- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02698748
Evaluating the Role of Chloroquine for Malaria Elimination (Cloroquina)
Evaluating the Potential Role of Chloroquine in Preventing Infections During Elimination Campaigns: A Randomized, Single-blind, Placebo-controlled Trial in Asymptomatic Mozambican Adults
One of the proposed ideas for malaria elimination includes the use of drugs to interrupt malaria transmission by exhausting the human reservoir of infection. Theoretically, mass treatment of an entire population with a very effective and rapid-acting drug (for instance an ACT), followed by the administration of an effective prophylactic regime during a minimum of four weeks, so as to outlast the typical development period of Plasmodium parasites in Anopheline mosquitoes, could achieve the same objective. In this respect, chloroquine (CQ) would be an appropriate candidate. This drug exhibits two conditions that make it attractive for elimination campaigns: 1) It has been demonstrated to have an excellent safety profile, allowing for its use in all age groups including pregnant women and children; and 2) Its relatively long elimination half life (t1/2=1-2 months) can provide a long post-treatment prophylactic effect. Recent evidence suggests that CQ sensitivity may be returning in places where discontinuation has reduced the drug pressure to the parasite populations. In countries such as Malawi, P. falciparum seems to have regained full sensitivity to CQ, and molecular markers of antiCQ resistance have nearly disappeared. While this does not support the reintroduction of CQ as first line therapy, it does suggest that, if proven sensitive in a given area, it could play a prophylactic role in malaria elimination strategies when used in combination with other drugs or tools. Thus, we intend to evaluate the potential role of chloroquine in preventing infections during elimination campaigns by performing a randomized, single-blind, placebo-controlled trial in asymptomatic Mozambican adults.
Choosing asymptomatic parasitaemic adult males from a malaria-endemic area as our study population introduces limited risks when administering a drug with an uncertain efficacy (47% efficacious in 2001-2002). In malaria-endemic areas, this age group has a remarkably low risk of developing severe disease (irrespective of clinical symptoms), and it is foreseeable that parasitemia may be well tolerated, and in certain cases, spontaneously cleared from the individual's blood as a result of the immune system. In the unlikely event of any clinical symptomatology appearing throughout the follow-up, individuals will be examined by a study clinician and treated immediately with the country's first-line malaria treatment (artemether-lumefantrine, Coartem ®).
Study Overview
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 3
Contacts and Locations
Study Locations
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Maputo
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Manhiça, Maputo, Mozambique, 1902
- Centro de Investigaçao em Saúde de Manhiça
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Male individuals
- P. falciparum infection detected by microscopy (Minimum 250 parasites/microliter; Maximum 10.000parasites/microliter)
- Ability to swallow oral medication
- Ability and willingness to comply with the study protocol for the duration of the study and to comply with the study visit schedule; and
- Informed consent from the participant individual
Exclusion Criteria:
- Age <18 years
- Female individuals
- Axillary temperature >=37.5ºC
- Presence of any other co-existing clinical condition that in the opinion of the recruiting physician would not allow the individual to be considered a "healthy" asymptomatic carrier
- Regular medication which may interfere with antimalarial efficacy or antimalarial pharmacokinetics, such as Cotrimoxazole
- History of hypersensitivity reactions or contraindications to CQ
- Known HIV positive patients in treatment with antiretrovirals
Study Plan
How is the study designed?
Design Details
- Primary Purpose: PREVENTION
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: SINGLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Chloroquine
Chloroquine sulphate (Meriquine®; 250mg; 150 mg of chloroquine base; Baroda, India) will be administered at a total dose of 25 mg/kg (expressed as mg of CQ base per kg body weight, once daily during 3 consecutive days, following the schedule 10mg/kg Day 1; 10mg/kg day 2 and 5 mg/kg day 3).
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Chloroquine sulphate (Meriquine®; 250mg; 150 mg of chloroquine base; Baroda, India) will be administered at a total dose of 25 mg/kg (expressed as mg of CQ base per kg body weight, once daily during 3 consecutive days, following the schedule 10mg/kg Day 1; 10mg/kg day 2 and 5 mg/kg day 3).
