Impact of Artemisinin-based Combination Therapy and Quinine on Treatment Failure and Resistance in Uncomplicated Malaria

• Status: Completed
• Trial end date: 2014-06-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a bi-centric phase IIIb, randomized, open label, 3-arm clinical trial performed to investigate the impact of retreatment with an Artemisinin-Based Combination (ACT), for example Arthemeter-Lumefantrine (AL) in Uganda (Ug) and artesunate-amodiaquine (ASAQ) in RDCongo, on malaria incidence and its potential selection of resistant strains.

Patients will be followed-up for efficacy and safety during 42 days after treatment with the first line therapy recommended by the national authorities(arthemeter-lumefantrine in Uganda and artesunate-amodiaquine in RDCongo) and retreated the patients either with the same ACT or an other ACT or oral Quinine + clyndamicin.

The investigators hypothesize that (re)treatment with the first line ACT treatment beyond 14 days is as efficacious as any other rescue treatment, without the risk of selecting drug resistant strains.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Universiteit Antwerpen
• Collaborators: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA); Centre Muraz; European and Developing Countries Clinical Trials Partnership (EDCTP); Fund for Scientific Research, Flanders, Belgium; Institute of Tropical Medicine, Belgium; Makerere University; University of Kinshasa
• Treatments: Amodiaquine; Artemether; Artemether-lumefantrine combination; Artemether, Lumefantrine Drug Combination; Artemisinine; Artemisinins; Artesunate; Clindamycin; Clindamycin palmitate; Clindamycin phosphate; Lumefantrine; Quinine

Criteria

Inclusion Criteria:

1. Have been enrolled in the first phase

2. Recurrent Plasmodium falciparum infection with clinical symptoms.

3. Parents' or guardians' willingness and ability to comply with the study protocol for the duration of the study.

4. Signed (or thumb-printed whenever parents/guardians are illiterate) (second) informed consent by the parents or guardians. Note: the informed consent will cover the whole period of the study, including additional active follow ups

Exclusion Criteria:

Patients with at least one of the following criteria will be excluded:

1. Participation in any other investigational drug study (antimalarial or others) during the previous 30 days.

2. Known hypersensitivity and previous Serious Adverse Events related to the study drugsto the study drugs.

3. Severe malaria( WHO 2000) or danger signs: not able to drink or breast-feed, vomiting (> twice in 24hours), recent history of convulsions (>1 in 24h), unconscious state, unable to sit or stand.

4. Presence of intercurrent illness or any condition (cardiac, renal, hematologic, hepatic diseases) which in the judgement of the investigator would place the subject at undue risk or interfere with the results of the study, including known G6PD deficiency.

5. Patients who are taking drug which may prolong the QT (imidazole and triazole, antifungal agent).

6. Severe malnutrition (defined as weight for height <70% of the median NCHS/WHO reference).

7. Ongoing prophylaxis with drugs having antimalarial activity such as cotrimoxazole for the prevention of Pneumocisti carini pneumonia in children born to HIV+ women.