Efficacy and Safety of IPTp-DP Versus IPTp-SP in Malawi (STOPMIP-MW)

July 22, 2021 updated by: Julie Gutman, Kamuzu University of Health Sciences

A Prospective Randomized Open-Label Study on the Efficacy and Safety of Intermittent Preventive Treatment in Pregnancy (IPTp) With Dihydroartemisinin-Piperaquine (DP) Versus IPTp With Sulfadoxine-Pyrimethamine (SP) in Malawi

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Problem to be studied Malaria in pregnancy (MiP) due to Plasmodium falciparum infection is a major cause of maternal morbidity and poor birth outcomes in malaria-endemic countries. Pregnant women are at increased risk of more frequent and severe malaria infections than non-pregnant women. Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP), which involves administration of treatment doses of SP at each antenatal visit in the second and third trimesters of pregnancy, at least one month apart, irrespective of malaria parasitemia, is currently recommended for all women, except HIV positive women taking daily cotrimoxazole prophylaxis, in areas with stable moderate to high transmission of malaria.

SP is the only drug currently used for IPTp. Due to increasing resistance to SP, it is no longer used as a treatment for symptomatic malaria, however, IPTp-SP remains effective even in areas where SP resistance in children under five (determined by in vivo efficacy studies) is up to 26%, and continues to be used for IPTp in countries where SP is no longer recommended to treat symptomatic malaria. However, IPTp-SP has become more controversial given recent data from northern Tanzania and Malawi that have demonstrated that at higher rates of resistance, IPTp-SP may no longer be effective.

Alternative drugs which could replace SP have been tested; mefloquine, azithromycin-chloroquine, and amodiaquine have been abandoned as options due to poor tolerability among pregnant women. Dihydroartemisinin-Piperaquine (DP) remains an attractive option because of the long half-life of piperaquine (PQ) and the demonstrated efficacy, safety, and tolerability in pregnancy. Recent studies in Kenya and Uganda using DP for IPTp demonstrated a significant reduction in the prevalence of malaria throughout pregnancy and at the time of delivery. However, there was not a clear benefit in terms of improved neonatal outcomes. Additional studies are therefore needed to determine the impact of switching from IPTp-SP to IPTp-DP.

Study aims Primary objectives 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.

Secondary objectives

  • To determine if IPTp-DP results in decreased fetal morbidity compared with IPTp-SP, where fetal morbidity is defined as the composite of any of the following: Preterm birth (< 37 weeks gestation), low birth weight (LBW) (< 2,500 grams), or small for gestational age (SGA).
  • To evaluate the tolerability and safety of IPTp-DP in the second and third trimesters of pregnancy, including an assessment of cardiac risk, as measured by changes in QTc intervals from baseline with each successive dose.
  • To compare the frequency of adverse events and fetal congenital malformations in IPTp-DP with IPTp-SP.
  • To assess how SP and DP affect the maternal intestinal and vaginal microbiome.

Methodology Open-label, 2 arm randomized controlled superiority trial to compare the efficacy and safety of IPTp-DP to IPTp-SP in Malawi. The trial is designed to show a 60% decrease in malaria infection at delivery among HIV-negative women of all gravidity when IPTp-DP is used instead of IPTp-SP.

Expected findings and dissemination It is expected that in areas of high SP resistance, IPTp-DP will be superior to IPTp-SP in decreasing malaria infection at delivery. In addition, it is anticipated that DP will be well-tolerated among pregnant women and that fetal outcomes will be better than IPTp-SP.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
602

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Malawi
      • Liwonde, Malawi
        • Malaria Alert Center, University of Malawi College of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

16 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  • Previous inclusion in the same study
  • 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)
    • Antifungals (systemic): ketoconazole, fluconazole, itraconazole
    • Antiretrovirals: Saquinavir
    • Diuretics (e.g. hydrochlorothiazide, furosemide)
    • Antipsychotics (neuroleptics): haloperidol, thioridazine
    • Antidepressants: imipramine, citalopram, escitalopram
    • Antiemetics: domperidone, chlorpromazine, ondansetron

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Sulfadoxine-pyrimethamine
Intermittent preventive treatment with Sulfadoxine-pyrimethamine: Monthly dose of 3 co-formulated tablets containing 500 mg sulfadoxine and 25 mg pyrimethamine
Drug: Sulfadoxine-pyrimethamine
500 mg sulfadoxine and 25 mg pyrimethamine
Other Names:
  • Fansidar
Experimental: dihydroartemisinin-piperaquine

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
40 mg dihydroartemisinin and 320 mg piperaquine

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Malaria infection at the time of delivery
Time Frame: 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
Time Frame: Delivery
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Electrocardiogram changes following the receipt of DP
Time Frame: 4-6 hours after the 3rd dose with each course
QTc will be measured in a subset of women 4-6 hours after the 3rd dose of each course
4-6 hours after the 3rd dose with each course
Microbiome changes following receipt of DP or SP
Time Frame: From date of randomization until the date of delivery or last date of follow-up, average of ~4-5 months
We will measure the changes in the intestinal and vaginal microbiome induced by DP and 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
Time Frame: 3rd trimester
3rd trimester
Maternal anemia at 3rd trimester
Time Frame: 3rd trimester
3rd trimester
Fetal anemia
Time Frame: Delivery
Anemia/ hemoglobin measured from cord blood
Delivery
Incidence of clinical malaria episodes
Time Frame: From date of randomization until the date of delivery or last date of follow-up, average of ~4-5 months
From date of randomization until the date of delivery or last date of follow-up, average of ~4-5 months
Incidence of all cause sick visits
Time Frame: From date of randomization until the date of delivery or last date of follow-up, average of ~4-5 months
From date of randomization until the date of delivery or last date of follow-up, average of ~4-5 months
Serious adverse events
Time Frame: From date of randomization until the date of delivery or last date of follow-up, average of ~4-5 months
From date of randomization until the date of delivery or last date of follow-up, average of ~4-5 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Kamuzu University of Health Sciences

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Centers for Disease Control and Prevention

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Julie Gutman, MD MSc, Centers for Disease Control and Prevention
  • Principal Investigator: Don P Mathanga, MBBS PhD, Malawi College of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 17, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 24, 2018

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 24, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 13, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 30, 2016

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 4, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 26, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 22, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • MAC-P.02/16/1872

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

IPD will be shared with other researches upon submission and approval of a detailed request

IPD Sharing Time Frame

January 2022

IPD Sharing Access Criteria

IPD will be shared with other researches upon submission and approval of a detailed request

IPD Sharing Supporting Information Type

  • Study Protocol
  • Statistical Analysis Plan (SAP)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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