: Fansidar

Sulfadoxine-pyrimethamine

dihydroartemisinin-piperaquine DRUG

40 mg dihydroartemisinin and 320 mg piperaquine

dihydroartemisinin-piperaquine

Eligibility Criteria

• Age: 16 Years+
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Viable singleton pregnancy
• Gestational age ≤28 completed weeks (28 6/7) by fundal height/ultrasound
• Maternal age ≥16 years
• No history of IPTp use during this pregnancy
• Willing to participate and complete the study schedule, including laboratory studies and delivery in the labor ward of the study clinic or hospital
• Willing to sign or thumb print informed consent
• Resident of study area and intending to stay in the area for the duration of the follow-up
• HIV-negative at enrolment

You may not qualify if:

• HIV-positive or unknown
• Multiple gestation
• High-risk pregnancy, including any pre-existing illness likely to cause complication of pregnancy (hypertension, diabetes, asthma, epilepsy, renal disease, liver disease, fistula repair, leg or spine deformity)
• Severe anemia requiring blood transfusion (Hb \<7.0 g/dL) at enrolment
• Known allergy or previous adverse reaction to any of the study drugs
• Participating in other malaria intervention studies
• Known or suspected cardiac disease
• Corrected QT interval (QTcF) greater than 450 ms at baseline
• Patients taking any of the following drugs:
• Antimicrobial agents of the following classes (systemic use only):
• Macrolides (e.g. erythromycin, clarithromycin, azithromycin, roxithromycin)
• Fluoroquinolones (e.g., levofloxacin, moxifloxacin, sparfloxacin)
• Pentamidine
• Antiarrhythmic agents (e.g. amiodarone, sotalol)
• Antihistamines (e.g. promethazine)

Sponsors & Collaborators

• Kamuzu University of Health Sciences: lead
• Centers for Disease Control and Prevention: collaborator

Study Sites (1)

Malaria Alert Center, University of Malawi College of Medicine

Liwonde, Malawi

Location

Related Publications (1)

• Andronescu LR, Sharma A, Peterson I, Kachingwe M, Kachepa W, Liang Y, Gutman JR, Mathanga DP, Chinkhumba J, Laufer MK. The Effect of Intermittent Preventive Treatment of Malaria During Pregnancy and Placental Malaria on Infant Risk of Malaria. J Infect Dis. 2022 Jan 18;225(2):248-256. doi: 10.1093/infdis/jiab351.

  PMID: 34216212 DERIVED

MeSH Terms

Conditions

Malaria

Interventions

fanasil, pyrimethamine drug combination

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Study Officials

• Don P Mathanga, MBBS PhD

  Malawi College of Medicine

  PRINCIPAL INVESTIGATOR

• Julie Gutman, MD MSc

  Centers for Disease Control and Prevention

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical epidemiologist

Study Record Dates

• First Submitted: December 13, 2016
• First Posted: January 4, 2017
• Study Start: January 17, 2017
• Primary Completion: October 24, 2018
• Study Completion: October 24, 2018
• Last Updated: July 26, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: January 2022
• Access Criteria: IPD will be shared with other researches upon submission and approval of a detailed request

Locations

MA (1)