Ignite Creation Date:
2024-05-05 @ 6:32 PM
Last Modification Date:
2024-10-26 @ 9:34 AM
Study NCT ID:
NCT00495651
Status:
COMPLETED
Last Update Posted:
2015-06-03
First Post:
2007-07-02
Brief Title:
Early Antiretroviral Treatment andor Early Isoniazid Prophylaxis Against Tuberculosis in HIV-infected Adults ANRS 12136 TEMPRANO
Sponsor:
French National Agency for Research on AIDS and Viral Hepatitis
Organization:
ANRS Emerging Infectious Diseases
Study Overview
Official Title:
Benefits and Risks of Early Antiretroviral Therapy in HIV-infected Adults in Abidjan Côte dIvoire Randomized Controlled Trial ANRS 12136 TEMPRANO
Status:
COMPLETED
Status Verified Date:
2015-06
Last Known Status:
None
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:
TEMPRANO
Brief Summary:
The Temprano trial is based on the following assumptions
ART initiation at CD4 counts 800mm3 could significantly reduce the probability of severe HIV-related morbidity or death in the medium term
Tuberculosis and tuberculosis-related deaths are likely to represent a considerable proportion of morbidity and mortality among HIV-infected patients with high CD4 counts in sub-Saharan Africa Therefore 6-month Isoniazide Prophylaxis for Tuberculosis IPT and early ART could enhance each others efficacy
ART initiation at CD4 counts 800mm3 could significantly reduce the probability of severe HIV-related morbidity or death in the medium term
Tuberculosis and tuberculosis-related deaths are likely to represent a considerable proportion of morbidity and mortality among HIV-infected patients with high CD4 counts in sub-Saharan Africa Therefore 6-month Isoniazide Prophylaxis for Tuberculosis IPT and early ART could enhance each others efficacy
Detailed Description:
The main individual benefit of very early ART initiation is likely a reduction in early severe AIDS-defining and non-AIDS-defining morbidity While the diseases that might justify earlier initiation in high-income countries are generally non-infectious non-AIDS-defining malignancies renal diseases and cardiovascular diseases the leading cause of early severe AIDS-defining morbidity in sub-Saharan Africa is tuberculosis and the main causes of severe non-AIDS-defining morbidity are non-invasive bacterial diseases As a result of poor access to diagnosis and care some HIV-infected people die from early infectious diseases before reaching current WHO criteria for starting ART
Although the Côte dIvoire National Tuberculosis Program PNLT does not authorize the use of prophylaxis against tuberculosis it has allowed the Temprano trial to provide a six-month course of isoniazid INH prophylaxis to half of the study subjects This will allow us to i put early ART in perspective with a early 6-month INH prophylaxis use in a setting where tuberculosis is the first cause of severe HIV-associated morbidity and ii to describe and assess the feasibility of a six-month course of INH prophylaxis among patients with high CD4 counts
Some drug toxicities are immediate but reversible If early ART is compared to no ART in the short term these toxicities may demonstrate erroneously that early ART is unfavorable The risks and benefits of early ART initiation should therefore be evaluated over the long term In the Temprano trial we will i follow patients for at least 30 months and analyze the primary outcome at 30 months ii follow some study subjects for 80 months and evaluate the evolution of the ART efficacy toxicity ratio from month 30 to month 80 as a secondary endpoint to inform future policies if early ART is found to be beneficial at 30 months
Main objective To assess the benefits and risks of starting ART immediately andor to receive a 6-month IPT among HIV-infected adults with CD4 counts 800mm3 and no criteria for starting ART immediately according to the most recent WHO guidelines
Location Abidjan Côte dIvoire
Methods randomized 2x2 factorial superiority trial
Main inclusion criteria i HIV-1 or HIV-12 infection ii age 18 years iii nadir CD4 count 800mm3 and no criteria for starting ART immediately according to the most recent WHO guidelines and iv no active tuberculosis
Trial arms Arm I ART initiation according to WHO criteria at any time during follow-up Arm II INH prophylaxis 300 mgday for six months and ART initiation according to WHO criteria at any time during follow-up Arm III immediate ART initiation before reaching the WHO criteria Arm IV INH prophylaxis 300 mgday for six months and immediate ART initiation before reaching the WHO criteria
First-line ART regimens
Tenofovir emtricitabine efavirenz for all HIV-1-infected men and all HIV-1-infected women who meet the following requirements on effective contraception and no history of nevirapine use for the prevention of mother-to-child transmission of HIV PMTCT
Tenofovir emtricitabine lopinavir ritonavir for all HIV-12-infected patients and all women who do not use effective contraception or who have a history of nevirapine use for PMTCT
Primary endpoint Death all-cause AIDS-defining disease non-AIDS-defining malignancy or non-AIDS-defining invasive bacterial disease
Main secondary endpoint Grade 3 or 4 clinical event including renal and cardiovascular events or laboratory test result as defined by the ANRS classification system of drug-related adverse events
