Study of ACTs Plus Primaquine for Uncomplicated Plasmodium Vivax Malaria (ACTPQ)

August 28, 2013 updated by: University of Oxford

Comparison of the Efficacy and Safety of Two ACTs Plus Primaquine for Uncomplicated Plasmodium Vivax Malaria in North Sumatera, Indonesia: 1 Year Followup

This randomized clinical trial will be conducted in subjects with uncomplicated Plasmodium vivax malaria during November 2010 to March 2012. The aim of the study is to compare the efficacy and safety of artesunate-amodiaquine plus primaquine (AS-AQ + PQ) and dihydroartemisinin-piperaquine plus primaquine (DHP + PQ) in uncomplicated vivax malaria. The significance of the study is to find alternative drug for treating patients with vivax malaria in case the standard treatment is not available or become resistance. This study will give thorough information about the efficacy and safety of 2 artemisinin-based combination therapies (ACTs) in combination with primaquine. It will also inform the Indonesian Ministry of Health on their suggested policies for radical cure of vivax malaria, and provides evidence based treatment options for chloroquine resistant vivax malaria. This study will also provide information about prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency and G6PD variants in North Sumatera population.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The emergence and spread of drug resistance are major problems in the control of malaria. Resistance to chloroquine in P. vivax was first detected in 1989 then spread to other parts of the world. In Indonesia, resistance of P. vivax to chloroquine has emerged in many parts of the country, ranging from over 50% failure rates in Papua to 20% failure rates in Nias, North Sumatera. Artemisinin derivatives are the most potent and rapidly acting antimalarial drugs available nowadays and also seem to be effective for treatment of vivax malaria, but the number of studies evaluating this is limited. If artemisinin combination therapies (ACTs) are combined with drug that can eliminate parasites in the liver, such as primaquine, this will further optimize the treatment of P. vivax infections. The addition of a course of primaquine will provide radical cure from relapse, and importantly will reduce the transmission of infection because of its gametocyticidal effects. Since 2008, Indonesian government has deployed artesunate-amodiaquine (AS-AQ) as the first line treatment for uncomplicated vivax malaria and promotes radical cure by adding primaquine (PQ). For more than 50 years, Indonesia has used standard dose of primaquine (0.25mg/kg for 14 days) sometimes without prior test of G6PD status of the patients because the screening test is not usually available especially in remote areas. Unfortunately, there is no data to evaluate the safety and efficacy of this standard dose.

Patients with fever or history of fever in preceding 48 hours who are attending the public health centre in study area (study centre) will be examined. Thick and thin blood smear will be taken, stained and examined under light microscope. Slides will be carefully read (according the procedure) for P. vivax malaria. The patients will be assessed by the trial doctor, if they meet all of the inclusion criteria and none of the exclusion criteria, they will receive detail explanation on study & enrolment condition by trial staff. If they agree to participate in the study, they will sign the informed consent form and will be randomized to receive either AS-AQ plus PQ or DHP plus PQ. Essential laboratory tests (hemoglobin, and methemoglobin) will be performed, and filter blood paper for G6PD genotyping will be collected. No patients will be screened for G6PD status. Oral treatment dose will be given under close observation, those who vomit within half an hour will be re-dosed; if they vomit again they will be withdrawn. Patients will be managed as outpatient and be asked to return to the clinic daily, on fourteen consecutive days, days 1-14) to receive physical examination, laboratory test and study treatment and adverse events monitoring, and then weekly on days 21, 28, 35, 42 or any day if feel unwell. Patients who missed their appointments on scheduled day after day 3 will still be included in the study if they appear on the next day (24 hours), or will be visited at home. Patients who develop any acute hemolytic attack symptoms or reduction on hemoglobin during treatment will be closely observed and transfer to hospital for blood transfusion if needed and withdrawn from the study.

After days 42, patients will be visited at home every month (± 1 week from scheduled day will still be accepted) for up to 1 year. Each patient will be given serial number and an appointment card marked with the dates of follow-up.

Study Type

Interventional

Enrollment (Actual)

331

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Indonesia
    • North Sumatera
      • North Sumatra, North Sumatera, Indonesia
        • Labuhan Batu Utara Regency Tanjung leidong village

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Both sex
  • Age > 1 year
  • Fever (axillary temp ≥ 37.5oC) or history of fever during the preceding 48 hours
  • Uncomplicated Plasmodium vivax confirm by microscopic examination
  • Asexual parasite ≥ 250/µL blood
  • Absence of clinical condition that need hospitalization
  • No history of allergy to antimalarial drug
  • Not consuming antibiotic with antimalarial activity

Exclusion Criteria:

  • Clinical features of severe malaria
  • Severe malnutrition
  • Recurrent vomiting
  • Concomitant infection
  • Pregnant (test for β-HCG in women of child bearing age)
  • Lactating mother
  • Move out from study area
  • Not eligible to follow up during study period

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: DHP+PQ
Dihydroartemisinin 2.25mg/kg and piperaquine 16-18mg/kg on day 0, 1, and 2 and primaquine 15 mg/kg form day 0-13.
Drug: Dihydroartemisinin/piperaquine + primaquine
Dihydroartemisinin 2.25mg/kg and piperaquine 16-18mg/kg on day 0, 1, and 2 and primaquine 15 mg/kg form day 0-13.
Active Comparator: AS-AQ +PQ
Standard treatment with artesunate-amodiaquine plus primaquine, with artesunate 4mg/kg and amodiaquine 10mg/kg on day 0, 1, and 2 and primaquine 15 mg/kg form day 0-13.
Drug: Artesunate-amodiaquine + primaquine
Standard treatment with artesunate-amodiaquine plus primaquine, with artesunate 4mg/kg and amodiaquine 10mg/kg on day 0, 1, and 2 and primaquine 15 mg/kg form day 0-13.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Assessment of cure rate of both arms AS-AQ + PQ and DHP+PQ
Time Frame: 42 days
Evaluate the relative efficacy of the study drugs in providing parasite clearance over the observation period of 42 days.
42 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To assess the effects of drugs on parasite clearance and malaria associated symptoms
Time Frame: 42 days

Effect of drug trial on subsequent relapse of Plasmodium vivax. Gametocyte carriage rates. Gametocyte clearance time. Proportion of subjects with fever, parasitemia clearance and increase methemoglobin level.

Hematological recovery. Proportion of subjects with hemolysis.
42 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Oxford

Collaborators

Mahidol University
Indonesia-MoH

Investigators

  • Principal Investigator: Ayodhia Pitaloka Pasaribu, MD, Department of Pediatric, Sumatera Utara University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2011

Primary Completion (Actual)

April 1, 2012

Study Completion (Actual)

April 1, 2012

Study Registration Dates

First Submitted

February 1, 2011

First Submitted That Met QC Criteria

February 1, 2011

First Posted (Estimate)

February 2, 2011

Study Record Updates

Last Update Posted (Estimate)

August 29, 2013

Last Update Submitted That Met QC Criteria

August 28, 2013

Last Verified

August 1, 2013

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BAKMAL1102

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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