CQSP in Malawi: Chloroquine and Sulfadoxine-pyrimethamine Efficacy for the Treatment of Malaria in Malawi
Condition: Malaria; Plasmodium Falciparum Malaria
MeSH terms: Malaria; Malaria, Falciparum
Study type: Interventional
Phase: Phase 4

Summary: 
      The purpose of this research study is to find out how well chloroquine works as a drug to
      treat malaria in children, compared to the standard malaria treatment in Malawi. In
      preparation for a longer study of the malaria treatment medication chloroquine alone and in
      combination with other drugs, a shorter pre-study will be done to compare the anti-malarial
      effectiveness of chloroquine versus sulfadoxine-pyrimethamine (SP), the standard treatment in
      Malawi. Two hundred ten children, ages 6 months to 12 years, around Blantyre, Malawi, will be
      given standard dosing of either chloroquine or SP when they come to the Ndirande Health
      Centre with signs or symptoms consistent with malaria. The first 30 participants in each
      treatment group will remain under continuous observation at the health center so that the
      researchers can monitor their response to the medication until the infection goes away. The
      participants will be followed for 28 days to see if the the treatment works or fails.
    

Detailed description: 
      This study follows the observation that chloroquine-resistant malaria may have returned to
      Malawi, 10 years after its use was eliminated. There is growing consensus that combination
      chemotherapy should be the rule in malaria treatment to deter the development of drug
      resistance and possibly also decrease malaria transmission. As sulfadoxine-pyrimethamine (SP)
      failure rates increase, the reintroduction of chloroquine in Malawi in combination with
      highly effective rapidly acting drugs such as artesunate and chlorproguanil-dapsone should be
      considered, and would likely extend the useful life span of each of the drugs. In preparation
      for a longitudinal clinical trial of chloroquine alone and SP in combination with other
      drugs, a preliminary trial will be conducted to compare the anti-malarial efficacy of
      chloroquine versus SP, the standard treatment in Malawi. This is a randomized, open-label
      clinical trial to compare the antimalarial efficacy of chloroquine versus SP among children
      with uncomplicated malaria in Blantyre, Malawi. In this study, 210 peri-urban children will
      be randomly assigned to receive standard dosing of either chloroquine or SP. Follow up will
      consist of visits on days 2, 3, 7, 14, 21 and 28, according to the standard World Health
      Organization protocol. Because chloroquine has not been used to treat malaria in Malawi for
      over a decade, special safety precautions will be taken at the beginning of the study. The
      first 30 participants in each arm will remain at the Health Centre under continuous
      observation of the medical staff to monitor response to therapy until they are afebrile for
      12 hours and have two consecutive negative 12-hourly blood smears. Observation in an
      inpatient setting will also help to avoid potential bias due to more intense follow-up of the
      hospitalized group. A Safety Monitoring Committee (SMC) will meet after the first 30
      participants have been enrolled in each arm to determine if the study should stop continuous
      observation and proceed with out-patient follow up only. All participants will be followed
      for 28 days to monitor for late therapeutic or parasitologic failure. The primary study
      objective is to assess the efficacy of chloroquine compared with standard SP therapy, in
      treating malaria in Malawi, where chloroquine has not been used for over 10 years and to
      compare it to the efficacy of standard therapy with SP. The secondary study objective is to
      assess the effect of the re-introduction of chloroquine on the molecular markers associated
      with chloroquine resistance. The primary study endpoint is the rates of adequate clinical and
      parasitologic response to therapy. The secondary study endpoints are: (1) rates of early and
      late therapeutic failure; (2) rates of early and late parasitologic failure; (3) prevalence
      of chloroquine-resistance conferring pfcrt K76T mutation in pre-treatment infections; (4)
      rates of pre- and post-treatment pfcrt K76T mutation in cases of chloroquine treatment
      failure; (5) prevalence of SP-resistance conferring dhfr/dhps mutations in pre-treatment
      infections; (6) rates of pre- and post-treatment dhfr/dhps mutations in cases of SP treatment
      failure; (7) clearance time of parasitemia; (8) clearance time of fever; and (9) presence of
      post-treatment anemia.
    

Intervention name(s): chloroquine sulfate; sulfadoxine/pyrimethamine
Intervention type(s): Drug; Drug
Intervention MeSH terms: Chloroquine; Chloroquine diphosphate; Pyrimethamine; Sulfadoxine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: chloroquine, malaria, sulfadoxine/pyrimethamine, Malawi