Final primary analysis It will be performed once the last patient has reached 30 months of follow-up Time-dependent analyses will compare the primary outcome i among patients initiating ART immediately arms III and IV versus patients initiating ART according to the WHO criteria arms I and II ii among patients who were prescribed a 6-months arms II and IV IPT versus those who were not arms I and III
Intermediate analysis on safety criteria
Toxicity all-cause mortality We have not planned to perform any intermediate analyses for this criterion If the number of observed deaths is higher than anticipated however the DSMB may decide to carry one out In this case we will adjust the alpha coefficient using the method suggested by Pocock to account for the large variety of available tests
Efficacy incidence of severe morbidity Intermediate analysis We have not planned any intermediate analyses for this criterion If the number of severe morbidity evens is higher than anticipated once all patients have reached 12 months of follow-up the DSMB may decide to carry one out In this case we will adjust the alpha coefficient using the method suggested by Haybittle-Peto to account for the large variety of available tests
Although the Côte dIvoire National Tuberculosis Program PNLT does not authorize the use of prophylaxis against tuberculosis it has allowed the Temprano trial to provide a six-month course of isoniazid INH prophylaxis to half of the study subjects This will allow us to i put early ART in perspective with a early 6-month INH prophylaxis use in a setting where tuberculosis is the first cause of severe HIV-associated morbidity and ii to describe and assess the feasibility of a six-month course of INH prophylaxis among patients with high CD4 counts
Some drug toxicities are immediate but reversible If early ART is compared to no ART in the short term these toxicities may demonstrate erroneously that early ART is unfavorable The risks and benefits of early ART initiation should therefore be evaluated over the long term In the Temprano trial we will i follow patients for at least 30 months and analyze the primary outcome at 30 months ii follow some study subjects for 80 months and evaluate the evolution of the ART efficacy toxicity ratio from month 30 to month 80 as a secondary endpoint to inform future policies if early ART is found to be beneficial at 30 months
Main objective To assess the benefits and risks of starting ART immediately andor to receive a 6-month IPT among HIV-infected adults with CD4 counts 800mm3 and no criteria for starting ART immediately according to the most recent WHO guidelines
Location Abidjan Côte dIvoire
Methods randomized 2x2 factorial superiority trial
Main inclusion criteria i HIV-1 or HIV-12 infection ii age 18 years iii nadir CD4 count 800mm3 and no criteria for starting ART immediately according to the most recent WHO guidelines and iv no active tuberculosis
Trial arms Arm I ART initiation according to WHO criteria at any time during follow-up Arm II INH prophylaxis 300 mgday for six months and ART initiation according to WHO criteria at any time during follow-up Arm III immediate ART initiation before reaching the WHO criteria Arm IV INH prophylaxis 300 mgday for six months and immediate ART initiation before reaching the WHO criteria
First-line ART regimens
Tenofovir emtricitabine efavirenz for all HIV-1-infected men and all HIV-1-infected women who meet the following requirements on effective contraception and no history of nevirapine use for the prevention of mother-to-child transmission of HIV PMTCT
Tenofovir emtricitabine lopinavir ritonavir for all HIV-12-infected patients and all women who do not use effective contraception or who have a history of nevirapine use for PMTCT
Primary endpoint Death all-cause AIDS-defining disease non-AIDS-defining malignancy or non-AIDS-defining invasive bacterial disease
Main secondary endpoint Grade 3 or 4 clinical event including renal and cardiovascular events or laboratory test result as defined by the ANRS classification system of drug-related adverse events
Final primary analysis It will be performed once the last patient has reached 30 months of follow-up Time-dependent analyses will compare the primary outcome i among patients initiating ART immediately arms III and IV versus patients initiating ART according to the WHO criteria arms I and II ii among patients who were prescribed a 6-months arms II and IV IPT versus those who were not arms I and III
Intermediate analysis on safety criteria
Toxicity all-cause mortality We have not planned to perform any intermediate analyses for this criterion If the number of observed deaths is higher than anticipated however the DSMB may decide to carry one out In this case we will adjust the alpha coefficient using the method suggested by Pocock to account for the large variety of available tests
Efficacy incidence of severe morbidity Intermediate analysis We have not planned any intermediate analyses for this criterion If the number of severe morbidity evens is higher than anticipated once all patients have reached 12 months of follow-up the DSMB may decide to carry one out In this case we will adjust the alpha coefficient using the method suggested by Haybittle-Peto to account for the large variety of available tests
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