MalariaPhase 3STOPMIP-MWNCT03009526
Efficacy and Safety of IPTp-DP Versus IPTp-SP in Malawi
A Phase 3 study testing Sulfadoxine-pyrimethamine and dihydroartemisinin-piperaquine in people with Malaria and Pregnancy, run by Kamuzu University of Health Sciences at 1 site in Malawi.
Trial 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. Read more about this study
- Who is it for?
- Ages 16 years and older, women onlyHealthy volunteers can take part
- What is being tested?
- Sulfadoxine-pyrimethamine and dihydroartemisinin-piperaquine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 602 participants
- Where
- 1 siteMalawi
- Study dates
- 17 Jan 2017to 24 Oct 2018
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 years and older
- Women only
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 22Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Malawi1 site
Malaria Alert Center, University of Malawi College of Medicine
Liwonde
About this study
Official title: 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.
Read the 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.
- Being tested
- Sulfadoxine-pyrimethamine, dihydroartemisinin-piperaquine
- Keywords
- Malaria, Pregnancy, Malawi, Intermittent preventive treatment, dihydroartemisinin-piperaquine, sulfadoxine-pyrimethamine
- Medical subject headings
- Malaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sulfadoxine-pyrimethamineDrug
Also called Fansidar
500 mg sulfadoxine and 25 mg pyrimethamine
dihydroartemisinin-piperaquineDrug
40 mg dihydroartemisinin and 320 mg piperaquine
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Drug: dihydroartemisinin-piperaquine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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)
Measured: Delivery
Secondary outcomes (8)
Electrocardiogram changes following the receipt of DP
QTc will be measured in a subset of women 4-6 hours after the 3rd dose of each course
Measured: 4-6 hours after the 3rd dose with each course
Microbiome changes following receipt of DP or SP
We will measure the changes in the intestinal and vaginal microbiome induced by DP and SP
Measured: 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
Measured: 3rd trimester
Maternal anemia at 3rd trimester
Measured: 3rd trimester
Fetal anemia
Anemia/ hemoglobin measured from cord blood
Measured: Delivery
Incidence of clinical malaria episodes
Measured: 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
Measured: From date of randomization until the date of delivery or last date of follow-up, average of ~4-5 months
Serious adverse events
Measured: From date of randomization until the date of delivery or last date of follow-up, average of ~4-5 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jan 2017 (estimated)
- Study start17 Jan 2017
- Primary completion24 Oct 2018
- Study completion24 Oct 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for MalariaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 602 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kamuzu University of Health Sciences
- Sponsor type
- University, hospital or other
- Collaborators
- Centers for Disease Control and Prevention
- Responsible party
- Principal investigator, Julie Gutman, Kamuzu University of Health Sciences
- Investigators
- Don P Mathanga, MBBS PhD, Principal investigator, Malawi College of MedicineJulie Gutman, MD MSc, Principal investigator, Centers for Disease Control and Prevention
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03009526
- Sponsor's protocol ID
- MAC-P.02/16/1872
- Acronym
- STOPMIP-MW
- Status last verified
- Jul 2021
- First submitted
- 13 Dec 2016
- Last updated
- 26 Jul 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: IPD will be shared with other researches upon submission and approval of a detailed request
Publications
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.
PubMed 34216212
Study at a glance
From the registry record, last updated by the sponsor on 26 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT03009526
- Acronym / sponsor ID
- STOPMIP-MW / MAC-P.02/16/1872
- Keywords
- Malaria, Pregnancy, Malawi, Intermittent preventive treatment, dihydroartemisinin-piperaquine, sulfadoxine-pyrimethamine
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 602 participants (actual)
- Lead sponsor
- Kamuzu University of Health SciencesUniversity, hospital or other
- Collaborators
- Centers for Disease Control and Prevention
- Study start
- 17 Jan 2017 (actual)
- Primary completion
- 24 Oct 2018 (actual)
- Study completion
- 24 Oct 2018 (actual)
- First posted
- 4 Jan 2017 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sulfadoxine-pyrimethamine | Active comparator | Drug: Sulfadoxine-pyrimethamineIntermittent preventive treatment with Sulfadoxine-pyrimethamine: Monthly dose of 3 co-formulated tablets containing 500 mg sulfadoxine and 25 mg pyrimethamine |
| dihydroartemisinin-piperaquine | Experimental | Drug: dihydroartemisinin-piperaquineIntermittent 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 |
Who may qualify
- Ages
- 16 years and older
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (22 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sulfadoxine-pyrimethamineAlso: Fansidar500 mg sulfadoxine and 25 mg pyrimethamine | Drug | Sulfadoxine-pyrimethamine |
| dihydroartemisinin-piperaquine40 mg dihydroartemisinin and 320 mg piperaquine | Drug | dihydroartemisinin-piperaquine |
Primary outcome
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
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)
8 secondary outcomes
Electrocardiogram changes following the receipt of DP
Time frame: 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
Maternal hemoglobin at 3rd trimester
Time frame: 3rd trimester
Maternal anemia at 3rd trimester
Time frame: 3rd trimester
Fetal anemia
Time frame: 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
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
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jul 2021.
- Derived from this study: PubMed 34216212Andronescu 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.
- Individual participant dataSharing planned: Yes. IPD will be shared with other researches upon submission and approval of a detailed request
Related trials for Malaria
Not yet recruiting
Positron Emission Tomography and Organ-Specific Changes in Participants Co-Enrolled in NIH Studies of Plasmodium Vivax Controlled Human Malaria Infection
Healthy Volunteer, Malaria
RecruitingObservational study
Host and Parasite Factors That Influence Susceptibility to Malaria Infection and Disease During Pregnancy and Early Childhood in Ouelessebougou and Bamako, Mali
Malaria
RecruitingPhase 1
Induced Blood-Stage Malaria in Healthy Malaria-Naive Adults to Assess the Safety and Infectivity of Plasmodium Vivax Challenge Agent and Evaluate Transmission in Mosquito Feeding Assays
Malaria
RecruitingPhase 1/2
DON in Pediatric Cerebral Malaria
Malaria, Cerebral
Not yet recruitingPhase 1
Safety and Immunogenicity of the Recombinant Malaria Vaccines in Healthy Adults Aged 18-50 Years
Malaria Vaccine
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Don P Mathanga, MBBS PhD principal investigator
Malawi College of Medicine
Julie Gutman, MD MSc principal investigator
Centers for Disease Control and Prevention
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Sulfadoxine-pyrimethamine and dihydroartemisinin-piperaquine in people with Malaria and Pregnancy, run by Kamuzu University of Health Sciences at 1 site in Malawi.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Malawi. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Malaria infection at the time of delivery (time frame: delivery). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03009526, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jul 2021.