Ignite Creation Date:
2024-05-05 @ 5:03 PM
Last Modification Date:
2024-10-26 @ 9:27 AM
Study NCT ID:
NCT00376012
Status:
UNKNOWN
Last Update Posted:
2008-06-11
First Post:
2006-09-13
Brief Title:
Short Course Intermittent Regimens for the Treatment of HIV-Associated Tuberculosis
Sponsor:
Tuberculosis Research Centre India
Organization:
Tuberculosis Research Centre India
Study Overview
Official Title:
Randomized Clinical Trial to Assess the Efficacy of Short Course Intermittent Regimens for the Treatment of HIV-Associated Tuberculosis
Status:
UNKNOWN
Status Verified Date:
2008-05
Last Known Status:
ACTIVE_NOT_RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Title Randomized clinical trial to assess the efficacy of short course intermittent regimens for the treatment of HIV-associated tuberculosis
Phase Phase III trial
Population 300 HIV positive patients with tuberculosis
Number of SitesFour
1 Tuberculosis Research Centre Chennai
2 Government General Hospital Chennai
3 Government Hospital of Thoracic Medicine Tambaram
4 Government Rajaji Hospital Madurai
Study Duration36 months
Study ObjectiveTo study the efficacy of the standard RNTCP Category I regimen 2EHRZ3 4RH3 the control arm vs an extended continuation phase regimen 2EHRZ3 7 RH3 in the treatment of pulmonary and extrapulmonary TB in the HIV positive patients
2 To study the relationship between stage of HIV disease and response to anti-TB treatment
3 To study recurrences and their nature relapsere-infection in detail by using RFLP analysis
Study DesignIt is a two armed prospective randomized open label controlled clinical trial with stratified random allocation based on CD4 count and sputum smear grade
All enrolled patients will be treated according to the RNTCP guidelines during the intensive phase In the continuation phase Cat I patients will be stratified by CD4 counts and by smear grade and randomly allocated either to the standard RNTCP regimen or to an alternative extended regimen 2EHRZ34RH3 or 2EHRZ37RH3
Phase Phase III trial
Population 300 HIV positive patients with tuberculosis
Number of SitesFour
1 Tuberculosis Research Centre Chennai
2 Government General Hospital Chennai
3 Government Hospital of Thoracic Medicine Tambaram
4 Government Rajaji Hospital Madurai
Study Duration36 months
Study ObjectiveTo study the efficacy of the standard RNTCP Category I regimen 2EHRZ3 4RH3 the control arm vs an extended continuation phase regimen 2EHRZ3 7 RH3 in the treatment of pulmonary and extrapulmonary TB in the HIV positive patients
2 To study the relationship between stage of HIV disease and response to anti-TB treatment
3 To study recurrences and their nature relapsere-infection in detail by using RFLP analysis
Study DesignIt is a two armed prospective randomized open label controlled clinical trial with stratified random allocation based on CD4 count and sputum smear grade
All enrolled patients will be treated according to the RNTCP guidelines during the intensive phase In the continuation phase Cat I patients will be stratified by CD4 counts and by smear grade and randomly allocated either to the standard RNTCP regimen or to an alternative extended regimen 2EHRZ34RH3 or 2EHRZ37RH3
Detailed Description:
All HIV positive patients seeking care at one of the study centers above the age of 15 years not suffering from a serious illness non-pregnant and diagnosed with TB will be briefly explained the treatment trialPatients willing to participate in the trial will be asked to provide written consent Patients who refuse participation in the study will be managed according to the RNTCP guidelines
All patients who provide written consent to participate in the treatment trial will be interviewed by a social worker using a standard questionnaire Patients on anti-retroviral drugs will be excluded from the study Blood samples will be collected from patients meeting initial eligibility criteria to test for laboratory eligibility criteria Laboratory investigations will include complete heamogramRenal function tests Liver function tests random blood sugar urine albumin and urine sugar Patients who fulfill laboratory criteria hemoglobin 70 gL granulocyte count 11 X 109L platelet count 100X 109L serum alanine amino transferase concentration 25 times the upper limit of normal serum creatinine concentration 11mg random blood sugar 140 mgdl will be enrolled in to the study
Randomization and Dosing
All patients enrolled into the treatment trial will receive supervised directly observed treatment during the intensive phase At treatment initiation each patient will be counseled about the importance of treatment regularity While patients are undergoing intensive phase treatment they will be randomized either to the standard regimen or to the extended regimen as soon as CD4 results are available Randomization will be done according to a permuted block scheme in blocks of four stratified by CD4 counts 200 and 200 and by smear grade 0 1 2 or 3 The treatment assignment list will be generated before the start of trial and sequentially numbered sealed envelopes containing the treatment assigned will be prepared independently
The treatment regimens in each arm of the trial will be as follows
