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

Primary Purpose

Malaria

Status
Unknown status
Phase
Phase 4
Locations
Cambodia
Study Type
Interventional
Intervention
atovaquone-proguanil
artesunate-atovaquone-proguanil
Sponsored by
Armed Forces Research Institute of Medical Sciences, Thailand
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Malaria

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Anlong Veng Referral Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

atovaquone-proguanil (AP)

artesunate-atovaquone-proguanil (ASAP)

Arm Description

A standard fixed-dose 3 day regimen of Atovaquone-proguanil (AP) for treatment of uncomplicated P. falciparum malaria.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
Comparative rates, duration and intensity of treatment-related adverse drug events, and total adverse events in each treatment group.

Full Information

First Posted
October 18, 2014
Last Updated
March 1, 2021
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)
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1. Study Identification

Unique Protocol Identification Number
NCT02297477
Brief Title
The ASAP Study - Therapeutic Efficacy of Atovaquone-proguanil vs. Artesunate-atovaquone-proguanil in Cambodia
Acronym
ASAP
Official Title
Therapeutic Efficacy of Atovaquone-proguanil and Artesunate-atovaquone-proguanil for the Treatment of Uncomplicated P. Falciparum Malaria in Areas of Multidrug Resistance in Cambodia.
Study Type
Interventional

2. Study Status

Record Verification Date
March 2021
Overall Recruitment Status
Unknown status
Study Start Date
December 2014 (undefined)
Primary Completion Date
December 2015 (Actual)
Study Completion Date
December 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the 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)

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malaria

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
205 (Actual)

8. Arms, Groups, and Interventions

Arm Title
atovaquone-proguanil (AP)
Arm Type
Active Comparator
Arm Description
A standard fixed-dose 3 day regimen of Atovaquone-proguanil (AP) for treatment of uncomplicated P. falciparum malaria.
Arm Title
artesunate-atovaquone-proguanil (ASAP)
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
atovaquone-proguanil
Intervention Description
A daily fixed dose combination of 4 tablets containing atovaquone 250mg and proguanil hydrochloride 100mg (total 1000mg/400mg respectively)
Intervention Type
Drug
Intervention Name(s)
artesunate-atovaquone-proguanil
Intervention Description
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)
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
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
Title
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
Title
Comparative rates, duration and intensity of treatment-related adverse drug events, and total adverse events in each treatment group.
Time Frame
6 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Baseline asexual parasite density between 100-200,000 parasites/microL Able to provide informed consent 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: Allergic reaction or medical contraindication to atovaquone, proguanil, artesunate or primaquine, to include a calculated serum creatinine clearance estimate of less than 30mL/min Significant acute comorbidity requiring urgent medical intervention Signs/symptoms and parasitological confirmation of severe malaria Use of any anti-malarial within the past 7 days, or atovaquone-proguanil in the past 30 days 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. 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 Judged by the investigator to be otherwise unsuitable for study participation
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lek Dysoley, MD
Organizational Affiliation
National Center for Parasitology, Entomology and Malaria Control
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Mariusz Wojnarski, MD
Organizational Affiliation
Armed Forces Research Institute of Medical Sciences (AFRIMS)
Official's Role
Principal Investigator
Facility Information:
Facility Name
Anlong Veng Referral Hospital
City
Anlong Veng
State/Province
Oddar Meancheay
Country
Cambodia

12. IPD Sharing Statement

Learn more about this trial

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

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