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

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ClinicalTrials.gov Identifier: NCT02297477
Recruitment Status : Active, not recruiting
First Posted : November 21, 2014
Last Update Posted : February 13, 2018
Sponsor:
Collaborators:
National Centre for Parasitology, Entomology and Malaria Control, Cambodia
Naval Medical Research Center, Asia (NMRC-A)
Information provided by (Responsible Party):
Armed Forces Research Institute of Medical Sciences, Thailand

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).

Condition or disease Intervention/treatment Phase
Malaria Drug: atovaquone-proguanil Drug: artesunate-atovaquone-proguanil Phase 4

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 205 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : December 2014
Actual Primary Completion Date : December 2015
Estimated Study Completion Date : February 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Malaria

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)




Primary Outcome Measures :
  1. 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 Measures :
  1. 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 ]
  2. 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 ]
  3. Comparative rates, duration and intensity of treatment-related adverse drug events, and total adverse events in each treatment group. [ Time Frame: 6 weeks ]


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02297477


Locations
Cambodia
Anlong Veng Referral Hospital
Anlong Veng, Oddar Meancheay, Cambodia
Sponsors and Collaborators
Armed Forces Research Institute of Medical Sciences, Thailand
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)

Responsible Party: Armed Forces Research Institute of Medical Sciences, Thailand
ClinicalTrials.gov Identifier: NCT02297477     History of Changes
Other Study ID Numbers: WR2115
First Posted: November 21, 2014    Key Record Dates
Last Update Posted: February 13, 2018
Last Verified: February 2018

Additional relevant MeSH terms:
Antimalarials
Malaria
Protozoan Infections
Parasitic Diseases
Artesunate
Artemisinins
Atovaquone
Proguanil
Atovaquone, proguanil drug combination
Amebicides
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimetabolites