Antimalaria Drugs Susceptibility Testing for an Effective Management of Infected Patients in Sub-Sahara Africa

NCT02974348 | Completed Phase 3 DMC

• 1 other identifier: CASTEP
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 1

Brief Summary

The antimalarial drugs efficacy and safety study will be conducted in the Clinics and hospital of the Cameroon Development Corporation (CDC) Estates, Tiko Health District, located in a typical forest and rainfall area in the South West Region Cameroon. In this study, 350 children aged 6 months to 5 years who are found to have uncomplicated symptomatic malaria will be enrolled between October 2012 and March 2013. Participants will be randomized to receive one of the following medications. (i) DHA+PQ : dihydroartemisinin, 2.5 mg per kg, plus piperaquine phosphate, 20mg per kg daily for 3 days; (ii) ART LUM : Artemether, 2mg per kg, plus lumefantrine 10mg, twice daily for 3 days; (iii) AS+MQ: artesunate, 4 mg/kg/day, with mefloquine, 8 mg/kg/day orally once a day for 3 days. All study medications will be administered orally The Primary objective of this study are to compare the efficacy, safety and tolerability of orally administered artemether plus lumefantrine (ART+LUM), artesunate plus mefloquine (AS+MQ) and dihydroartemisinin plus piperaquine (DHA+PQ) combinations in the treatment of uncomplicated falciparum malaria in Cameroon in order to provide evidence that can be used to determining the optimum antimalaria treatment policy in Cameroon. The secondary objectives are as follows (i) To valuate the efficacy and safety of artemether plus lumefantrine (ART + LUM) and artesunate plus mefloquine (AS + MQ) versus dihydroartemisinin plus piperaquine (DHA + PQ) combination (ii) To compare the clearance of asexual parasites and gametocytes in each treatment arm (iii) To assess the clearance of fever (iv) Assess effect of each treatment arm on anemia This study is a randomized, double blinded clinical trial. After enrollment, participant will be randomized to one of the three treatment regimen. The treatment outcome will be assessed through a 42-day efficacy study. Participants who will exhibit early or late treatment failure and those with adequate clinical response and parasitological failure on day 14, 28 or 42 will be treated with quinine (25mg base per kg body weight per day in three divided doses for five days). In addition to antimalarial drugs oral paracetamol (50mg/kg body weight per day in three divided doses) will be administered for fever exceeding 37.5%. Polymerase Chain Reaction (PCR) -corrected 28 day and 42 day efficacy will be evaluated for each treatment episode.

Conditions

Drug Resistant Malaria Due to Plasmodium Falciparum

Outcome Measures

Primary Outcomes (1)

• efficacy and safety assessment

  The primary endpoint was the 28-day and 42-day cure rates and was defined as proportion of patients with adequate clinical and parasitological response (ACPR) after 28 and 42 days of follow-up. Absence of parasitemia until day 28 and day 42 irrespective of axillary temperature was categorized as an adequate clinical and parasitologic response (ACPR). Secondary endpoints were early treatment failure (ETF), late clinical failure (LCF), late parasitological failure (LPF), adverse events (clinical and laboratory abnormalities), anaemia (Hematocrit \< 30%), clearance rate of fever and parasitaemia, and gametocyte

  42 days

Secondary Outcomes (3)

• Hemoglobin level

  42 days follow-up

• parasite clearance rate assessment

  42 days

• PCR-correction

  42 days

Study Arms (6)

arm 1: Arthemeter-lumefantrine

ACTIVE COMPARATOR

Arthemeter-lumefantrine (ART-LUM) is an antimalaria drug manufactured as fixed combination tablets, each containing 20 mg of artemether and 120 mg of lumefantrine. ART-LUM was administrated according to body weight as six consecutive doses: The first dose at diagnosis and the second dose eight hours later, 0- 24-48 hours

Drug: Arthemeter-lumefantrine

arm 2 : Artesunate mefloquine

ACTIVE COMPARATOR

Artesunate mefloquine (ASMQ) is an antimalaria drug administered as a combination of artesunate, 4 mg/kg/day, with mefloquine, 8 mg/kg/day orally once a day for 3 days or three times, at an interval of 24 hours (0 h - 24 h - 48 h).

