The ASAP Study - Therapeutic Efficacy of Atovaquone-proguanil vs. Artesunate-atovaquone-proguanil in Cambodia (ASAP)

March 1, 2021 updated by: Armed Forces Research Institute of Medical Sciences, Thailand

Therapeutic Efficacy of Atovaquone-proguanil and Artesunate-atovaquone-proguanil for the Treatment of Uncomplicated P. Falciparum Malaria in Areas of Multidrug Resistance in Cambodia.

This is a two-arm, randomized, open label Treatment Study evaluating the therapeutic efficacy, safety, tolerability and pharmacokinetics of a three-day course of Atovaquone-Proguanil (AP) or a three-day course of Atovaquone-Proguanil combined with 3 days of Artesunate (ASAP) in patients with uncomplicated Plasmodium falciparum malaria at selected sites in Cambodia. Atovaquone-proguanil, soon to adopted as a first line antimalarial agent by the National Malaria Control Program (CNM) in Cambodia in provinces with confirmed multidrug resistance, will be given with or without artesunate (AS) as a directly observed, standard three-day fixed dose combination treatment to all volunteers enrolled. The efficacy and safety of both drug combination as well as evidence for in vivo and in vitro resistance to their components will be monitored during the treatment period. All volunteers will receive a single dose of 15mg of primaquine as recommended by WHO with the first dose of AP or ASAP to block the transmission of malaria to mosquitoes. Resistance to AP and ASAP will be assessed by a combination of clinical, pharmacologic, and parasitological parameters including genomic signatures of selection during careful weekly follow-up visits for 6 weeks. Investigators will also be able to evaluate the effects of primaquine on the sexual stages of malaria (gametocytes).

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

205

Phase

  • Phase 4

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

  • Cambodia
    • Oddar Meancheay
      • Anlong Veng, Oddar Meancheay, Cambodia
        • Anlong Veng Referral Hospital

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

16 years to 63 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Male or female with uncomplicated P. falciparum malaria (volunteers with mixed P. falciparum and P. vivax infections may be enrolled), 18-65 years of age
  2. Baseline asexual parasite density between 100-200,000 parasites/microL
  3. Able to provide informed consent
  4. Available and agree to follow-up for anticipated study duration including 3 day treatment course at the Medical Treatment Facility, and weekly follow-up for the 42-day period.

Exclusion Criteria:

  1. Allergic reaction or medical contraindication to atovaquone, proguanil, artesunate or primaquine, to include a calculated serum creatinine clearance estimate of less than 30mL/min
  2. Significant acute comorbidity requiring urgent medical intervention
  3. Signs/symptoms and parasitological confirmation of severe malaria
  4. Use of any anti-malarial within the past 7 days, or atovaquone-proguanil in the past 30 days
  5. Use of the following concomitant medications within 7 days, which may cause or be volunteers to significant drug-drug interactions with study drug - tetracycline, metoclopramide, rifampin, rifabutin, zidovudine or etoposide.
  6. Pregnant or lactating female, or female of childbearing age, up to 50 years of age, who does not agree to use an acceptable form of contraception during the study
  7. Judged by the investigator to be otherwise unsuitable for study participation

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
Active Comparator: atovaquone-proguanil (AP)
A standard fixed-dose 3 day regimen of Atovaquone-proguanil (AP) for treatment of uncomplicated P. falciparum malaria.
Drug: atovaquone-proguanil
A daily fixed dose combination of 4 tablets containing atovaquone 250mg and proguanil hydrochloride 100mg (total 1000mg/400mg respectively)
Active Comparator: artesunate-atovaquone-proguanil (ASAP)
A standard fixed-dose 3 day regimen of Atovaquone-proguanil (AP) plus 3 days of artesunate (200mg per day) for treatment of uncomplicated P. falciparum malaria.
Drug: artesunate-atovaquone-proguanil
A daily fixed dose combination of 4 tablets containing atovaquone 250mg and proguanil hydrochloride 100mg (total 1000mg/400mg daily respectively) in addition to 4 tablets containing 50mg artesunate (200mg daily)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Efficacy at 42 days (with 95% confidence intervals) for AP with and without artesunate for uncomplicated P. falciparum diagnosed by positive PCR-corrected malaria microscopy.
Time Frame: 6 weeks
6 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
Efficacy at 28 days (with 95% confidence intervals) for atovaquone-proguanil and artesunate-atovaquone-proguanil for uncomplicated P. falciparum diagnosed by positive PCR-corrected malaria microscopy.
Time Frame: 4 weeks
4 weeks
Rates of sexual stage infections at days 1, 4, week 1 and week 2 based on a combined endpoint of light microscopy and PCR analysis for detection of gametocyte maturity.
Time Frame: 2 weeks
2 weeks
Comparative rates, duration and intensity of treatment-related adverse drug events, and total adverse events in each treatment group.
Time Frame: 6 weeks
6 weeks

Collaborators and Investigators

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

Sponsor

Armed Forces Research Institute of Medical Sciences, Thailand

Collaborators

National Centre for Parasitology, Entomology and Malaria Control, Cambodia
Naval Medical Research Center, Asia (NMRC-A)

Investigators

  • Principal Investigator: Lek Dysoley, MD, National Center for Parasitology, Entomology and Malaria Control
  • Principal Investigator: Mariusz Wojnarski, MD, Armed Forces Research Institute of Medical Sciences (AFRIMS)

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

December 1, 2014

Primary Completion (Actual)

December 1, 2015

Study Completion (Anticipated)

December 1, 2021

Study Registration Dates

First Submitted

October 18, 2014

First Submitted That Met QC Criteria

November 19, 2014

First Posted (Estimate)

November 21, 2014

Study Record Updates

Last Update Posted (Actual)

March 2, 2021

Last Update Submitted That Met QC Criteria

March 1, 2021

Last Verified

March 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • WR2115

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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