Clofazimine improves clinical outcomes in multidrug-resistant tuberculosis: a randomized controlled trial

Abstract Background: Adverse drug reactions (ADRs) frequently occur in patients using second-line anti-tuberculosis medicine for treatment of multidrug resistant tuberculosis (MDR-TB). ADRs contribute to treatment interruptions which can compromise treatment response and risk acquired drug resistance to critical newer drugs such as bedaquiline, while severe ADRs carry considerable morbidity and mortality . N-acetylcysteine (NAC) has shown promise in reducing ADRs for medications related to TB in case series or randomized controlled trials in other medical conditions. We therefore designed a pilot clinical trial to study the protective effect of NAC among people treated for MDR-TB with second-line anti-TB medications. Methods: This is a phase 2b randomized open label clinical trial with 3 treatment arms including a control arm , an interventional arm of NAC 900mg daily , and an interventional arm of NAC 900mg twice-daily administered during the intensive phase of MDR-TB treatment. Patients initiating MDR-TB treatment will be enrolled at Kibong’oto National Center of Excellence for MDR-TB in the Kilimanjaro region of Tanzania . The minimum anticipated sample size is 66 ; with 22 participants in each arm. ADR monitoring will be performed at baseline and daily follow-up over 24 weeks including blood and urine specimen collection for hepatic and renal function and electrolyte abnormalities, and electrocardiogram. Sputum will be collected at baseline and monthly thereafter and cultured for mycobacteria as well as assayed for other molecular targets of Mycobacterium tuberculosis . Adverse drug events will be analysed over time using mixed effect models. Mean differences between arms in change of the ADRs from baseline (with 95% confidence intervals) will be derived from the fitted model. Discussion: Given that NAC promotes synthesis of glutathione, an intracellular antioxidant that combats the impact of oxidative stress , it may protect against medication induced oxidative damage in organs such as liver, pancreas, kidney and cells of the immune system. This randomized controlled trial will determine if NAC leads to fewer ADRs, and if this protection is dose dependent. Fewer ADRs among patients treated with MDR-TB may significantly improve treatment outcomes for multidrug regimens that necessitate prolonged treatment durations. Trial registration: PACTR202007736854169 Registered 03 July 2020 https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=12163

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Phase 2b open label randomized controlled trial to evaluate the efficacy, safety and tolerability of N-acetylcysteine in reducing adverse drug reactions among adults treated for multidrug-resistant tuberculosis in Tanzania. (Trial Acronym NAC Trial).

10.21203/rs.3.rs-154310/v1 ◽

2021 ◽

Author(s):

Stellah Mpagama

Keyword(s):

Controlled Trial ◽

Multidrug Resistant ◽

Second Line ◽

Drug Reactions ◽

Open Label ◽

Randomized Controlled ◽

Tb Treatment ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Mdr Tb

Abstract Background: Adverse drug reactions (ADRs) frequently occur in patients using second-line anti-tuberculosis medicine for treatment of multidrug resistant tuberculosis (MDR-TB). ADRs contribute to treatment interruptions which can compromise treatment response and risk acquired drug resistance to critical newer drugs such as bedaquiline, while severe ADRs carry considerable morbidity and mortality. N-acetylcysteine (NAC) has shown promise in reducing ADRs for medications related to TB in case series or randomized controlled trials in other medical conditions. We therefore designed a pilot clinical trial to study the protective effect of NAC among people treated for MDR-TB with second-line anti-TB medications. Methods: This is a phase 2b randomized open label clinical trial with 3 treatment arms including a control arm, an interventional arm of NAC 900mg daily, and an interventional arm of NAC 900mg twice-daily administered during the intensive phase of MDR-TB treatment. Patients initiating MDR-TB treatment will be enrolled at Kibong’oto National Center of Excellence for MDR-TB in the Kilimanjaro region of Tanzania. The minimum anticipated sample size is 66; with 22 participants in each arm. ADR monitoring will be performed at baseline and regular follow-up over 24 weeks including blood and urine specimen collection for hepatic and renal function and electrolyte abnormalities, electrocardiogram and hearing function by pure tone audiometry. Sputum will be collected at baseline and monthly thereafter and cultured for mycobacteria as well as assayed for other molecular targets of Mycobacterium tuberculosis. Adverse drug events will be analyzed over time using mixed effect models. Mean differences between arms in change of the ADRs from baseline (with 95% confidence intervals) will be derived from the fitted model.Discussion: Given that NAC promotes synthesis of glutathione, an intracellular antioxidant that combats the impact of oxidative stress, it may protect against medication induced oxidative damage in organs such as liver, pancreas, kidney and cells of the immune system. This randomized controlled trial will determine if NAC leads to fewer ADRs, and if this protection is dose dependent. Fewer ADRs among patients treated with MDR-TB may significantly improve treatment outcomes for multidrug regimens that necessitate prolonged treatment durations.Trial registration: PACTR202007736854169

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Faculty Opinions recommendation of Use of hyaluronan in the selection of sperm for intracytoplasmic sperm injection (ICSI): significant improvement in clinical outcomes--multicenter, double-blinded and randomized controlled trial.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717969267.793470623 ◽

2013 ◽

Author(s):

Fatma F Verit

Keyword(s):

Randomized Controlled Trial ◽

Clinical Outcomes ◽

Intracytoplasmic Sperm Injection ◽

Controlled Trial ◽

Randomized Controlled ◽

Double Blinded ◽

Selection Of

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Clinical outcomes of adjunctive indocyanine green-diode lasers therapy for treating refractory periodontitis: A randomized controlled trial with in vitro assessment

Journal of the Formosan Medical Association ◽

10.1016/j.jfma.2019.08.021 ◽

2020 ◽

Vol 119 (2) ◽

pp. 652-659 ◽

Cited By ~ 2

Author(s):

Chun-Pin Chiang ◽

Olivia Hsieh ◽

Wei-Chiu Tai ◽

Yi-Jane Chen ◽

Po-Chun Chang

Keyword(s):

Randomized Controlled Trial ◽

Indocyanine Green ◽

Clinical Outcomes ◽

Controlled Trial ◽

Diode Lasers ◽

Randomized Controlled ◽

In Vitro Assessment

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Full versus Trophic Feeds in Critically Ill Adults with High and Low Nutritional Risk Scores: A Randomized Controlled Trial

Nutrients ◽

10.3390/nu12113518 ◽

2020 ◽

Vol 12 (11) ◽

pp. 3518

Author(s):

Chen-Yu Wang ◽

Pin-Kuei Fu ◽

Wen-Cheng Chao ◽

Wei-Ning Wang ◽

Chao-Hsiu Chen ◽

...

Keyword(s):

Randomized Controlled Trial ◽

Hospital Stay ◽

Clinical Outcomes ◽

Critically Ill ◽

Critically Ill Patients ◽

Controlled Trial ◽

Risk Scores ◽

Nutrition Risk ◽

Randomized Controlled ◽

Trophic Feeding

Although energy intake might be associated with clinical outcomes in critically ill patients, it remains unclear whether full or trophic feeding is suitable for critically ill patients with high or low nutrition risk. We conducted a prospective study to determine which feeding energy intakes were associated with clinical outcomes in critically ill patients with high or low nutrition risk. This was an investigator-initiated, single center, single blind, randomized controlled trial. Critically ill patients were allocated to either high or low nutrition risk based on their Nutrition Risk in the Critically Ill score, and then randomized to receive either the full or the trophic feeding. The feeding procedure was administered for six days. No significant differences were observed in hospital, 14-day and 28-day mortalities, the length of ventilator dependency, or ICU and hospital stay among the four groups. There were no associations between energy and protein intakes and hospital, 14-day and 28-day mortalities in any of the four groups. However, protein intake was positively associated with the length of hospital stay and ventilator dependency in patients with low nutrition risk receiving trophic feeding. Full or trophic feeding in critically ill patients showed no associations with clinical outcomes, regardless of nutrition risk.

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