Drug: Artesunate mefloquine

arm 3 : Dihydroartemisinin piperaquine

ACTIVE COMPARATOR

Dihydroartemisinin piperaquine (DHA-PQ ) is an antimalaria drug administered as a combination of dihydroartemisinin, 2.5 mg per kg, with piperaquine phosphate, 20mg per kg daily for 3 days or three times, at an interval of 24 hours

Drug: Dihydroartemisinin piperaquine

Paracetamol

OTHER

Oral paracetamol is administered at of 50mg/kg body weight per day in three divided doses for fever exceeding 37.5oC.

Drug: Paracetamol

Amoxicillin

OTHER

amoxicillin is an antibiotic administered at 50mg per kg body weight per day for seven days in the event of concomitant bacterial infection, absent on day 0 but present during the follow up.

Drug: Amoxicillin

Quinine

OTHER

Quinine is an antimalarial recommended by the WHO and NMCP to be used as second line treatment for malaria. In this study, for cases of treatment failure with the artemisinin based combination therapies, quinine sulphate is administered as a second line or rescue drug at a dose of 25mg base per kg body weight per day in three divided doses for five days. The participant is then classified as ETF or LTF and excluded from the study.

Drug: Quinine

Interventions

Arthemeter-lumefantrine DRUG

Randomization codes were computer-generated by an offsite investigator and provided to a study nurse responsible for treatment allocation. All other study personnel were blinded to the treatment assignments, and patients were not informed of their treatment regimen. Participants from Group 1: AL, Group 2 : DHAP, Group3 : ASMQ were also given appointment card for days 1, 2, 3, 7, 14, 21, 28, 35 and 42 for clinical examination and blood smears. Blood was taken on filter paper on each of these visits.

Also known as: Cofantrine®

arm 1: Arthemeter-lumefantrine

Artesunate mefloquine DRUG

Artequin® is an antimalarial drug presented as infant co-formulation of two separate drugs

Also known as: Artequin®

arm 2 : Artesunate mefloquine

Dihydroartemisinin piperaquine DRUG

Malacur®. is an antimalarial drug presentad as co-formulation of two separate drugs

Also known as: Malacur®

arm 3 : Dihydroartemisinin piperaquine

Paracetamol DRUG

Paracetamol, is an antipyretic drug, presented as tablets or syrup in infants formulation

Also known as: Paracetamol syrup

Paracetamol

Amoxicillin DRUG

Amoxicillin is an antibiotic with no reported activity on plasmodium

Also known as: Clamoxyl® 125 mg/5mL

Amoxicillin

Quinine DRUG

quinine sulphate is an antimalaria drug administered as a second line or rescue drug

Also known as: Quinine sulphate

Quinine

Eligibility Criteria

• Age: 6 Months - 59 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• signs/symptoms of uncomplicated malaria with axillary temperature ≥ 37.5;
• monoinfection with Plasmodium falciparum;
• parasite count between 2000 and 200 000 per μl;
• haemoglobin level\> 5 g/dL;
• absence of signs/symptoms of severe malaria or other diseases requiring drugs with antimalaria or antihistaminic activities;
• parent/guardian willingness to give their consent

You may not qualify if:

• Chronic disease (HIV, malnutrition etc.),
• severe anaemia (haemoglobin level\< 5 g/dL),
• respiratory distress, inability to drink, convulsion etc.,
• history of intolerance to test drugs;
• co-infection requiring drug with antihistaminic or antimalaria activities such as cotrimozaxole

Sponsors & Collaborators

• University of Bamenda: lead
• Ministry of Science and Technology of the People´s Republic of China: collaborator
• National Institute for Parasitic Disease, Chinese Center for Disease Control and Prevention: collaborator

Study Sites (1)

CDC Hospital

Tiko, South-West Region, 237, Cameroon

Location

Related Publications (24)

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  PMID: 32188442 DERIVED

MeSH Terms

Interventions

Acetaminophen; Amoxicillin; Quinine

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Ampicillin; Penicillin G; Penicillins; beta-Lactams; Lactams; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Cinchona Alkaloids; Alkaloids; Quinuclidines; Heterocyclic Compounds, Bridged-Ring; Quinolines

Study Officials

• Xiaonong Zhou, PhD

  National Institute for Parasitic Disease

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 18, 2016
• First Posted: November 28, 2016
• Study Start: January 1, 2013
• Primary Completion: May 1, 2013
• Study Completion: October 1, 2014
• Last Updated: November 29, 2016

Record last verified: 2016-11

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)