Pilot Human Study of Tinidazole Efficacy For Radical Cure Of Plasmodium Vivax
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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Pilot Human Study of Tinidazole Efficacy For Radical Cure Of Plasmodium Vivax|
- 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). [ Time Frame: 63 days ] [ Designated as safety issue: No ]
- Recurrence (relapse, recrudescence or re-infection) of Plasmodium vivax between blood stage clearance and 90 days. [ Time Frame: 90 days ] [ Designated as safety issue: No ]
|Study Start Date:||November 2008|
|Study Completion Date:||April 2009|
|Primary Completion Date:||January 2009 (Final data collection date for primary outcome measure)|
|Experimental: Treatment Arm||
2gms, p.o. q.d. for 5 days
Active Comparator: Comparator Arm
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.
|Malaria Research Unit, 68/30 Ban Toong Road, P.O. Box 46|
|Mae Sot, 63110, Tak, Thailand|
|Principal Investigator:||Francois Nosten, MD||Malaria Research Unit, Thailand|