Chemopreventive Therapy for Malaria in Ugandan Children (PROMOTE-Chemop)
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ClinicalTrials.gov Identifier: NCT00948896 |
Recruitment Status :
Completed
First Posted : July 29, 2009
Results First Posted : August 4, 2015
Last Update Posted : November 24, 2015
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Malaria | Drug: trimethoprim-sulfamethoxazole (TS; TMP/SMX) Drug: sulfadoxine-pyrimethamine (SP) Drug: dihydroartemisinin-piperaquine (DP) | Phase 3 |
Convenience sampling will be used to enroll a cohort of 600 HIV-uninfected infants between the ages of 4-5 months of age according to the following strata based on the mother's HIV status: 1) 200 HIV-exposed infants born to HIV-infected mothers, and 2) 400 HIV-unexposed infants born to HIV-uninfected mothers. Potential study participants will be identified from the Tororo District Hospital Antenatal Clinic and surrounding clinics providing routine pediatric care. Potential study participants less than 6 months of age and their parents/guardians will be referred to our study clinic for screening. Eligible children will be enrolled when they reach 4-5 months of age and followed until the age of 36 months for all their routine medical care at our designated study clinic. All mother-child pairs will receive 2 long lasting ITNs at enrollment and, as available, a basic care package including a safe water vessel, multivitamins and condoms. HIV-unexposed children will be randomized to one of four chemoprevention arms when they reach 6 months of age. All HIV-exposed children born to HIV-infected mothers will be given TS prophylaxis and mothers will be encouraged to introduce food at 6 months of life and continue breastfeeding until 1 year of life, in accordance with Ugandan Ministry of Health (MOH) guidelines. HIV-exposed children will retested for HIV approximately every 60 days during breastfeeding and 6 weeks following cessation of breastfeeding. HIV-exposed children who remain HIV-uninfected following cessation of breastfeeding will be randomized to one of four chemoprevention arms. HIV-exposed children who test positive for HIV during the course of the study (those who seroconvert during breastfeeding) will be excluded from the study and referred for appropriate care.
During the follow-up period, all patients presenting to the clinic with a new episode of fever will undergo standard evaluation (history, physical examination and Giemsa-stained blood smear) for the diagnosis of malaria. Children diagnosed with uncomplicated malaria will be treated with AL and children diagnosed with complicated malaria will be treated with quinine in accordance with national guidelines. Response to antimalarial therapy will be assessed using standardized guidelines. All AL treatment failures occurring within 14 days of diagnosis will be treated with quinine in accordance with national guidelines. In the event that a patient fails quinine therapy, therapy will be repeated with quinine plus clindamycin. Patients with complicated malaria who have contraindications to giving quinine will be treated with parenteral artesunate. All episodes diagnosed more than 14 days after a previous episode will be considered new episodes for treatment purposes. After two years of age, patients with uncomplicated malaria will have follow up visits on the days Antimalarial drugs are administered only (Day 0, 1, and 2). Routine assessments will be performed in the study clinic approximately every 30 days. Routine assessments will include review of study protocol with parents/guardians of study participants, assessment for any outside medical care, assessment for adherence to assigned chemopreventive therapy, a focused history and physical examination and routine blood smears for the detection of asymptomatic parasitemia. Routine phlebotomy will be performed approximately every 120 days for all study participants for CBC, glucose and ALT measurements.
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 600 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Prevention |
Official Title: | A Randomized Controlled Trial of Monthly Dihydroartemisinin-piperaquine Versus Monthly Sulfadoxine-pyrimethamine Versus Daily Trimethoprim-sulfamethoxazole Versus No Therapy for the Prevention of Malaria |
Study Start Date : | June 2010 |
Actual Primary Completion Date : | April 2014 |
Actual Study Completion Date : | April 2014 |
Arm | Intervention/treatment |
---|---|
Experimental: 1 |
Drug: trimethoprim-sulfamethoxazole (TS; TMP/SMX)
daily dosing, 20mgTMP/100mgSMX tabs, 80mgTMP/400mgSMX tabs |
Experimental: 2 |
Drug: sulfadoxine-pyrimethamine (SP)
monthly dosing given as a single dose, 500mg/25mg tabs |
Experimental: 3 |
Drug: dihydroartemisinin-piperaquine (DP)
monthly dosing given once a day for 3 consecutive days, 40mg/320mg tabs |
No Intervention: 4 |
- Incident Malaria Cases Per Person Year at Risk in HIV-unexposed Participants [ Time Frame: 6 to 24 months of age ]The incidence of malaria, defined as the number of incident episodes per time at risk, during the period the intervention was given (6-24 mo of age). Treatments within 14d of a prior episode were not considered incident events. Time at risk was from the day following the initiation of study drugs to the last day of observation, minus 14 d after each treatment for malaria.
- Incident Malaria Cases Per Person Year at Risk in HIV-exposed Participants [ Time Frame: Randomization to 24 months of age ]The primary outcome was the incidence of malaria, defined as the number of incident episodes per time at risk, during the period the intervention was given. Treatments within 14 days of a prior episode were not considered incident events. Time at risk was from the day following the initiation of study drugs to the last day of observation, minus 14 days after each treatment for malaria.
- Incidence of Any Adverse Events Defined as Severity Grade 3-4 That Are Possibly, Probably, or Definitely Related to Study Drugs [ Time Frame: Time from randomization until 24 months of age ]NIH Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events published December, 2004
- Rebound Incidence of Malaria Defined as the Number of Treatments for New Episodes of Malaria Per Time at Risk [ Time Frame: 24 months to 36 months of age ]

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Ages Eligible for Study: | 4 Months to 5 Months (Child) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | Yes |
Inclusion Criteria:
- Age 4 -5 months
- Confirmed HIV status of biological mother
- Negative HIV DNA PCR test at time of enrollment for infants born to HIV-infected mothers
- Infants born to HIV-infected mothers must be breastfeeding
- Residency within 30km of the study clinic
- Agreement to come to the study clinic for any febrile episode or other illness and avoid medications given outside the study protocol
- Provision of informed consent by parent/guardian
Exclusion Criteria:
- History of allergy or sensitivity to TS, SP, or DP
- Active medical problem requiring in-patient evaluation at the time of screening
- Intention of moving more that 30km from the study clinic during the follow-up period
- Chronic medical condition (i.e. malignancy) requiring frequent medical attention
- Living in the same household as a previously enrolled study participant
- QTc interval > 450 msec
- Other clinically significant ECG abnormalities such as arrhythmia, ischemia, or evidence of heart failure
- Family history of Long QT syndrome
- Current use of drugs that prolong the QT interval

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00948896
Uganda | |
IDRC Research Clinic -Tororo District Hospital | |
Tororo, Uganda |
Study Director: | Diane V. Havlir, MD | University of California, San Francisco | |
Principal Investigator: | M. Grant Dorsey, MD, PhD | University of California, San Francisco | |
Principal Investigator: | Moses R Kamya MBChB, MMed, MPH | Makerere University; IDRC |
Publications of Results:
Responsible Party: | Grant Dorsey, M.D, Ph.D., Associate Professor, University of California, San Francisco |
ClinicalTrials.gov Identifier: | NCT00948896 |
Other Study ID Numbers: |
H9926-33953 NIH P01HD059454 2009-077 ( Other Identifier: Makerere Univ Fac of Med Research and Ethics Committee ) HS-580 ( Other Identifier: Uganda National Council for Science and Tech ) 686/ESR/NDA/DID-11/2009 ( Other Identifier: Uganda National Drug Authority ) H9926-33953 and 10-01489 ( Other Identifier: UCSF Committee on Human Research ) |
First Posted: | July 29, 2009 Key Record Dates |
Results First Posted: | August 4, 2015 |
Last Update Posted: | November 24, 2015 |
Last Verified: | October 2015 |
Chemoprevention Uganda Malaria |
Trimethoprim-sulfamethoxazole Sulfadoxine-pyrimethamine Dihydroartemisinin-piperaquine |
Malaria Protozoan Infections Parasitic Diseases Infections Vector Borne Diseases Pyrimethamine Piperaquine Sulfadoxine Trimethoprim Fanasil, pyrimethamine drug combination Artenimol Trimethoprim, Sulfamethoxazole Drug Combination Sulfamethoxazole |
Antimalarials Antiprotozoal Agents Antiparasitic Agents Anti-Infective Agents Folic Acid Antagonists Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-Infective Agents, Urinary Renal Agents Anti-Dyskinesia Agents Cytochrome P-450 CYP2C8 Inhibitors Cytochrome P-450 Enzyme Inhibitors Anti-Bacterial Agents |