Evaluating the Role of Chloroquine for Malaria Elimination

NCT ID: NCT02698748

Last Updated: 2018-02-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 75 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-01-31
• Study Completion Date: 2015-06-30

Brief Summary

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 ®).

Detailed 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.

Conditions

Malaria

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: SINGLE

Study Groups

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).

Group Type: EXPERIMENTAL

Chloroquine

Intervention Type: DRUG

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

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Interventions

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).

Intervention Type: 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

Intervention Type: DRUG

Other Intervention Names

Chloroquine Phosphate; Placebo capsules

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Centro de Investigacao em Saude de Manhica

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Pedro Aide, MD, MSc, PhD

Role: PRINCIPAL_INVESTIGATOR

Centro de Investigação em Saude de Manhiça

Locations

Centro de Investigaçao em Saude de Manhiça

Manhiça, Maputo Province, Mozambique

Countries

Mozambique

References

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.

Reference Type: DERIVED

PMID: 29546346 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 28465550 (View on PubMed)

Other Identifiers

CNBS (173/CNBS/13)

Identifier Type: -

Identifier Source: org_study_id