Clinical Trials Logo

Clinical Trial Summary

The general objective of this study is to assess the therapeutic efficacy and safety of artesunate + amodiaquine combined with a single low dose of primaquine (0.25 mg/kg) for the treatment of uncomplicated P. falciparum malaria patients in Zanzibar.

The specific objectives are:

- To determine the clinical and parasitological efficacy of artesunate + amodiaquine and primaquine in the treatment of uncomplicated Plasmodium falciparum infection.

- To differentiate recurrent infections during follow-up, i.e. recrudescence from new infections, by polymerase chain reaction (PCR).

- To evaluate the incidence of adverse events, particularly with regards to potential hematological adverse events of primaquine.

- To determine the polymorphism of molecular markers associated with artesunate + amodiaquine tolerance/resistance.

- To formulate recommendations, which will enable the Zanzibar Ministry of Health to make informed decisions about whether the current national antimalarial treatment guidelines should be updated or not.

- To determine efficacy rate of the first line treatment compared to the first efficacy trial thirteen years ago.


Clinical Trial Description

The aim of this study is to provide policymakers with updated efficacy and safety data of artesunate + amodiaquine in combination with a single low dose of primaquine (0.25 mg/kg) and data on genetic markers of tolerance/resistance to artemisinin based combination therapies (ACTs), proposed as an early warning system for development and spread of antimalarial drug resistance, in Zanzibar. The study protocol is based on the new WHO guidelines for surveillance of antimalarial drug efficacy (WHO 2014).

This surveillance study was designed as a one-arm prospective evaluation of the clinical and parasitological responses to directly observed treatment for uncomplicated malaria. Participants were recruited from febrile patients, i.e. documented axillary temperature ≥37.5 °C or history of fever during the past 48 hours, of 3 months and older, presenting at primary health care facilities in Zanzibar, with microscopy confirmed uncomplicated P. falciparum infection. Enrolled patients received directly observed treatment with artesunate + amodiaquine once daily for 3 consecutive days according to the national malaria treatment guidelines. A single low dose of primaquine (0.25 mg/kg) was administered together with the first artesunate + amodiaquine dose. Clinical and parasitological as well as safety parameters were monitored over a 28-day follow-up period. The follow-up consisted of a fixed schedule of check-up visits and corresponding clinical and laboratory examinations. On the basis of the results of these assessments, the patients were classified as having therapeutic failure (early or late) or an adequate response. Blood samples from patients experiencing therapeutic failure during the follow-up period were used to estimate the efficacy of the study drugs based on PCR analysis to distinguish between recrudescence (treatment failures) and reinfection (new infections).

A standard physical examination was performed at baseline (day 0 before drug administration) and on days 1, 2, 3, 7, 14, 21, and 28 ,or any other day if the patient returned spontaneously and parasitological reassessment was required. This examination included measuring axillary temperature, with a thermometer that has a precision of 0.1 °C, as well as conducting a thick film for asexual and gametocyte counts and species identification. Haemoglobin was assessed systematically on all participants on days 0, 3, 7, 14 and 28 using Hemocue, and at any time in case of clinical suspicion of anaemia, i.e. pallor, according to standard case management of malaria in Zanzibar.

In order to differentiate a recrudescence (treatment failure/same parasite strain) from a newly acquired infection (reinfection/different parasite strain) among recurrent parasitemias found during follow-up, a genotype analysis was to be conducted. This analysis was based on the extensive diversity in the following P. falciparum genes: the merozoite surface protein 1 (msp1) and 2 (msp2), and the glutamine-rich protein (glurp) (WHO 2008). The genotypic profiles of pre- and post-parasite strains were to be compared in a stepwise manner to distinguish recrudescence from reinfection. In order to minimize discomfort to the patient due to repeated finger pricks, two to three drops of blood will be collected on a 3MM (Whatman) filter paper during screening or enrollment and each time blood smears are required according to the protocol from day 7.

The results of this study will be used to assist the Zanzibar Ministry of Health in assessing the current national treatment guidelines for uncomplicated P. falciparum malaria. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT03773536
Study type Interventional
Source Karolinska Institutet
Contact
Status Completed
Phase Phase 4
Start date May 9, 2017
Completion date September 25, 2017

See also
  Status Clinical Trial Phase
Completed NCT04577066 - Safety and Preliminary Protective Efficacy of Genetically Attenuated GA2 Parasites. Phase 1/Phase 2
Completed NCT01883609 - A Safety and Efficacy Study of ChAd63/MVA METRAP + RTS,S Phase 1/Phase 2
Completed NCT00593398 - Malarial Immunity in Pregnant Cameroonian Women
Completed NCT01659281 - Efficacy of Artesunate-Mefloquine Combination Therapy in Trat Province, Thailand N/A
Completed NCT00074841 - Trial of Azithromycin Plus Chloroquine Versus Sulfadoxine-Pyrimethamine Plus Chloroquine for the Treatment of Uncomplicated Malaria in India Phase 2/Phase 3
Recruiting NCT04416945 - Targeting High Risk Populations With Enhanced Reactive Case Detection in Southern Lao Peoples Democratic Republic N/A
Completed NCT00314899 - Fetal Immunity to Falciparum Malaria
Completed NCT02867059 - SJ733 Induced Blood Stage Malaria Challenge Study Phase 1
Completed NCT00701961 - Pharmacokinetic of Mefloquine-Artesunate in Plasmodium Falciparum Malaria Infection in Pregnancy Phase 2/Phase 3
Completed NCT00338520 - Hyperphenylalaninemia in Cerebral Malaria N/A
Completed NCT00707200 - The Cytoadherence in Pediatric Malaria (CPM) Study N/A
Completed NCT00393757 - Malaria Transmission and Immunity in Highland Kenya
Completed NCT03783299 - Targeted Active Case Detection Among High Risk Populations in Southern Lao Peoples Democratic Republic Phase 4
Completed NCT02614404 - Effect of Imatinib on Suppression of Malaria Parasites in Patients With Uncomplicated Plasmodium Falciparum Malaria Phase 1
Completed NCT00358332 - Phase I Pediatric FMP2.1/AS02A Trial in Mali Phase 1
Completed NCT00730782 - Assessment of Three Formulations of the Candidate Vaccine AMA 1 in Healthy Dutch Adult Volunteers Phase 1
Completed NCT00349713 - FMP2.1 Trial in Bandiagara, Mali Phase 1
Recruiting NCT05052502 - Targeting High Risk Populations With Enhanced Reactive Focal Mass Drug Administration in Thailand N/A
Completed NCT04093765 - Mass Screening and Treatment for Reduction of Falciparum Malaria N/A
Completed NCT03764527 - Tolerability and Efficacy of Artemether-Lumefantrine Versus Artesunate + Amodiaquine in Zanzibar Phase 4