Category I RNTCP regimen 2EHRZ34RH3 Trial regimen 2EHRZ37RH3 Category II RNTCP regimen 2SEHRZ31EHRZ35EHR3 Category III RNTCP regimen 2HRZ34RH3 All anti-TB drugs will be administered as per the RNTCP strategy of DOTS Patients residing in Chennai and Madurai will attend the respective centers sub-centers three times a week for the intensive phase of treatment first twothree months and then once a week during the continuation phase four to seven months Dosages will be as per RNTCP manual and may be modified if the patient is extremely debilitated weight 30 kg Patients in all treatment arms will receive 10 mg of Pyridoxine on treatment days and Co-trimoxazole DS 1 tablet daily
During chemotherapy patients will be called to the clinic for monthly clinical evaluation During follow-up visits at the clinic monthly up to 24 months every 3 months after that patients will be thoroughly evaluated for likely drug toxicity and the information on adverse effects will be recorded on a standardized toxicity chart
Compliance with therapy will be measured by checking treatment cards DOTS provider notebooks and empty drug packets Additionally spot urine examination will be performed to check for acetyl isoniazid and rifampicin levels at each monthly
Statistical analysis
The intention-to-treat approach will be used for analyzing the data for primary and secondary end points Annual interim analyses will be done to ensure timely identification of any significant risks or benefits to patients
Comparisons of categorical variables will be done by chi-square test and Fishers exact test Continuous variables will be compared by t test or by Wilcoxons rank sum test Survival estimates will be made by the Kaplan-Meier method Comparison of Kaplan-Meier survival curves will be made with the log-rank test Multivariate analyses will be performed using Coxs proportional Hazards model
All patients who provide written consent to participate in the treatment trial will be interviewed by a social worker using a standard questionnaire Patients on anti-retroviral drugs will be excluded from the study Blood samples will be collected from patients meeting initial eligibility criteria to test for laboratory eligibility criteria Laboratory investigations will include complete heamogramRenal function tests Liver function tests random blood sugar urine albumin and urine sugar Patients who fulfill laboratory criteria hemoglobin 70 gL granulocyte count 11 X 109L platelet count 100X 109L serum alanine amino transferase concentration 25 times the upper limit of normal serum creatinine concentration 11mg random blood sugar 140 mgdl will be enrolled in to the study
Randomization and Dosing
All patients enrolled into the treatment trial will receive supervised directly observed treatment during the intensive phase At treatment initiation each patient will be counseled about the importance of treatment regularity While patients are undergoing intensive phase treatment they will be randomized either to the standard regimen or to the extended regimen as soon as CD4 results are available Randomization will be done according to a permuted block scheme in blocks of four stratified by CD4 counts 200 and 200 and by smear grade 0 1 2 or 3 The treatment assignment list will be generated before the start of trial and sequentially numbered sealed envelopes containing the treatment assigned will be prepared independently
The treatment regimens in each arm of the trial will be as follows
Category I RNTCP regimen 2EHRZ34RH3 Trial regimen 2EHRZ37RH3 Category II RNTCP regimen 2SEHRZ31EHRZ35EHR3 Category III RNTCP regimen 2HRZ34RH3 All anti-TB drugs will be administered as per the RNTCP strategy of DOTS Patients residing in Chennai and Madurai will attend the respective centers sub-centers three times a week for the intensive phase of treatment first twothree months and then once a week during the continuation phase four to seven months Dosages will be as per RNTCP manual and may be modified if the patient is extremely debilitated weight 30 kg Patients in all treatment arms will receive 10 mg of Pyridoxine on treatment days and Co-trimoxazole DS 1 tablet daily
During chemotherapy patients will be called to the clinic for monthly clinical evaluation During follow-up visits at the clinic monthly up to 24 months every 3 months after that patients will be thoroughly evaluated for likely drug toxicity and the information on adverse effects will be recorded on a standardized toxicity chart
Compliance with therapy will be measured by checking treatment cards DOTS provider notebooks and empty drug packets Additionally spot urine examination will be performed to check for acetyl isoniazid and rifampicin levels at each monthly
Statistical analysis
The intention-to-treat approach will be used for analyzing the data for primary and secondary end points Annual interim analyses will be done to ensure timely identification of any significant risks or benefits to patients
Comparisons of categorical variables will be done by chi-square test and Fishers exact test Continuous variables will be compared by t test or by Wilcoxons rank sum test Survival estimates will be made by the Kaplan-Meier method Comparison of Kaplan-Meier survival curves will be made with the log-rank test Multivariate analyses will be performed using Coxs proportional Hazards model
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None