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

NCT ID: NCT02297477

Last Updated: 2021-03-02

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 205 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-12-31
• Study Completion Date: 2021-12-31

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).

Conditions

Malaria

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

atovaquone-proguanil (AP)

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

Group Type: ACTIVE_COMPARATOR

atovaquone-proguanil

Intervention Type: DRUG

A daily fixed dose combination of 4 tablets containing atovaquone 250mg and proguanil hydrochloride 100mg (total 1000mg/400mg respectively)

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.

Group Type: ACTIVE_COMPARATOR

artesunate-atovaquone-proguanil

Intervention Type: DRUG

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)

Interventions

atovaquone-proguanil

A daily fixed dose combination of 4 tablets containing atovaquone 250mg and proguanil hydrochloride 100mg (total 1000mg/400mg respectively)

Intervention Type: 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)

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Centre for Parasitology, Entomology and Malaria Control, Cambodia

OTHER

Sponsor Role: collaborator

Naval Medical Research Center, Asia (NMRC-A)

UNKNOWN

Sponsor Role: collaborator

Armed Forces Research Institute of Medical Sciences, Thailand

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lek Dysoley, MD

Role: PRINCIPAL_INVESTIGATOR

National Center for Parasitology, Entomology and Malaria Control

Mariusz Wojnarski, MD

Role: PRINCIPAL_INVESTIGATOR

Armed Forces Research Institute of Medical Sciences (AFRIMS)

Locations

Anlong Veng Referral Hospital

Anlong Veaeng, Oddar Meancheay, Cambodia

Countries

Cambodia

Other Identifiers

WR2115

Identifier Type: -

Identifier Source: org_study_id