Pilot Human Study of Tinidazole Efficacy For Radical Cure Of Plasmodium Vivax
Information source: Walter Reed Army Institute of Research (WRAIR)
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Malaria, Vivax
Intervention: Tinidazole (Drug); chloroquine (Drug)
Phase: Phase 2
Status: Completed
Sponsored by: Walter Reed Army Institute of Research (WRAIR) Official(s) and/or principal investigator(s): Francois Nosten, MD, Principal Investigator, Affiliation: Malaria Research Unit, Thailand
Summary
Assess the efficacy of 2 grams of tinidazole given for 5 days with standard dose chloroquine
to achieve radical cure of Plasmodium vivax within a 90 day follow-up period sufficient to
justify an IND and formal phase II evaluation.
Clinical Details
Official title: Pilot Human Study of Tinidazole Efficacy For Radical Cure Of Plasmodium Vivax
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Cure is defined as absence of malaria infection on thick/thin malaria smears up to and on day 63 after initial clearance of parasitemia. Subjects will be followed to day 90 to rule out delayed presentation of malaria (as opposed to cure).
Secondary outcome: Recurrence (relapse, recrudescence or re-infection) of Plasmodium vivax between blood stage clearance and 90 days.
Detailed description:
This is a randomized, open-label study that will treat adult subjects with Plasmodium vivax
infection with chloroquine for 3 days and tinidazole for 5 days concomitantly to assess
efficacy for radical cure (clearance of blood and liver stages of infection). There will be
randomization to a positive comparator arm treated with chloroquine and primaquine
(definitive radical cure) in order to obtain an estimate of the rate of re-infection during
the monitoring period in the study population.
A simple randomization procedure will assign subjects to one of the two arms (treatment arm
or comparator arm). The ratio of assignment will be 2: 1, treatment arm to the comparator
arm. The exact number assigned to the treatment arm will vary depending on the initial
outcome of early enrollees per the sequential analysis design of the trial. In the worse
case scenario of no clear trend developing early, no more than 50 subjects will be required
to complete the trial in the study drug arm in order to arrive at a conclusion regarding the
study drug.
Follow-up period will be for 90 days. This will allow us to capture essentially all early
relapses that would occur under normal circumstances, as well as assess if tinidazole may
delay but not fully eliminate recurrence. Subjects without a recurrence at 90 days will be
considered to have achieved radical cure.
This study will use a modified triangular test, a form of sequential analysis designed to
enable repeated statistical analyses throughout the study recruitment period, while
maintaining a pre-specified power and type I error. The trial can be stopped as soon as the
information accumulated is considered sufficient to reach a conclusion and it will limit
enrollment and exposure to a failing treatment regimen.
Results of this study will be sufficient to determine whether tinidazole should be
designated as an "early kill" (an ineffective drug for vivax malaria radical cure with no
future evaluation) or whether it is sufficiently efficacious to warrant further investment
with an IND and formal phase II study to seek an SNDA.
Eligibility
Minimum age: 18 Years.
Maximum age: 65 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Adult male and non-pregnant female volunteers that can communicate in the Burmese or
Karen language.
- Age: Between 18 and 65 years (inclusive).
- Acute, symptomatic, blood smear positive diagnosis of Plasmodium vivax
mono-infection.
- Ability to comprehend and comply with the requirements of the protocol.
- Willing to provide written informed consent.
- Willing to abstain from alcohol (EtOH) use during initial treatment and for 72 hours
thereafter.
- Sexually active females must test negative on urine pregnancy test and must be
counseled on an effective method of avoiding pregnancy (e. g., intrauterine
contraceptive device; oral contraceptives; diaphragm or condom in combination with
contraceptive jelly, cream or foam; Norplant® or Depo-Provera®), be surgically
sterile, be post-menopause for at least one year, or be monogamous with a sterile
sexual partner for at least 15 days prior to dosing with study product and at least
72 hours after their last dose of test drug.
Exclusion Criteria:
- Subjects positive for G6PD deficiency.
- Pregnant women (clinically or by positive urine β-HCG) and nursing mothers.
- Concomitant use of metronidazole, albendazole or mebendazole.
- Any malaria treatment or use of azithromycin or other macrolides, tetracyclines,
sulfonamides, doxycycline, tetracycline or other sulfa based or other drug with
antimalarial activity for the previous 4 weeks prior to screening. Additionally,
concomitant use of phenobarbitol, rifampin, phenytoin, fosphenytoin, cimetidine,
ketoconazole, cholestryramine constitute exclusion criteria.
- Significant health problems, including, but not limited to significant, cardiac,
renal or liver disease or lab abnormalities and those subjects in whom it is
suspected that they will not abstain from alcohol use during treatment and for the
subsequent 3 days.
- Mixed malaria infection on admission determined by malaria smear and/or any positive
HRP2 antigen testing.
- A previous history of significant intolerance or hypersensitivity to the study drug
tinidazole or to chloroquine or primaquine. (nausea alone from previous primaquine
use will not be an excluding factor unless subject was unable to complete a
primaquine course due to this discomfort.)
- Subjects that have received transfusions within the previous 30 days.
- Presenting hematocrit <25%.
Locations and Contacts
Malaria Research Unit, 68/30 Ban Toong Road, P.O. Box 46, Mae Sot, 63110, Tak, Thailand
Additional Information
Starting date: November 2008
Last updated: November 30, 2012
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