- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00948896
Chemopreventive Therapy for Malaria in Ugandan Children (PROMOTE-Chemop)
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 Overview
Status
Conditions
Detailed Description
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
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
-
-
-
Tororo, Uganda
- IDRC Research Clinic -Tororo District Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 1
|
daily dosing, 20mgTMP/100mgSMX tabs, 80mgTMP/400mgSMX tabs
|
Experimental: 2
|
monthly dosing given as a single dose, 500mg/25mg tabs
|
Experimental: 3
|
monthly dosing given once a day for 3 consecutive days, 40mg/320mg tabs
|
No Intervention: 4
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
6 to 24 months of age
|
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.
|
Randomization to 24 months of age
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
Time from randomization until 24 months of age
|
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
|
24 months to 36 months of age
|
Collaborators and Investigators
Collaborators
Investigators
- 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 and helpful links
General Publications
- Osterbauer B, Kapisi J, Bigira V, Mwangwa F, Kinara S, Kamya MR, Dorsey G. Factors associated with malaria parasitaemia, malnutrition, and anaemia among HIV-exposed and unexposed Ugandan infants: a cross-sectional survey. Malar J. 2012 Dec 27;11:432. doi: 10.1186/1475-2875-11-432.
- Ochong E, Tumwebaze PK, Byaruhanga O, Greenhouse B, Rosenthal PJ. Fitness Consequences of Plasmodium falciparum pfmdr1 Polymorphisms Inferred from Ex Vivo Culture of Ugandan Parasites. Antimicrob Agents Chemother. 2013 Sep;57(9):4245-4251. doi: 10.1128/AAC.00161-13. Epub 2013 Jun 24.
- Marquez C, Okiring J, Chamie G, Ruel TD, Achan J, Kakuru A, Kamya MR, Charlebois ED, Havlir DV, Dorsey G. Increased morbidity in early childhood among HIV-exposed uninfected children in Uganda is associated with breastfeeding duration. J Trop Pediatr. 2014 Dec;60(6):434-41. doi: 10.1093/tropej/fmu045. Epub 2014 Aug 21.
- Kamya MR, Kapisi J, Bigira V, Clark TD, Kinara S, Mwangwa F, Muhindo MK, Kakuru A, Aweeka FT, Huang L, Jagannathan P, Achan J, Havlir DV, Rosenthal PJ, Dorsey G. Efficacy and safety of three regimens for the prevention of malaria in young HIV-exposed Ugandan children: a randomized controlled trial. AIDS. 2014 Nov 28;28(18):2701-9. doi: 10.1097/QAD.0000000000000497.
- Kapisi J, Bigira V, Clark T, Kinara S, Mwangwa F, Achan J, Kamya M, Soremekun S, Dorsey G. Efficacy and safety of artemether-lumefantrine for the treatment of uncomplicated malaria in the setting of three different chemopreventive regimens. Malar J. 2015 Feb 5;14:53. doi: 10.1186/s12936-015-0583-9.
- Snyman K, Mwangwa F, Bigira V, Kapisi J, Clark TD, Osterbauer B, Greenhouse B, Sturrock H, Gosling R, Liu J, Dorsey G. Poor housing construction associated with increased malaria incidence in a cohort of young Ugandan children. Am J Trop Med Hyg. 2015 Jun;92(6):1207-13. doi: 10.4269/ajtmh.14-0828. Epub 2015 Apr 13.
- Bigira V, Kapisi J, Clark TD, Kinara S, Mwangwa F, Muhindo MK, Osterbauer B, Aweeka FT, Huang L, Achan J, Havlir DV, Rosenthal PJ, Kamya MR, Dorsey G. Protective efficacy and safety of three antimalarial regimens for the prevention of malaria in young Ugandan children: a randomized controlled trial. PLoS Med. 2014 Aug 5;11(8):e1001689. doi: 10.1371/journal.pmed.1001689. eCollection 2014 Aug.
- Sundell K, Jagannathan P, Huang L, Bigira V, Kapisi J, Kakuru MM, Savic R, Kamya MR, Dorsey G, Aweeka F. Variable piperaquine exposure significantly impacts protective efficacy of monthly dihydroartemisinin-piperaquine for the prevention of malaria in Ugandan children. Malar J. 2015 Sep 24;14:368. doi: 10.1186/s12936-015-0908-8.
- Tumwebaze P, Conrad MD, Walakira A, LeClair N, Byaruhanga O, Nakazibwe C, Kozak B, Bloome J, Okiring J, Kakuru A, Bigira V, Kapisi J, Legac J, Gut J, Cooper RA, Kamya MR, Havlir DV, Dorsey G, Greenhouse B, Nsobya SL, Rosenthal PJ. Impact of antimalarial treatment and chemoprevention on the drug sensitivity of malaria parasites isolated from ugandan children. Antimicrob Agents Chemother. 2015;59(6):3018-30. doi: 10.1128/AAC.05141-14. Epub 2015 Mar 9.
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Infections
- Vector Borne Diseases
- Parasitic Diseases
- Protozoan Infections
- Malaria
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Enzyme Inhibitors
- Anti-Bacterial Agents
- Cytochrome P-450 Enzyme Inhibitors
- Antiprotozoal Agents
- Antiparasitic Agents
- Antimalarials
- Folic Acid Antagonists
- Anti-Dyskinesia Agents
- Anti-Infective Agents, Urinary
- Renal Agents
- Cytochrome P-450 CYP2C8 Inhibitors
- Pyrimethamine
- Trimethoprim
- Sulfamethoxazole
- Trimethoprim, Sulfamethoxazole Drug Combination
- Piperaquine
- Sulfadoxine
- Fanasil, pyrimethamine drug combination
- Artenimol
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)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Malaria
-
University of California, San FranciscoCenters for Disease Control and Prevention; University of Massachusetts, Amherst and other collaboratorsRecruitingPlasmodium Falciparum Malaria | Plasmodium Vivax MalariaLao People's Democratic Republic
-
University of OxfordWellcome Trust; Ministry of public Health AfghanistanCompletedVivax Malaria | Uncomplicated Falciparum MalariaAfghanistan
-
Menzies School of Health ResearchInternational Centre for Diarrhoeal Disease Research, Bangladesh; Addis Ababa... and other collaboratorsCompletedMalaria | Vivax Malaria | Falciparum MalariaEthiopia, Bangladesh, Indonesia
-
Medicines for Malaria VentureAsociacion Civil Selva AmazonicaCompletedPlasmodium Falciparum Malaria | Plasmodium Vivax MalariaPeru
-
Gadjah Mada UniversityMenzies School of Health Research; Eijkman Institute for Molecular Biology; Timika...Completed
-
London School of Hygiene and Tropical MedicineWorld Health Organization; United Nations High Commissioner for Refugees; HealthNet... and other collaboratorsCompletedMalaria | Vivax Malaria | Falciparum MalariaPakistan
-
Menzies School of Health ResearchNational Health and Medical Research Council, Australia; Wellcome Trust; National...CompletedVivax Malaria | Falciparum MalariaIndonesia
-
Menzies School of Health ResearchNational Health and Medical Research Council, Australia; Wellcome Trust; National...CompletedVivax Malaria | Falciparum MalariaIndonesia
-
Research Institute for Tropical Medicine, PhilippinesWorld Health OrganizationCompletedTES of Artemether-lumefantrine for Pf and Chloroquine for Pv in the Philippines From 2013-2014 (TES)Malaria | Vivax Malaria | Falciparum Malaria | Malaria Recrudescence
-
University of IbadanShin Poong Pharm Co Ltd 161 yoksam-ro, Gangnam-Gu Seoul 135-925, Korea; Institute...CompletedPlasmodium Falciparum Malaria | Uncomplicated Malaria | Malaria FeverNigeria
Clinical Trials on trimethoprim-sulfamethoxazole (TS; TMP/SMX)
-
University of AlbertaRecruiting
-
Immtech Pharmaceuticals, IncTerminatedHIV Infections | Pneumonia, Pneumocystis Carinii | Pneumocystis Carinii Pneumonia | Pneumonia, Interstitial Plasma CellUnited States
-
Lundquist Institute for Biomedical Innovation at...National Institute of Allergy and Infectious Diseases (NIAID); Washington University... and other collaboratorsRecruitingMethicillin-resistant Staphylococcus Aureus | Skin InfectionUnited States
-
Baylor College of MedicineCompleted
-
Michael Cohen-WolkowiezEunice Kennedy Shriver National Institute of Child Health and Human Development...CompletedBacterial InfectionsUnited States
-
National Institutes of Health Clinical Center (CC)Emory University; Duke UniversityCompletedStenotrophomonas InfectionUnited States
-
University of California, San FranciscoEunice Kennedy Shriver National Institute of Child Health and Human Development...CompletedMalaria | Human Immunodeficiency VirusUganda
-
Astellas Institute for Regenerative MedicineRecruiting
-
International Maternal Pediatric Adolescent AIDS...National Institute of Allergy and Infectious Diseases (NIAID); Comprehensive... and other collaboratorsTerminatedHIV Infection | Tuberculosis | Pneumocystis Jiroveci PneumoniaBotswana, South Africa
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)WithdrawnLymphoma | Myelodysplastic Syndromes | Leukemia | Chronic Myeloproliferative Disorders | Unspecified Adult Solid Tumor, Protocol Specific | Infection | Multiple Myeloma and Plasma Cell Neoplasm | Lymphoproliferative Disorder | Myelodysplastic/Myeloproliferative Neoplasms