Evaluating the Role of Chloroquine for Malaria Elimination
Keywords
Abstract
Description
This surveillance study is a two-arm prospective evaluation of parasitological responses to directly observed treatment with CQ (vs. placebo) for the clearing of asymptomatic parasitemia. People with asymptomatic P. falciparum parasitaemia, defined as the presence of a P. falciparum infection in the absence of any clinical symptomatology including fever, history of fever in the preceding 24 hours, malaise, fatigue, chills, or any other symptoms that may be derived from the malarial infection, who meet the study inclusion criteria will be enrolled, treated on site with CQ phosphate (25mg/Kg CQ base divided in three daily doses: 10mg/kg day 1 (usually 4 tablets); 10mg/kg day 2 (4 tablets) and 5mg/kg day 3 (2 tablets)) or placebo pills (same schedule, 4 tablets day one and two; and 2 tablets on day three), and monitored for 28 days. The follow-up will consist 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 will be classified as having therapeutic failure (early or late) or an adequate response. The proportion of patients experiencing therapeutic failure during the follow-up period will be used to estimate the efficacy of the study drug. PCR analysis will be used to distinguish between a true recrudescence due to treatment failure and episodes of reinfection.
Dates
| Last Verified: | 01/31/2016 |
| First Submitted: | 01/12/2015 |
| Estimated Enrollment Submitted: | 02/28/2016 |
| First Posted: | 03/03/2016 |
| Last Update Submitted: | 02/05/2018 |
| Last Update Posted: | 02/06/2018 |
| Actual Study Start Date: | 12/31/2014 |
| Estimated Primary Completion Date: | 03/31/2015 |
| Estimated Study Completion Date: | 05/31/2015 |
Condition or disease
Intervention/treatment
Drug: Chloroquine
Drug: Placebo
Phase
Arm Groups
| 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). | Drug: 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). |
| 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. | Drug: Placebo 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 |
Eligibility Criteria
| Ages Eligible for Study | 18 Years To 18 Years |
| Sexes Eligible for Study | Male |
| Accepts Healthy Volunteers | Yes |
| Criteria | 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 |
Outcome
Primary Outcome Measures
1. Adequate parasitologic response (APR) to therapy [28 days after first day of drug intake]
Secondary Outcome Measures
1. Early parasitologic failure [1-3 days after first day of drug intake]
2. Late parasitologic failure [4-28 days after first day of drug intake]
3. Prevalence of chloroquine conferring pfcrt K76T mutation in pre-treatment infections [0 days after first day of drug intake]
4. Rates of pre treatment pfcrt K76T mutation in cases of chloroquine treatment failure [0 days after first day of drug intake]
5. Rates of post treatment pfcrt K76T mutation in cases of chloroquine treatment failure [28 days after first day of drug intake]
6. Clearance time of parasitaemia [28 days after first day of drug intake]
