Clinical trial NCT01150344: Evaluation of the Riamet® Versus Malarone® in the Treatment of Uncomplicated Malaria
Official title: Effectiveness and Safety Evaluation of the Riamet® Versus Malarone® in the Treatment of Uncomplicated Malaria : a Multicentric Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Malaria
Keywords: Multicentric study
Antimalarial
P. falciparum
Efficacy
Failures
Malarone
RIAMET
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2010-06-24
Enrollment: 317
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Riamet® or Malarone® are both recommended as the first line treatment for uncomplicated malaria in France, according to the French consensus Conference revised in 2007 on the treatment of imported malaria.

The aim of the study is to compare both tolerance and efficacy of Malarone® and Riamet® in the treatment of uncomplicated imported malaria and to determine clinical and parasitological predictive factors associated with a less effectiveness. It's a multicentric, randomised study in adults with uncomplicated malaria. Treatment will be administered for 3 days, and patients will be followed for 28 days, to evaluate the therapeutic evolution. 640 patients will be included among 15 centres.

Detailed description: Background : RIAMET® or Malarone® are both recommended as the first line treatment for uncomplicated malaria in France, according to the French consensus Conference revised in 2007 on the treatment of imported malaria. Today no randomized controlled trial (RCT) comparing both treatments are available for either tolerance or efficacy especially in the field of imported malaria.

Malarone®, an atovaquone+proguanil combination, has become these last years the most prescribed treatment in adult in this indication in France. With Malarone®, therapeutic failures are rare, but digestive side effects are observed, such as vomiting, possibly leading to the use of a second line treatment.

Riamet®, an artemether+lumefantrine combination, is available in France since only July 2007, but is largely used in endemic areas (as CO-ARTEM). A good tolerance and efficacy are reported by studies performed in endemic areas.

Both antimalarials are to be taken for a 3-days treatment period, once a day for Malarone®, but twice a day for Riamet®, which is supposed to affect the observance, on the one hand. On the other hand, parasitological cure rate and apyrexia occur faster with RIAMETt® than with Malarone®.

Primary objective: to compare both tolerance et efficacy of Malarone® and RIAMET® in the treatment of uncomplicated imported malaria.

Secondary objective: to determine clinical and parasitological predictive factors associated with a less effectiveness.

Primary outcome: Number of cases where a second line treatment is used for either intolerance or lack of effectiveness within the 28 days after diagnosis of malaria.

Secondary outcome: parasitological cure rate at J3, fever clearance, digestive tolerance, number of relapses.

Design: Multicentric, open-label, randomized, controlled trial of superiority in adults with uncomplicated malaria and no contraindications to the oral treatment. Treatment will be administered for 3 days, and patients will be followed for 28 days, according to the national recommendations, to evaluate the therapeutic evolution. 640 patients will be included within 36 months. Recruitment will take place among 15 of the corresponding centres of the Malaria National Reference Centre.

Inclusion criteria : subjects aged more than 18, back from an endemic area with a positive diagnosis of Plasmodium falciparum by microscopic blood (thin and thick film) examination, able to come back at J3, J7 and J28, consent to participate.

Non inclusion criteria: pregnancy, ECG abnormality, contraindication to treatment, previous anti-malaric treatment within 30 days (HALOFANTRIN) or 48 hours (other antimalarial treatments).

Sample size justification: considering that 13% of patients on Malarone® will be treated by a second line of treatment, 300 patients per group would be necessary to achieve a relative reduction of 50% of patients treated by a second line of treatment (i.e. 6,5%) in the RIAMET® group, with a 80% of statistical power and a type I error rate taken to be 0,05. Considering 5% of patients lost of follow up, 640 patients have to be included.

Perspectives : these data should help to define the best 1st line of treatment in the uncomplicated malaria.

Eligibility criteria: Inclusion Criteria:

* subjects aged more than 18,
* back from an endemic area with a positive diagnosis of Plasmodium falciparum by microscopic blood (thin and thick film) examination,
* absence of any severe manifestation according to the WHO definition of severe falciparum malaria

EXCLUSION CRITERIA:

* pregnancy,
* ECG abnormality,
* contraindication to treatment,
* previous anti-malaric treatment within 30 days,
* unable to come back at J3, J7 and J28,
* unwilling to consent to participate

Primary outcomes:
measure: Number of cases where a second line treatment is used for either intolerance or lack of effectiveness
timeFrame: within the 28 days after diagnosis of malaria
Secondary outcomes:
measure: Parasitological cure rate
timeFrame: At day 3
measure: Fever clearance
timeFrame: At day 3
measure: Digestive tolerance
timeFrame: At day 3
measure: Number of relapses
timeFrame: At day 3
Other outcomes:
Locations:
city: Bobigny
country: France
facility: Hôpital Avicenne
state: Seine St Denis
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Olivier Bouchaud, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: