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 (STOP MiP KENYA)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Liverpool School of Tropical Medicine
London School of Hygiene and Tropical Medicine
Information provided by (Responsible Party):
Abraham Katana, MD, Kenya Medical Research Institute
ClinicalTrials.gov Identifier:
NCT01669941
First received: August 15, 2012
Last updated: May 6, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Pregnancy
Malaria
Drug: IPTp-SP
Drug: IPTp-DP
Drug: ISTp-DP
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
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

Resource links provided by NLM:


Further study details as provided by Kenya Medical Research Institute:

Primary Outcome Measures:
  • Maternal malaria at delivery [ Time Frame: Delivery ] [ Designated as safety issue: No ]
    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


Secondary Outcome Measures:
  • Decreased fetal morbidity [ Time Frame: Delivery ] [ Designated as safety issue: No ]

    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

  • Frequency of fetal congenital malformations [ Time Frame: At delivery ] [ Designated as safety issue: Yes ]
  • Pharmacokinetics- piperaquine level [ Time Frame: At baseline, and day 2 and day 7 following dosing. ] [ Designated as safety issue: No ]
  • level of antibodies to variant surface antigens (VSAs) [ Time Frame: At delivery ] [ Designated as safety issue: No ]
  • Frequency of maternal adverse events [ Time Frame: At each ANC visit and at delivery ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 1554
Study Start Date: August 2012
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: IPTp-DP
At 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.
Drug: IPTp-DP
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.
Other Names:
  • Eurartesim
  • Duocotexin
Experimental: ISTp-DP
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 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
Drug: ISTp-DP
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
Other Names:
  • Eurartesim
  • Duocotexin
Active Comparator: IPTp-SP
Treatment 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.
Drug: IPTp-SP
3 tablets of sulfadoxine (500 mg) and pyrimethamine (25 mg) given at each ANC visit
Other Names:
  • Fansidar
  • SP

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.

  Eligibility

Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Viable pregnancy assessed by Doppler
  2. Gestational age 16 to 32 weeks (inclusive) by fundal height
  3. No history of IPTp use during this pregnancy
  4. Willing to participate and complete the study schedule
  5. Willing to sign or thumb print informed consent
  6. Resident of study area and intending to stay in the area for the duration of the follow-up
  7. Willing to deliver in the labor ward of the study clinic or hospital
  8. HIV negative at enrolment

Exclusion Criteria:

  1. HIV positive or unknown
  2. Residence outside study area or planning to move out in the 12 months following enrolment
  3. 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)
  4. Severe anemia requiring blood transfusion (Hb ≤ 7.0 g/dL) at enrolment
  5. Known allergy or previous adverse reaction to any of the study drugs
  6. Unable to give informed consent (for example due to mental disability)
  7. Previous inclusion in the same study
  8. Gestational age >32 weeks
  9. Previous IPTp during the current pregnancy
  10. Participating in other malaria intervention studies
  11. Known or suspected cardiac disease
  12. Patients taking drugs in any of the following classes: antiarrhythmic agents, neuroleptics, macrolides, and certain antimalarial drugs such as mefloquine, chloroquine, halofantrine and lumefantrine.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01669941

Locations
Kenya
Lwak Mission Hospital
Rarieda, Nyanza, Kenya
Siaya District Hospital
Siaya, Nyanza, Kenya, 40600
Bondo District Hospital
Bondo, Kenya, 40601
Madiany sub-District Hospital
Madiany, Kenya
Sponsors and Collaborators
Kenya Medical Research Institute
Liverpool School of Tropical Medicine
London School of Hygiene and Tropical Medicine
Investigators
Principal Investigator: Meghna Desai, PhD MPH Centers for Disease Control and Prevention
Principal Investigator: Abraham Katana, MD Kenya Medical Research Institute
  More Information

No publications provided

Responsible Party: Abraham Katana, MD, Medical Officer, Kenya Medical Research Institute
ClinicalTrials.gov Identifier: NCT01669941     History of Changes
Other Study ID Numbers: STOPMiP-KENYA
Study First Received: August 15, 2012
Last Updated: May 6, 2014
Health Authority: United States: Federal Government
Kenya: Ethical Review Committee
Kenya: Pharmacy and Poisons Board

Keywords provided by Kenya Medical Research Institute:
Pregnancy
Plasmodium
Malaria
Prevention
Kenya
Piperaquine
Dihydroartemisinin-Piperaquine
Sulfadoxine Pyrimethamine

Additional relevant MeSH terms:
Malaria
Parasitic Diseases
Protozoan Infections
Artemisinins
Dihydroartemisinin
Fanasil, pyrimethamine drug combination
Piperaquine
Pyrimethamine
Sulfadoxine
Anti-Infective Agents
Anti-Infective Agents, Urinary
Antimalarials
Antiparasitic Agents
Antiprotozoal Agents
Enzyme Inhibitors
Folic Acid Antagonists
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Renal Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014