Phase II Dose Ranging Study of Artesunate

This study has been completed.
Sponsor:
Collaborators:
Military Infectious Diseases Research Program (MIDRP)
U.S. Army Medical Research and Materiel Command
Information provided by:
Walter Reed Army Institute of Research (WRAIR)
ClinicalTrials.gov Identifier:
NCT00459615
First received: April 10, 2007
Last updated: September 23, 2008
Last verified: September 2008
  Purpose

The purpose of this study is to compare four regimens using US FDA GMP intravenous artesunate for the treatment of uncomplicated Plasmodium falciparum malaria to identify the most effective treatment regimen as determined by rapidity of parasite clearance by microscopy.


Condition Intervention Phase
Falciparum Malaria
Uncomplicated Malaria
Drug: Artesunate for Injection
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind
Primary Purpose: Treatment
Official Title: A Phase II, Randomized, Open-Label, Dose-Ranging Study of Intravenous Artesunate Therapy for the Treatment of Acute, Uncomplicated Plasmodium Falciparum Malaria.

Resource links provided by NLM:


Further study details as provided by Walter Reed Army Institute of Research (WRAIR):

Primary Outcome Measures:
  • The primary endpoint for this pharmacodynamic study is clearance of falciparum parasites from the blood.
  • Reference microscopic interpretation of Giemsa-stained thick and thin blood smears for malaria will serve as the diagnostic method of parasitemia detection.
  • Parasite clearance will be quantified using a discrete variable denoting efficacy to clear at least 90% of asexual parasites from the peripheral blood by 48 hours after administration of IV artesunate

Secondary Outcome Measures:
  • Additional measures of parasite clearance will also be assessed.
  • A continuous variable of time to parasite reduction milestones:
  • parasite clearance time (PCT90 and PCT100), and parasite reduction ratios (PRR12h and PRR24h) at defined time points , and
  • A continuous variable of area under the curve (AUC) of quantifiable parasitemia
  • Tolerability of the treatment regimens will also be assessed throughout the study through use of evaluation for adverse events and safety laboratories to include hematology and chemistry tests.

Estimated Enrollment: 120
Study Start Date: April 2007
Study Completion Date: January 2008
Primary Completion Date: December 2007 (Final data collection date for primary outcome measure)
Detailed Description:

To compare the efficacy and tolerability of intravenous artesunate for the initial treatment of uncomplicated Plasmodium falciparum malaria at doses that bracket anticipated clinical doses (2.4 mg/kg once daily for 3 days; or 2.4 mg/kg initially, at 12 hours on Day 0, and then daily on Day 1 and 2) and thereby establish the safest, highly efficacious dosing regimen for use in future clinical trials.

  Eligibility

Ages Eligible for Study:   12 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Acute symptomatic Plasmodium falciparum malaria infection as determined by malaria smear with a parasite density of ≥ 5000 asexual parasites/mL
  2. Age: 5-65 year old males and females.
  3. Written informed consent must be obtained from adults age > 18 years. Parental consent will be obtained from children and adolescents, and subject assent will also be obtained from adolescents (age 12-17 years).
  4. Willing to stay hospitalized for 4 days for treatment and for 3 scheduled follow-up outpatient visits at Day 7, 14 and 28.

Exclusion Criteria:

  1. Pregnant women (clinically or by positive urine β-HCG) and nursing mothers
  2. Clinical evidence of severe malaria (see Appendix B)
  3. Mixed malaria infection on admission by malaria smear
  4. A previous history of intolerance or hypersensitivity to the study drug artesunate or other artemisinin derivatives or Malarone.
  5. Efficacious malaria drug therapy administered in the past 30 days by history (i.e. quinine, mefloquine, lumefantrine and artemisinin derivatives)
  6. Previous participation in this trial or participation in any other studies involving investigational or marketed products, concomitantly or within 30 days prior to entry in the study.
  7. Laboratory evidence or a history of significant liver or renal functional abnormality.
  8. Anyone who has received a transfusion or any blood product within 30 days
  9. Unable and/or unlikely to comprehend and/or follow the protocol.
  10. Likelihood of requiring treatment during the study period with drugs not permitted by the study protocol.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00459615

Locations
Kenya
New Nyanza Provincial Hospital
Kisumu, Nyanza, Kenya
Thailand
Kwai River Christian Hospital
Sangkhlaburi, Kanchanaburi, Thailand
Sponsors and Collaborators
U.S. Army Office of the Surgeon General
Military Infectious Diseases Research Program (MIDRP)
U.S. Army Medical Research and Materiel Command
Investigators
Principal Investigator: Mark Polhemus, MD USAMRU-K
Principal Investigator: Bryan Smith, MD Armed Forces Research Institute of Medical Sciences, Thailand
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00459615     History of Changes
Other Study ID Numbers: WRAIR 1263, HSRRB Protocol Log#A-13912a,b
Study First Received: April 10, 2007
Last Updated: September 23, 2008
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Malaria
Malaria, Falciparum
Protozoan Infections
Parasitic Diseases
Artesunate
Amebicides
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antimalarials

ClinicalTrials.gov processed this record on July 29, 2014