Improving PRegnancy Outcomes With Intermittent preVEntive Treatment in Africa (IMPROVE)

Liverpool School of Tropical Medicine

Status and phase: Completed; Phase 3

Conditions: Malaria; Malaria in Pregnancy; Pregnancy

Treatments: Drug: sulphadoxine-pyrimethamine; Drug: dihydroartemisinin-piperaquine; Drug: dihydroartemisinin-piperaquine plus azithromycin

Study type: Interventional

Funder types: Other; Other U.S. Federal agency

Identifiers

NCT03208179

16.049

Details and patient eligibility

About

This study evaluates the efficacy and safety of monthly intermittent preventive treatment using dihydroartemisinin piperaquine (DP) alone or in combination with azithromycin (AZ) compared to sulphadoxine-pyrimethamine (SP) for the prevention of malaria in pregnant women in the second and third trimester.

Full description

Intermittent preventive treatment with sulphadoxine-pyrimethamine (IPTp-SP) is one of the pillars of malaria prevention in pregnancy in sub-Saharan Africa, in addition to prompt case management and use of long lasting insecticide treated bednets. However, mounting resistance to SP by Plasmodium falciparum increasing renders IPTP-SP ineffective.

Two exploratory trials in Uganda and Kenya demonstrated that IPTp with DP was superior to IPTp-SP for the prevention of malaria infection in pregnancy. However, neither study was adequately powered to look at adverse birth outcomes. This study is a confirmatory efficacy trial in Malawi, Tanzania and Kenya to determine the efficacy and safety of IPTp with DP alone or in combination with AZ.

This will be a 3-arm trial, superiority, partial blinded, placebo controlled, randomized trial comparing IPTp with SP, versus IPTp with DP alone, and IPTp with DP+AZ with the following hypotheses:

• IPTp with DP is superior to IPTp with SP in preventing adverse pregnancy outcomes.
• The combination of DP with AZ further reduces adverse pregnancy outcomes compared to IPTp with DP alone.

Enrollment: 4,680 patients

Sex: Female

Ages: 16+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Pregnant women between 16-28 weeks' gestation
• Viable singleton pregnancy
• Resident of the study area
• Willing to adhere to scheduled and unscheduled study visit procedures
• Willing to deliver in a study clinic or hospital
• Provide written informed consent

Exclusion criteria

• Multiple pregnancies (i.e. twin/triplets)
• HIV-positive
• Known heart ailment
• Severe malformations or non-viable pregnancy if observed by ultrasound
• History of receiving IPTp-SP during this current pregnancy
• Unable to give consent
• Known allergy or contraindication to any of the study drugs

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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4,680 participants in 3 patient groups

IPTp-SP

Active Comparator group

Description:

Stat course of 3 tablets of quality-assured SP (tablets of 500 mg of sulphadoxine and 25 mg of pyrimethamine) at each scheduled antenatal visit

Treatment:

Drug: sulphadoxine-pyrimethamine

IPTp-DP

Experimental group

Description:

Dihydroartemisinin-piperaquine \[3 to 5 tablets of DP (tablets of 40 mg of dihydroartemisinin and 320 mg of piperaquine, based on bodyweight) daily for 3 days\] + placebo AZ at each scheduled antenatal visit

Treatment:

Drug: dihydroartemisinin-piperaquine

IPTp-DPAZ

Experimental group

Description:

Dihydroartemisinin-piperaquine \[3 to 5 tablets of DP (tablets of 40 mg of dihydroartemisinin and 320 mg of piperaquine, based on bodyweight) daily for 3 days\] + AZ tablet \[1.5g over 3 days as 500mg per day\] at each scheduled antenatal visit.

Treatment:

Drug: dihydroartemisinin-piperaquine plus azithromycin