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Antimalarial Drug Resistance With Assessment of Transmission Blocking Activity

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ClinicalTrials.gov Identifier: NCT01849640
Recruitment Status : Suspended (Poor efficacy of DHA-piperaquine due to likely drug resistance.)
First Posted : May 8, 2013
Last Update Posted : July 15, 2015
Sponsor:
Collaborators:
National Centre for Parasitology, Entomology and Malaria Control, Cambodia
Royal Cambodian Armed Forces
US Department of Defense Armed Forces Health Surveillance Center
Information provided by (Responsible Party):
David Saunders, Armed Forces Research Institute of Medical Sciences, Thailand

Brief Summary:
This is a two-arm, open label Treatment Study comparing the efficacy, safety, tolerability and pharmacokinetics of a three-day course of Dihydroartemisinin-Piperaquine (DP) with or without single-dose primaquine in patients with uncomplicated Plasmodium falciparum malaria. On the last day of DP therapy, volunteers will be randomized to receive either a single 45 mg dose of primaquine (PQ) or DP treatment only (no primaquine).

Condition or disease Intervention/treatment Phase
Uncomplicated Plasmodium Falciparum Malaria Drug: DHA-piperaquine and Primaquine Not Applicable

Detailed Description:
Volunteers with uncomplicated malaria in Cambodia will be enrolled to current standard of care therapy with DHA-piperaquine to monitor therapeutic efficacy and measure resistance. The cardiac safety of piperaquine will be monitored with electrocardiograms during the treatment period. Resistance to DP and DP-PQ will be assessed by a combination of clinical, pharmacologic, and parasitologic parameters including genomic signatures of selection during careful weekly follow-up visits for 42 days. Volunteers will be randomized on day 3 to either a single 45mg dose of primaquine or no sexual stage therapy to evaluate effects of primaquine on the sexual stages of malaria (gametocytes) and potential transmissibility of infection to Anopheles mosquitoes as compared to those not treated with primaquine.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Active Surveillance for P. Falciparum Drug Resistance With Assessment of Transmission Blocking Activity of Single Dose Primaquine in Cambodia
Study Start Date : December 2012
Actual Primary Completion Date : December 2014
Estimated Study Completion Date : June 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Malaria

Arm Intervention/treatment
Active Comparator: DHA-piperaquine with Primaquine
3-day treatment course of DHA-piperaquine with 45mg single dose primaquine
Drug: DHA-piperaquine and Primaquine
Subject will be enrolled in open label fashion to a 3-day treatment course of DHA-piperaquine (DP) by directly observed therapy (DOT, all patients will receive a total of 9 tablets containing 40mg DHA and 320mg of piperaquine in divided doses at 0, 24 and 48 hours (3 tablets once per day) for the 3 day course. At completion of DP treatment volunteers will be randomized in an open label fashion to receive a single 45 mg dose of primaquine or no therapy.

Active Comparator: DHA-piperaquine without Primaquine
3-day treatment course of DHA-piperaquine
Drug: DHA-piperaquine and Primaquine
Subject will be enrolled in open label fashion to a 3-day treatment course of DHA-piperaquine (DP) by directly observed therapy (DOT, all patients will receive a total of 9 tablets containing 40mg DHA and 320mg of piperaquine in divided doses at 0, 24 and 48 hours (3 tablets once per day) for the 3 day course. At completion of DP treatment volunteers will be randomized in an open label fashion to receive a single 45 mg dose of primaquine or no therapy.




Primary Outcome Measures :
  1. Clinical efficacy of DP [ Time Frame: 3 years ]
    Efficacy rates at 42 days (with 95% confidence intervals) for DP with and without single dose primaquine for uncomplicated P. falciparum diagnosed by positive PCR-corrected malaria microscopy.


Secondary Outcome Measures :
  1. Efficacy of Primaquine to treat sexual stage gametocyte infection and prevent transmission of P. falciparum gametocytes to mosquitoes. [ Time Frame: 3 years ]
    To detect efficacy of a onetime dose of primaquine after completion of therapy for blood stage infection on gametocytemia that may persist after DP treatment by using comparative rates of sexual stage infections between patients dosed with and without primaquine based on a composite endpoint of light microscopy and PCR detection and staging of gamteocytes with mosquito membrane feeding assay to detect oocysts in sterile lab-reared mosquitoes.



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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. Volunteer 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 1,000-200,000 parasites/uL
  3. Able to provide informed consent
  4. Available and agree to follow-up for anticipated study duration including 3 day treatment course at the MTF and weekly follow-up for the 42-day period
  5. Authorized by local commander to participate if active duty military

Exclusion Criteria:

  1. Allergic reaction or contraindication to DHA, piperaquine or primaquine
  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 14 days.
  5. Class I or II G6PD deficiency (defined as severe) as determined at screening
  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. Clinically significant abnormal EKG, including a QTcF interval > 500 ms at enrollment.
  8. Known or suspected concomitant use of QTc prolonging medications.
  9. 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): NCT01849640


Locations
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Cambodia
Anlong Veng Referral Hospital
Anlong Veng, Oddormean Chey, Cambodia
Sponsors and Collaborators
David Saunders
National Centre for Parasitology, Entomology and Malaria Control, Cambodia
Royal Cambodian Armed Forces
US Department of Defense Armed Forces Health Surveillance Center
Investigators
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Principal Investigator: David Saunders, MD, MPH Dept. of Immunology and Medicine, Armed Forces Research Institute of Medical Sciences (AFRIMS)

Additional Information:
Publications of Results:
Other Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: David Saunders, David Saunders, LTC, MC, USA, Armed Forces Research Institute of Medical Sciences, Thailand
ClinicalTrials.gov Identifier: NCT01849640     History of Changes
Other Study ID Numbers: WRAIR#1877
HRPO Log Number A-17145 ( Other Identifier: USAMRMC ORP HRPO )
First Posted: May 8, 2013    Key Record Dates
Last Update Posted: July 15, 2015
Last Verified: July 2015

Keywords provided by David Saunders, Armed Forces Research Institute of Medical Sciences, Thailand:
Malaria
Drug resistance
DHA-piperaquine
Cambodia
Transmission Blocking

Additional relevant MeSH terms:
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Malaria
Malaria, Falciparum
Protozoan Infections
Parasitic Diseases
Primaquine
Piperaquine
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents