Efficacy of the antimalarial drugs recommended by the National Malaria Control Programme in Madagascar

• Register: ISRCTN
• Last refreshed on: 21 January 2020
• Main ID: ISRCTN36517335
• Date of registration: 29/05/2009
• Prospective Registration: No
• Primary sponsor: Ministry of Health (Madagascar)
• Public title: Efficacy of the antimalarial drugs recommended by the National Malaria Control Programme in Madagascar
• Scientific title: Assessment of the efficacy of antimalarial drugs recommended by the National Malaria Control Programme in Madagascar in Plasmodium falciparum and Plasmodium vivax malaria: a randomised open-label active-controlled parallel-assignment efficacy trial
• Date of first enrolment: 01/02/2006
• Target sample size: 1554
• Recruitment status: Completed
• URL: http://isrctn.com/ISRCTN36517335
• Study type: Interventional
• Study design: Randomised open-label active-controlled parallel-assignment efficacy trial (Treatment)
• Phase: Not Applicable

Countries of recruitment

Madagascar

Contacts

• Name: Didier Menard

Key inclusion & exclusion criteria

Inclusion criteria:
P. falciparum trial:
1. Both males and females, aged between six months and 15 years
2. Monoinfection with P. falciparum at a parasitaemia between 1,000 and 200,000/µl
3. Axillary temperature greater than or equal to 37.5°C
4. Body weight greater than 5 kg
5. Absence of severe malnutrition (defined as a child whose weight-for-height is below 3 standard deviations of less than 70% of the median of World Health Organization [WHO] reference values, or who has symmetrical oedema involving at least the feet)
6. Absence of febrile conditions caused by diseases other than malaria
7. Absence of 'danger signs' (inability to stand, breastfeeding or drink; recent convulsions; lethargy or persistent vomiting) and of severe and complicated malaria
8. Haemoglobin (Hb) greater than or equal to 5 g/dl
9. Informed written consent of parents/guardians
10. Ability to attend stipulated follow-up visits
11. Absence of history of hypersensitivity reactions to any of the drugs being evaluated

P. vivax trial:
1. Both males and females, aged greater than 6 months
2. Monoinfection with P. vvax at a parasitaemia above 250/µl
3. History of fever during 48 hours prior to time of recruitment
4. Ability and willingness to participate based on information given to parent or guardian and access to health facility
5. Informed consent

Exclusion criteria:
P. falciparum trial:
1. Aged less than 6 or greater than 16 years
2. Severe malnutrition (defined as a child whose weight-for-height is below 3 standard deviations of less than 70% of the median of WHO reference values, or who has symmetrical oedema involving at least the feet)
3. No slide confirmed infection with P. falciparum or a mixed infection that includes a non P. falciparum species
4. Initial parasite density less than 1,000 or greater than 200,000 asexual parasites per microlitre
5. Presence of general danger signs among children less than 5 years (inability to stand, breastfeeding or drink; recent convulsions; lethargy or persistent vomiting) and of severe and complicated malaria
6. Measured axillary temperature less than 37.5 °C
7. Inability to attend stipulated follow-up visits
8. Unwilling to provide informed consent provided by parent/guardian
9. History of hypersensitivity reactions to any of the drugs being evaluated

P. vivax trial
1. Presence of clinical condition requiring hospitalisation
2. Presence of severe malnutrition
3. Pregnancy
4. Significant concomitant febrile illness which would interfere with follow-up
5. Chronic infectious diseases other than malaria (e.g., tuberculosis)
6. Known allergy and/or intolerance to drug(s) being tested


Age minimum:
Age maximum:
Gender: Both

Health Condition(s) or Problem(s) studied

Malaria (P. falciparum and P. vivax)
Infections and Infestations
Plasmodium falciparum malaria

Intervention(s)

P. falciparum clinical trial:
All patients aged between 6 months and 15 years were eligible to be enrolled and were screened for malaria at the primary health centres in the sentinel sites on the basis of history of febrile illness. Once written informed consent was given, patients were enrolled in the study and assigned consecutive patient numbers.

Randomisation to treatment group was performed in blocks of three or four, and treatment regimens were allocated by an independent individual, not involved in the analysis of the study. Patients were administered either CQ (10 mg/kg on days 0 and 1, and 5 mg/kg on day 2), AQ (10 mg/kg on days 0, 1, and 2), SP (25 mg/kg sulphadoxine and 1.25 mg/kg pyrimethamine as a single dose on day 0) or ASAQ (AS: 4 mg/kg on days 0, 1, and 2 and AQ:10 mg/kg on days 0, 1, and 2). Patients were directly observed for 30 minutes after treatment, and the dose was readministered if vomiting occurred. Patients who repeatedly vomited their first dose of study medication were excluded from the study. Patients were assessed on days 1, 2, 3, 7, 14, 21 and 28, and any intervening day they were unwell for malaria infection. Blood was obtained by finger prick on all follow-up days and on any unscheduled day to use for analysis of thick and thin blood smears and for storage on filter paper. Thick and thin blood slides were examined by light microscopy for parasites on any day during the 28-day follow-up. Blood slides were read by a microscopist blind to treatment allocation. All slides were controlled by a second microscopist also blind to treatment group and previous diagnosis. Discordant slides were read, blind to treatment group and previous diagnosis, by a third microscopist. Haemoglobin was measured

Primary Outcome(s)

P. falciparum:
Treatment outcomes were assessed according to WHO 2003 guidelines as Early Treatment Failure (ETF; danger signs or complicated malaria or failure to adequately respond to therapy on days 0 - 3), Late Clinical Failure (LCF; danger signs or complicated malaria or fever and parasitaemia on days 4 - 28 without previously meeting criteria for ETF), Late Parasitological Failure (LPF; asymptomatic parasitaemia on days 4 - 28 without previously meeting criteria for ETF or LCF), and Adequate Clinical and Parasitological Response (ACPR; absence of parasitaemia on day 28 without previously meeting criteria for ETF, LCF, or LPF). Overall Treatment failure (OFT) was considered as the sum of the ETP, LCT and LPF. Patients classified as having suffered treatment failure were treated with quinine (10 mg/kg three times daily for seven days); however, their response to repeat therapy was not assessed.

P. vivax:
Treatment outcomes were assessed according to WHO 2001 guidelines as "treatment failure" (TF; clinical deterioration due to P. vivax illness requiring hospitalisation, with parasitaemia and an axillary temperature of greater than or equal to 37.5°C any time between days 3 and 28, or parasitaemia on any day between days 7 and 28, regardless of clinical condition) or "adequate clinical and parasitological response" (ACPR; absence of parasitaemia on day 28 without the criteria for TF having been met previously). Patients with TF were treated with artesunate (4 mg/kg on days 0, 1, and 2) plus amodiaquine (10 mg/kg on days 0, 1, and 2), but their response to rescue therapy was not assessed.

Secondary Outcome(s)

No secondary outcome measures

Secondary ID(s)

MDG-304-G05-M

Source(s) of Monetary Support

The Global Fund to Fight AIDS, Tuberculosis and Malaria (Switzerland) - Round three grant (ref: MDG-304-G05-M)

Ethics review

Status:
Approval date:
Contact:

National Ethics Committee of the Ministry of Health of Madagascar approved in February 2006 (ref: 007/SANPF/2007)

Results

• Results available: Yes
• Date Completed: 31/07/2007