Safety and Efficacy of Chloroquine and Primaquine for Vivax Malaria in Bhutan

Parasitic Clearance and Recurrence Rates Among Patients With Vivax Malaria on Chloroquine and Primaquine Therapy

This research is intended to study the efficacy of chloroquine (CQ) and primaquine (PQ) for Plasmodium vivax (P.vivax) infection, and also to study the recurrence rate among patients with P.vivax malaria on standard doses of CQ and PQ. For this study, PQ will be withheld for 28 days so as to study the efficacy of CQ alone.

This study will assess whether CQ is still effective against P.vivax or whether there are resistant P.vivax strains in Bhutan.

Study Overview

• Status: Completed
• Conditions: Vivax Malaria
• Intervention / Treatment: Drug: Primaquine; Drug: Chloroquine

Detailed Description

This study aims to assess the efficacy of Chloroquine alone, withholding Primaquine until day 28. Parasitic clearance and recurrence rates will be recorded. Patients whose blood stage of parasites are not cleared with the standard dose of Chloroquine, or any recurrences before day 28, will be treated with second line treatment (ACT).

The patients blood level of Chloroquine (drug concentration) at the time of a recrudescent infection will de determined to assess whether that could be due to resistance, or due to low level of Chloroquine.

Any relapses occurring after day 28 when not receiving Primaquine, or after completion of Primaquine dosage for a total of 14 days (from day 29 to 42), will be treated with repeat doses of the initial treatment. The recurrence rates will be recorded so as to develop the next phase of the study where the two different doses of Primaquine (high dose vs. low dose) will be compared.

• Study Type: Observational
• Enrollment (Actual): 24

Contacts and Locations

Study Locations

• Bhutan
  • Gelephu, Bhutan
    • Vector Diseases Control Program

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with P.vivax infections will be recruited from 6 sentinel sites and will be recruited for the study after informed consent is received.

An amendment has been approved to extend the study to 12 sites.

Description

Inclusion Criteria:

• >12 months of age
• infection with P.vivax parasitaemia monoinfection
• presence of axillary temperature >37.5 degrees or history of fever during the past 24 hours
• ability to swallow oral medication
• ability and willingness to comply with the study protocol for the duration of the study, including 12 months follow up
• informed consent from the patient/parent/guardian in the case of children

Exclusion Criteria:

• Presence of general danger signs in children aged under 5 years or signs of severe malaria according to the definitions of WHO
• Presence of severe malnutrition (defined as a child whose growth standard is below -3 z-score, has symmetrical oedema involving at least the feet or has a mid-upper arm circumference < 110 mm);
• History of haemolysis or severe anaemia
• Acute anaemia <7 mg/dL
• Presence of febrile conditions due to diseases other than malaria (e.g. measles, acute lower respiratory tract infection, severe diarrhoea with dehydration) or other known underlying chronic or severe diseases (e.g. cardiac, renal and hepatic diseases, HIV/AIDS);
• Regular medication, which may interfere with antimalarial pharmacokinetics
• History of hypersensitivity reactions or contraindications to any of the medicine(s) being tested or used as alternative treatment(s)
• a positive pregnancy test or lactating

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Chloroquine and Primaquine; Chloroquine (CQ)10mg/kg for day 1, 2 and 5mg/kg for day 3 Primaquine (PQ)0.25mg/kg/day for 14 days	Drug: Primaquine; Drug: Chloroquine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Chloroquine efficacy for P.vivax infections in Bhutan.	The purpose is to study the efficacy of Chloroquine alone by recording recrudescent rates and parasitic clearance in P.vivax patients who are given a standard dose of Chloroquine treatment.	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To study the efficacy of Primaquine.	In this study, Primaquine will be administered on day 28, and any relapse will be recorded to study relapse rates over a 12 month period.	Patients with recurrence after day 28 will be recorded.

Other Outcome Measures

Outcome Measure	Time Frame
To assess the feasibility of a 12 month follow-up of patients with vivax malaria in Bhutan.	12 months
To assess the safety of the currently prescribed CQ and PQ regimens in Bhutan.	12 months

Collaborators and Investigators

• Sponsor: Menzies School of Health Research
• Collaborators: Ministry of Health, Bhutan

Study record dates

Study Major Dates

• Study Start: January 1, 2013
• Primary Completion (Actual): October 1, 2015
• Study Completion (Actual): October 1, 2015

Study Registration Dates

• First Submitted: October 25, 2012
• First Submitted That Met QC Criteria: October 26, 2012
• First Posted (Estimate): October 29, 2012

Study Record Updates

• Last Update Posted (Estimate): May 27, 2016
• Last Update Submitted That Met QC Criteria: May 26, 2016
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Malaria; Malaria, Vivax; Anti-Infective Agents; Antirheumatic Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Amebicides; Chloroquine; Primaquine
• Other Study ID Numbers: Bhutan_APMEN_CQ PQ_2013