Dataset Information

Daily vs Intermittent Antituberculosis Therapy for Pulmonary Tuberculosis in Patients With HIV: A Randomized Clinical Trial.

ABSTRACT: Importance:The benefit of daily over thrice-weekly antituberculosis therapy among HIV-positive patients with pulmonary tuberculosis (TB) who are receiving antiretroviral therapy remains unproven. Objective:To compare the efficacy and safety of daily, part-daily, and intermittent antituberculosis therapy regimens in the treatment of HIV-associated pulmonary TB. Design, Setting, and Participants:This open-label, randomized clinical trial was conducted by the National Institute for Research in Tuberculosis, south India. Adults infected with HIV with newly diagnosed, culture-positive, pulmonary TB were enrolled between September 14, 2009, and January 18, 2016. Interventions:Patients were randomized to daily, part-daily, and intermittent antituberculosis therapy regimens, stratified by baseline CD4 lymphocyte count and sputum smear grade. Antiretroviral therapy was initiated as per national guidelines. Clinical and sputum microbiological examinations of patients were performed monthly until 18 months after randomization. Adverse events were recorded using standard criteria. Main Outcomes and Measures:The primary outcome was favorable response, defined as treatment completion with all available sputum cultures negative for Mycobacterium tuberculosis during the last 2 months of treatment. Unfavorable responses included treatment failures, dropouts, deaths, and toxic effects among regimens. Results:Of 331 patients (251 [76%] male; mean [SD] age, 39 [9] years; mean [SD] HIV viral load, 4.9 [1.2] log10 copies/mL; and median [interquartile range] CD4 lymphocyte count, 138 [69-248] cells/?L), favorable responses were experienced by 91% (89 of 98), 80% (77 of 96), and 77% (75 of 98) in the daily, part-daily, and intermittent regimens, respectively. With the difference in outcome between daily and intermittent regimens crossing the O'Brien-Fleming group sequential boundaries and acquired rifampicin resistance emergence (n?=?4) confined to the intermittent group, the data safety monitoring committee halted the study. A total of 18 patients died and 18 patients dropped out during the treatment period in the 3 regimens. Six, 4, and 6 patients in the daily, part-daily, and intermittent regimens, respectively, had TB recurrence. Conclusions and Relevance:Among HIV-positive patients with pulmonary TB receiving antiretroviral therapy, a daily anti-TB regimen proved superior to a thrice-weekly regimen in terms of efficacy and emergence of rifampicin resistance. Trial Registration:clinicaltrials.gov Identifier: NCT00933790.

SUBMITTER: Gopalan N

PROVIDER: S-EPMC5885164 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Daily vs Intermittent Antituberculosis Therapy for Pulmonary Tuberculosis in Patients With HIV: A Randomized Clinical Trial.

Gopalan Narendran N Santhanakrishnan Ramesh Kumar RK Palaniappan Alangudi Natarajan AN Menon Pradeep Aravindan PA Lakshman Sekar S Chandrasekaran Padmapriyadarsini P Sivaramakrishnan Gomathi Narayan GN Reddy Devarajulu D Kannabiran Bhavani Perumal BP Agiboth Hemanth Kumar Kupparam HKK Krishnamoorthy Vijay V Rathinam Sridhar S Chockalingam Chandrasekar C Manoharan Tamizhselvan T Ayyamperumal MahilMaran M Jayanthi Nalini N Satagopan Kumar K Narayanan Ravichandran R Krishnaraja Raja R Sathiyavelu Sekar S Kesavamurthy Bhanu B Suresh Chandra C Selvachitiram Murugesan M Arasan Gunasundari G Susaimuthu Stella S Rathinam Prabhakaran P Angamuthu Prabhakar P Jayabal Lavanya L Murali Lakshmi L Ramachandran Ranjani R Tripathy Srikanth Prasad SP Swaminathan Soumya S

JAMA internal medicine 20180401 4

<h4>Importance</h4>The benefit of daily over thrice-weekly antituberculosis therapy among HIV-positive patients with pulmonary tuberculosis (TB) who are receiving antiretroviral therapy remains unproven.<h4>Objective</h4>To compare the efficacy and safety of daily, part-daily, and intermittent antituberculosis therapy regimens in the treatment of HIV-associated pulmonary TB.<h4>Design, setting, and participants</h4>This open-label, randomized clinical trial was conducted by the National Institut ...[more]

