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PregnancyPhase 4STOP MiP KENYANCT01669941

Efficacy of Intermittent Screening and Treatment or Intermittent Preventive Treatment (IPT) With Dihydroartemisinin-Piperaquine, Versus IPT With Sulfadoxine-Pyrimethamine for the Control of Malaria in Pregnancy in Kenya

A Phase 4 study testing IPTp-SP, IPTp-DP and ISTp-DP in people with Pregnancy and Malaria, run by Kenya Medical Research Institute at 4 sites in Kenya.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Malaria in pregnancy (MiP) due to Plasmodium falciparum infection is a major cause of maternal morbidity and poor birth outcomes. Intermittent preventive treatment in pregnancy (IPTp) with Sulfadoxine pyrimethamine (SP), the administration of SP at predefined intervals in the second and third trimesters of pregnancy… Read more about this study

Who is it for?
Any age, women only
Conditions the study is for
Pregnancy, Malaria
What is being tested?
IPTp-SP, IPTp-DP and ISTp-DP
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,546 participants
Where
4 sitesKenya
Study dates
Aug 2012to Dec 2015
Phase
Phase 4
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 Any age
  • Women only
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Viable pregnancy assessed by Doppler
  • Gestational age 16 to 32 weeks (inclusive) by fundal height
  • No history of IPTp use during this pregnancy
  • Willing to participate and complete the study schedule
  • 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
  • Willing to deliver in the labor ward of the study clinic or hospital
  • HIV negative at enrolment

Who cannot join

  • HIV positive or unknown
  • Residence outside study area or planning to move out in the 12 months following enrolment
  • 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
  • Unable to give informed consent (for example due to mental disability)
Show all 12Show fewer
  • Previous inclusion in the same study
  • Gestational age >32 weeks
  • Previous IPTp during the current pregnancy
  • Participating in other malaria intervention studies
  • Known or suspected cardiac disease
  • Patients taking drugs in any of the following classes: antiarrhythmic agents, neuroleptics, macrolides, and certain antimalarial drugs such as mefloquine, chloroquine, halofantrine and lumefantrine.

Trial locations and contacts

4 sites in 1 country.

Kenya4 sites

  • Bondo District Hospital

    Bondo, Bondo, 40601

  • Madiany sub-District Hospital

    Madiany

  • Lwak Mission Hospital

    Rarieda, Nyanza

  • Siaya District Hospital

    Siaya, Nyanza, 40600

Other trials in Kenya

About this study

Official title: Intermittent Screening and Treatment (IST) or Intermittent Preventive Treatment (IPT) With Dihydroartemisinin-Piperaquine, Versus IPT With Sulfadoxine-Pyrimethamine for the Control of Malaria in Pregnancy in Kenya: a Randomized Controlled Trial

Malaria in pregnancy (MiP) due to Plasmodium falciparum infection is a major cause of maternal morbidity and poor birth outcomes. Intermittent preventive treatment in pregnancy (IPTp) with Sulfadoxine pyrimethamine (SP), the administration of SP at predefined intervals in the second and third trimesters of pregnancy irrespective of the presence of malaria parasitemia, is currently recommended for HIV-negative women in all areas with stable moderate to high transmission of malaria. Due to increasing resistance to SP, it is no longer used as a treatment for symptomatic malaria, and the efficacy of IPTp-SP seems to be decreased. This study aims to look at a new drug, Dihydroartemisinin-Piperaquine (DP) for IPTp, as well as to explore the strategy of intermittent screening and treatment in pregnancy (ISTp) with DP. This strategy uses increased screening at time of focused antenatal care (FANC) with treatment of women who screen positive.

The hypothesis is that the efficacy of both IPTp-DP and ISTp-DP will be associated with a reduction in malaria infection at delivery among HIV(-) women when compared to IPTp-SP, in an area with decreasing malaria transmission and high levels of SP resistance in Kenya.

Read the detailed description

Malaria in pregnancy (MiP) due to Plasmodium falciparum infection is a major cause of maternal morbidity and poor birth outcomes. Pregnant women are at increased risk of more frequent and severe malaria infections than are non-pregnant women. Intermittent preventive treatment in pregnancy (IPTp), the administration of treatment doses of an antimalarial at predefined intervals in the second and third trimesters of pregnancy irrespective of the presence of malaria parasitemia, is currently recommended for HIV-negative women in all areas with stable moderate to high transmission of malaria. The strategy is thought to work by providing intermittent clearance or suppression of parasites in the placenta, and preventing new infections from occurring through the prophylactic effect of the recommended drug for IPTp, sulfadoxine-pyrimethamine (SP).

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 with SP remains effective even in areas where SP resistance in children under five (determined by in vivo efficacy studies) is up to 26%. SP therefore continues to be used for IPTp in many countries where it is no longer used for treatment of symptomatic malaria. However, more recent data from northern Tanzania and Malawi indicate that at higher rates of resistance, IPTp-SP may no longer be effective, and could potentially be harmful.

In view of this data, a search for alternatives to IPTp-SP is warranted. One strategy would be to choose a different drug for IPTp. Of the available combinations, Dihydroartemisinin-Piperaquine (DP) remains one of the most attractive options because of the long half-life of piperaquine (PQ) and the demonstrated efficacy and safety in pregnancy. Another strategy to consider is intermittent screening and treatment in pregnancy (ISTp), whereby there is increased screening at time of focused antenatal care (FANC) with treatment of women who screen positive. The same properties (long half-life, tolerability, safety, once daily dosing) which make DP a good choice for IPTp also make it one of the best available options for ISTp.

This study aims to compare the efficacy of IPTp-SP against that of IPTp-DP and ISTp-DP to determine if these alternate strategies are associated with a reduction in malaria infection at delivery among HIV(-) women in an area with decreasing malaria transmission and high levels of SP resistance in Kenya.

Conditions
Pregnancy, Malaria
Being tested
IPTp-SP, IPTp-DP, ISTp-DP
Keywords
Pregnancy, Plasmodium, Malaria, Prevention, Kenya, Piperaquine, 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.

  • IPTp-SPDrug

    Also called Fansidar, SP

    3 tablets of sulfadoxine (500 mg) and pyrimethamine (25 mg) given at each ANC visit

  • IPTp-DPDrug

    Also called Eurartesim, Duocotexin

    At each ANC visit: treatment with Dihydroartemisinin-piperaquine for three days, with the daily number of tablets depending on the weight of the woman; two tablets for women weighing 24- 35.9kg, three tablets for women weighing 36 to 74.9 kg, and four tablets for women weighing 75kg or more. The first dose will be observed; the woman will be given the additional 2 doses to take at home and there may be a home visit to confirm that the tablets were taken.

  • ISTp-DPDrug

    Also called Eurartesim, Duocotexin

    At each ANC visit, women will be screened for malaria using a combined HRP-2/ pLDH (P. falciparum/ pan-malaria) rapid diagnostic test, and if positive, treated with dihydroartemisinin-piperaquine. Each tablet will contain 40 mg dihydroartemisinin and 320 mg piperaquine. Treatment will be given for three days, with the daily number of tablets depending on the weight of the woman; two tablets for women weighing 24- 35.9kg, three tablets for women weighing 36 to 74.9 kg, and four tablets for women weighing 75kg or more. The first dose will be observed; the woman will be given the additional 2 doses to take at home

