The ASAP Study - Therapeutic Efficacy of Atovaquone-proguanil vs. Artesunate-atovaquone-proguanil in Cambodia
Information source: Armed Forces Research Institute of Medical Sciences, Thailand
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Malaria
Intervention: atovaquone-proguanil (Drug); artesunate-atovaquone-proguanil (Drug)
Phase: Phase 4
Status: Recruiting
Sponsored by: Armed Forces Research Institute of Medical Sciences, Thailand Official(s) and/or principal investigator(s):
Lek Dysoley, MD, Principal Investigator, Affiliation: National Center for Parasitology, Entomology and Malaria Control
Overall contact:
David Saunders, Phone: +66-2696-2791, Email: david.saunders@afrims.org
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).
Clinical Details
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 design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: 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: 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.
Eligibility
Minimum age: 18 Years.
Maximum age: 65 Years.
Gender(s): Both.
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
Locations and Contacts
David Saunders, Phone: +66-2696-2791, Email: david.saunders@afrims.org
Anlong Veng Referral Hospital, Anlong Veng, Oddar Meancheay, Cambodia; Recruiting
DAVID SAUNDERS, MD, MPH
Additional Information
Starting date: December 2014
Last updated: April 17, 2015
|
