Malaria, VivaxPhase 2NCT00811096
Pilot Human Study of Tinidazole Efficacy For Radical Cure Of Plasmodium Vivax
A Phase 2 study testing Tinidazole and chloroquine in people with Malaria, Vivax, run by Walter Reed Army Institute of Research (WRAIR) at 1 site in Thailand.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Malaria, Vivax
- What is being tested?
- Tinidazole and chloroquine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteThailand
- Study dates
- Nov 2008to Apr 2009
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 9Show fewer
- 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%.
Trial locations and contacts
1 site in 1 country.
Thailand1 site
Malaria Research Unit, 68/30 Ban Toong Road, P.O. Box 46
Mae Sot, Changwat Tak
About this study
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.
Read the 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.
- Conditions
- Malaria, Vivax
- Being tested
- Tinidazole, chloroquine
- Keywords
- Malaria, Vivax/*drug therapy, Tinidazole/pharmacology/*therapeutic use, Recurrence, Plasmodium vivax/*drug effects
- Medical subject headings
- Malaria, Vivax, Malaria, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TinidazoleDrug
2gms, p.o. q.d. for 5 days
chloroquineDrug
| Study group | Role | What they receive |
|---|---|---|
| Treatment Arm | Experimental | Not described Receives: Drug: Tinidazole |
| Comparator Arm | Active comparator | Comparator Arm Receives: Drug: chloroquine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 63 days
Secondary outcomes (1)
Recurrence (relapse, recrudescence or re-infection) of Plasmodium vivax between blood stage clearance and 90 days.
Measured: 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Dec 2008 (estimated)
- Study startNov 2008
- Primary completionJan 2009
- Study completionApr 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Malaria, VivaxStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Walter Reed Army Institute of Research (WRAIR)
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Francois Nosten, MD, Principal investigator, Malaria Research Unit, Thailand
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00811096
- Sponsor's protocol ID
- 1477
- Other IDs
- HRPO Log#(A-15176);, Mahidol (TMEC 08-042)
- Status last verified
- Nov 2012
- First submitted
- 17 Dec 2008
- Last updated
- 3 Dec 2012
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Macareo L, Lwin KM, Cheah PY, Yuentrakul P, Miller RS, Nosten F. Triangular test design to evaluate tinidazole in the prevention of Plasmodium vivax relapse. Malar J. 2013 May 29;12:173. doi: 10.1186/1475-2875-12-173.
PubMed 23718705
Study at a glance
From the registry record, last updated by the sponsor on 3 Dec 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Human Study of Tinidazole Efficacy For Radical Cure Of Plasmodium Vivax
- ClinicalTrials.gov ID
- NCT00811096
- Acronym / sponsor ID
- 1477
- Conditions
- Malaria, Vivax
- Keywords
- Malaria, Vivax/*drug therapy, Tinidazole/pharmacology/*therapeutic use, Recurrence, Plasmodium vivax/*drug effects
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Walter Reed Army Institute of Research (WRAIR)US federal agency
- Study start
- Nov 2008
- Primary completion
- Jan 2009 (actual)
- Study completion
- Apr 2009 (actual)
- First posted
- 18 Dec 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment Arm | Experimental | Drug: Tinidazole |
| Comparator Arm | Active comparator | Drug: chloroquineComparator Arm |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tinidazole2gms, p.o. q.d. for 5 days | Drug | Treatment Arm |
| chloroquine | Drug | Comparator Arm |
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).
Time frame: 63 days
1 secondary outcome
Recurrence (relapse, recrudescence or re-infection) of Plasmodium vivax between blood stage clearance and 90 days.
Time frame: 90 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Dec 2012.
- Derived from this study: PubMed 23718705Macareo L, Lwin KM, Cheah PY, Yuentrakul P, Miller RS, Nosten F. Triangular test design to evaluate tinidazole in the prevention of Plasmodium vivax relapse. Malar J. 2013 May 29;12:173. doi: 10.1186/1475-2875-12-173.
Related trials for Malaria, Vivax
Not yet recruiting
Positron Emission Tomography and Organ-Specific Changes in Participants Co-Enrolled in NIH Studies of Plasmodium Vivax Controlled Human Malaria Infection
Healthy Volunteer, Malaria
Not yet recruiting
Three-arm Cluster Randomised Control Trial Evaluation of Guardian Spatial Emanator as a Complimentary Vector Control Tool in Papua New Guinea
Malaria
RecruitingPhase 1
Induced Blood-Stage Malaria in Healthy Malaria-Naive Adults to Assess the Safety and Infectivity of Plasmodium Vivax Challenge Agent and Evaluate Transmission in Mosquito Feeding Assays
Malaria
Not yet recruitingPhase 1
Safety and Immunogenicity of the Recombinant Malaria Vaccines in Healthy Adults Aged 18-50 Years
Malaria Vaccine
Not yet recruitingPhase 2
This is a Clinical Study to Assess Whether the Combination of SJ733 and Tafenoquine Will be a Safe and Rapidly Acting Anti-malarial for the Radical Cure of P. Vivax Malaria
Malaria, Malaria Vivax
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Francois Nosten, MD principal investigator
Malaria Research Unit, Thailand
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tinidazole and chloroquine in people with Malaria, Vivax, run by Walter Reed Army Institute of Research (WRAIR) at 1 site in Thailand.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Dec 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Thailand. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00811096, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Dec 2012.