Study groups in NCT01669941
Study groupRoleWhat they receive
IPTp-DPExperimentalAt each ANC visit, women will be given treatment with Dihydroartemisinin-piperaquine for three days, with the daily number of tablets depending on the weight of the woman; two tablets for women weighing 24- 35.9kg, three tablets for women weighing 36 to 74.9 kg, and four tablets for women weighing 75kg or more. The first dose will be observed; the woman will be given the additional 2 doses to take at home and there may be a home visit to confirm that the tablets were taken.
Receives: Drug: IPTp-DP
ISTp-DPExperimentalAt each ANC visit, women will be screened for malaria using a combined HRP-2/ pLDH (P. falciparum/ pan-malaria) rapid diagnostic test, and if they test positive, will be treated with dihydroartemisinin-piperaquine (DP). Each tablet will contain 40 mg dihydroartemisinin and 320 mg piperaquine. Treatment will be given for three days, with the daily number of tablets depending on the weight of the woman; two tablets for women weighing 24- 35.9kg, three tablets for women weighing 36 to 74.9 kg, and four tablets for women weighing 75kg or more. The first dose will be observed; the woman will be given the additional 2 doses to take at home
Receives: Drug: ISTp-DP
IPTp-SPActive comparatorTreatment with a single dose of three tablets of sulfadoxine-pyrimethamine, each containing sulfadoxine (500 mg) and pyrimethamine (25 mg) at each FANC visit. This is the standard regimen.
Receives: Drug: IPTp-SP

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maternal malaria at delivery

    Active or recent infection at delivery measured as the composite of peripheral and placental malaria, detected by: positive peripheral blood smear or RDT or positive placental smear, RDT, or histopathology

    Measured: Delivery

Secondary outcomes (5)

  1. Decreased fetal morbidity

    Decreased fetal morbidity, defined as the composite of 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) defined as a binary outcome of <10th percentile of fetal weight for attained gestational age using the Landis fetal weight nomogram from the Democratic Republic of Congo

    Measured: Delivery

  2. Frequency of fetal congenital malformations

    Measured: At delivery

  3. Pharmacokinetics- piperaquine level

    Measured: At baseline, and day 2 and day 7 following dosing.

  4. level of antibodies to variant surface antigens (VSAs)

    Measured: At delivery

  5. Frequency of maternal adverse events

    Measured: At each ANC visit and at delivery

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Aug 2012 (estimated)
  2. Study startAug 2012
  3. Primary completionOct 2014
  4. Study completionDec 2015

Resources

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 4
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
1,546 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01669941
Sponsor's protocol ID
STOPMiP-KENYA
Acronym
STOP MiP KENYA
Status last verified
Mar 2017
First submitted
15 Aug 2012
Last updated
6 Mar 2017
Results posted
No
Data monitoring committee
Yes

Publications

  • Chotsiri P, Gutman JR, Ahmed R, Poespoprodjo JR, Syafruddin D, Khairallah C, Asih PBS, L'lanziva A, Otieno K, Kariuki S, Ouma P, Were V, Katana A, Price RN, Desai M, Ter Kuile FO, Tarning J. Piperaquine Pharmacokinetics during Intermittent Preventive Treatment for Malaria in Pregnancy. Antimicrob Agents Chemother. 2021 Feb 17;65(3):e01150-20. doi: 10.1128/AAC.01150-20. Print 2021 Feb 17.

    PubMed 33361303

  • Desai M, Gutman J, L'lanziva A, Otieno K, Juma E, Kariuki S, Ouma P, Were V, Laserson K, Katana A, Williamson J, ter Kuile FO. Intermittent screening and treatment or intermittent preventive treatment with dihydroartemisinin-piperaquine versus intermittent preventive treatment with sulfadoxine-pyrimethamine for the control of malaria during pregnancy in western Kenya: an open-label, three-group, randomised controlled superiority trial. Lancet. 2015 Dec 19;386(10012):2507-19. doi: 10.1016/S0140-6736(15)00310-4. Epub 2015 Sep 28.

    PubMed 26429700

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing IPTp-SP, IPTp-DP and ISTp-DP in people with Pregnancy and Malaria, run by Kenya Medical Research Institute at 4 sites in Kenya.

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 12 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 6 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in Kenya. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

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?

Maternal malaria at delivery (time frame: Delivery). 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 NCT01669941, which also lists 2 linked publications.

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 6 Mar 2017.

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