Evaluating the Role of Chloroquine for Malaria Elimination

Malaria Clinical Trial

— Cloroquina  

Official title:

Evaluating the Potential Role of Chloroquine in Preventing Infections During Elimination Campaigns: A Randomized, Single-blind, Placebo-controlled Trial in Asymptomatic Mozambican Adults

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02698748
• Other study ID #: CNBS (173/CNBS/13)
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: January 13, 2015
• Last updated: February 6, 2018
• Start date: January 2015
• Est. completion date: June 2015

Study information

• Verified date: February 2016
• Source: Centro de Investigacao em Saude de Manhica
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 ®).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 75
• Est. completion date: June 2015
• Est. primary completion date: April 2015
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Malaria

Intervention

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
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

Locations

Country	Name	City	State
Mozambique	Centro de Investigaçao em Saude de Manhiça	Manhiça	Maputo

Sponsors (1)

Lead Sponsor	Collaborator
Centro de Investigacao em Saude de Manhica

Country where clinical trial is conducted

Mozambique, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adequate parasitologic response (APR) to therapy	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	28 days after first day of drug intake
Secondary	Early parasitologic failure	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	1-3 days after first day of drug intake
Secondary	Late parasitologic failure	The detection of parasites in patients having cleared their initial parasitemia anytime from day 4 to day 28	4-28 days after first day of drug intake
Secondary	Prevalence of chloroquine conferring pfcrt K76T mutation in pre-treatment infections	Proportion of the isolates detected with this specific mutation among isolates at baseline (before study drug initiation)	0 days after first day of drug intake
Secondary	Rates of pre treatment pfcrt K76T mutation in cases of chloroquine treatment failure	Proportion of the isolates detected with this specific mutation at baseline among cases with confirmed treatment failure those	0 days after first day of drug intake
Secondary	Rates of post treatment pfcrt K76T mutation in cases of chloroquine treatment failure	Proportion of the isolates detected as new infections or recrudescent ones with this specific mutation	28 days after first day of drug intake
Secondary	Clearance time of parasitaemia	time in hours until the clearance of parasitemia	28 days after first day of drug intake