Evaluating the Role of Chloroquine for Malaria Elimination

NCT02698748 | Completed Phase 2

• 1 other identifier: CNBS (173/CNBS/13)
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

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 ®).

Conditions

Malaria

Keywords

Chloroquine; Malaria Elimination; P.falciparum; Clinical Trial; Mozambique; Adults

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Early parasitologic failure

  1-3 days after first day of drug intake

• Late parasitologic failure

  4-28 days after first day of drug intake

• Prevalence of chloroquine conferring pfcrt K76T mutation in pre-treatment infections

  0 days after first day of drug intake

• Rates of pre treatment pfcrt K76T mutation in cases of chloroquine treatment failure

  0 days after first day of drug intake

• Rates of post treatment pfcrt K76T mutation in cases of chloroquine treatment failure

  28 days after first day of drug intake

Study Arms (2)

Chloroquine

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Interventions

Chloroquine 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).

Also known as: Chloroquine Phosphate

Chloroquine

Placebo 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

Also known as: Placebo capsules

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Centro de Investigacao em Saude de Manhica: lead

Study Sites (1)

Centro de Investigaçao em Saude de Manhiça

Manhiça, Maputo Province, 1902, Mozambique

Location

Related Publications (2)

• 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.

  PMID: 29546346 DERIVED

• 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.

  PMID: 28465550 DERIVED

MeSH Terms

Conditions

Malaria

Interventions

Chloroquine; chloroquine diphosphate

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Pedro Aide, MD, MSc, PhD

  Centro de Investigação em Saude de Manhiça

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 13, 2015
• First Posted: March 4, 2016
• Study Start: January 1, 2015
• Primary Completion: April 1, 2015
• Study Completion: June 1, 2015
• Last Updated: February 7, 2018

Record last verified: 2016-02

Locations

MO (1)