Other Names:
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PLACEBO_COMPARATOR: Placebo
Placebo pills will be standard placebo capsules filled with powder contents with no pharmaceutical activity.
They will not be identical to the chloroquine tablets, so the study will not be double blind, but rather single blinded.
Placebo tablets will be manufactured by the pharmaceutical department of the Hospital Clínic, in Barcelona, Spain.
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Placebo Placebo pills will be standard placebo capsules filled with powder contents with no pharmaceutical activity.
They will not be identical to the chloroquine tablets, so the study will not be double blind, but rather single blinded.
Placebo tablets will be manufactured by the pharmaceutical department of the Hospital Clínic, in Barcelona, Spain
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Adequate parasitologic response (APR) to therapy
Time Frame: 28 days after first day of drug intake
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the absence of parasitemia at the end of the trial's follow-up period (Day 28), regardless of axillary temperature, without having previously met any of the criteria for early and late treatment failure
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28 days after first day of drug intake
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Early parasitologic failure
Time Frame: 1-3 days after first day of drug intake
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Detection of parasites once the initial parasitemia has been cleared in the time period from day 1 to day 3 after first day of drug intake
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1-3 days after first day of drug intake
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Late parasitologic failure
Time Frame: 4-28 days after first day of drug intake
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The detection of parasites in patients having cleared their initial parasitemia anytime from day 4 to day 28
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4-28 days after first day of drug intake
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Prevalence of chloroquine conferring pfcrt K76T mutation in pre-treatment infections
Time Frame: 0 days after first day of drug intake
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Proportion of the isolates detected with this specific mutation among isolates at baseline (before study drug initiation)
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0 days after first day of drug intake
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Rates of pre treatment pfcrt K76T mutation in cases of chloroquine treatment failure
Time Frame: 0 days after first day of drug intake
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Proportion of the isolates detected with this specific mutation at baseline among cases with confirmed treatment failure those
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0 days after first day of drug intake
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Rates of post treatment pfcrt K76T mutation in cases of chloroquine treatment failure
Time Frame: 28 days after first day of drug intake
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Proportion of the isolates detected as new infections or recrudescent ones with this specific mutation
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28 days after first day of drug intake
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Clearance time of parasitaemia
Time Frame: 28 days after first day of drug intake
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time in hours until the clearance of parasitemia
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28 days after first day of drug intake
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Collaborators and Investigators
Investigators
- Principal Investigator: Pedro Aide, MD, MSc, PhD, Centro de Investigaçao em Saúde de Manhiça
Publications and helpful links
General Publications
- Galatas B, Marti-Soler H, Nhamussua L, Cistero P, Aide P, Saute F, Menendez C, Rabinovich NR, Alonso PL, Bassat Q, Mayor A. Dynamics of Afebrile Plasmodium falciparum Infections in Mozambican Men. Clin Infect Dis. 2018 Sep 14;67(7):1045-1052. doi: 10.1093/cid/ciy219.
- Galatas B, Nhamussua L, Candrinho B, Mabote L, Cistero P, Gupta H, Rabinovich R, Menendez C, Macete E, Saute F, Mayor A, Alonso P, Bassat Q, Aide P. In-Vivo Efficacy of Chloroquine to Clear Asymptomatic Infections in Mozambican Adults: A Randomized, Placebo-controlled Trial with Implications for Elimination Strategies. Sci Rep. 2017 May 2;7(1):1356. doi: 10.1038/s41598-017-01365-4.
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Infections
- Vector Borne Diseases
- Parasitic Diseases
- Protozoan Infections
- Malaria
- Physiological Effects of Drugs
- Anti-Infective Agents
- Peripheral Nervous System Agents
- Analgesics
- Sensory System Agents
- Anti-Inflammatory Agents, Non-Steroidal
- Analgesics, Non-Narcotic
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Antiprotozoal Agents
- Antiparasitic Agents
- Antimalarials
- Amebicides
- Filaricides
- Antinematodal Agents
- Anthelmintics
- Chloroquine
- Chloroquine diphosphate
Other Study ID Numbers
- CNBS (173/CNBS/13)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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