PMID: 29507938

Similar Datasets

Project description:BACKGROUND:Daily sedative interruption and intermittent sedation are effective in abbreviating the time on mechanical ventilation. Whether one is superior to the other has not yet been determined. Our aim was to compare daily interruption and intermittent sedation during the mechanical ventilation period in a low nurse staffing ICU. METHODS:Adult patients expected to need mechanical ventilation for more than 24 hours were randomly assigned, in a single center, either to daily interruption of continuous sedative and opioid infusion or to intermittent sedation. In both cases, our goal was to maintain a Sedation Agitation Scale (SAS) level of 3 or 4; that is patients should be calm, easily arousable or awakened with verbal stimuli or gentle shaking. Primary outcome was ventilator-free days in 28 days. Secondary outcomes were ICU and hospital mortality, incidence of delirium, nurse workload, self-extubation and psychological distress six months after ICU discharge. RESULTS:A total of 60 patients were included. There were no differences in the ventilator-free days in 28 days between daily interruption and intermittent sedation (median: 24 versus 25 days, P?=?0.160). There were also no differences in ICU mortality (40 versus 23.3%, P?=?0.165), hospital mortality (43.3 versus 30%, P?=?0.284), incidence of delirium (30 versus 40%, P?=?0.472), self-extubation (3.3 versus 6.7%, P?=?0.514), and psychological stress six months after ICU discharge. Also, the nurse workload was not different between groups, but it was reduced on day 5 compared to day 1 in both groups (Nurse Activity Score (NAS) in the intermittent sedation group was 54 on day 1 versus 39 on day 5, P?<?0.001; NAS in daily interruption group was 53 on day 1 versus 38 on day 5, P?<?0.001). Fentanyl and midazolam total dosages per patient were higher in the daily interruption group. The tidal volume was higher in the intermittent sedation group during the first five days of ICU stay. CONCLUSIONS:There was no difference in the number of ventilator-free days in 28 days between both groups. Intermittent sedation was associated with lower sedative and opioid doses. TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT00824239.

Project description:IntroductionShorter duration of treatment for the management of drug-susceptible pulmonary tuberculosis (TB) would be a significant improvement in the care of patients suffering from the disease. Besides newer drugs and regimens, other modalities like host-directed therapy are also being suggested to reach this goal. This study's objective is to assess the efficacy and safety of metformin-containing anti-TB treatment (ATT) regimen in comparison to the standard 6-month ATT regimen in the treatment of patients with newly diagnosed sputum smear-positive drug-sensitive pulmonary TB.Methods and analysisWe are conducting a multicentric, randomised open-label controlled clinical trial to achieve the study objective. The intervention group will receive isoniazid (H), rifampicin (R), ethambutol (E) and pyrazinamide (Z) along with 1000 mg of daily metformin (Met) for the first 2 months while the control group will receive only HRZE. After 2 months, both the groups will receive HRE daily for 4 months. The primary endpoint is time to sputum culture conversion. Secondary endpoints will include time to detection of Mycobacterium tuberculosis in sputum, pharmacokinetics and pharmacogenomics of study drugs, drug-drug interactions, safety and tolerability of the various combinations and measurement of autophagy and immune responses in the study participants.Ethics and disseminationThe ethics committee of the participating institutes have approved the study. Results from this trial will contribute to evidence towards constructing a shorter, effective and safe regimen for patients with TB. The results will be shared widely with the National Programme managers, policymakers and stakeholders through open access publications, dissemination meetings, conference abstracts and policy briefs. This is expected to provide a new standard of care for drug-sensitive patients with pulmonary TB who will not only reduce the number of clinic visits and lost to follow-up of patients from treatment but also reduce the burden on the healthcare system.Trial registration numberCTRI/2018/01/011176; Pre-results.

Dataset Information

Daily vs Intermittent Antituberculosis Therapy for Pulmonary Tuberculosis in Patients With HIV: A Randomized Clinical Trial.

Publications

Daily vs Intermittent Antituberculosis Therapy for Pulmonary Tuberculosis in Patients With HIV: A Randomized Clinical Trial.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets