Dataset Information

Prednisone, azathioprine, and N-acetylcysteine for pulmonary fibrosis.

ABSTRACT:

Background

A combination of prednisone, azathioprine, and N-acetylcysteine (NAC) has been widely used as a treatment for idiopathic pulmonary fibrosis. The safety and efficacy of this three-drug regimen is unknown.

Methods

In this randomized, double-blind, placebo-controlled trial, we assigned patients with idiopathic pulmonary fibrosis who had mild-to-moderate lung-function impairment to one of three groups -- receiving a combination of prednisone, azathioprine, and NAC (combination therapy), NAC alone, or placebo -- in a 1:1:1 ratio. The primary outcome was the change in longitudinal measurements of forced vital capacity during a 60-week treatment period.

Results

When approximately 50% of data had been collected (with 77 patients in the combination-therapy group and 78 in the placebo group), a planned interim analysis revealed that patients in the combination-therapy group, as compared with the placebo group, had an increased rate of death (8 vs. 1, P=0.01) and hospitalization (23 vs. 7, P<0.001). These observations, coupled with no evidence of physiological or clinical benefit for combination therapy, prompted the independent data and safety monitoring board to recommend termination of the combination-therapy group at a mean follow-up of 32 weeks. Data from the ongoing comparison of the NAC-only group and the placebo group are not reported here.

Conclusions

Increased risks of death and hospitalization were observed in patients with idiopathic pulmonary fibrosis who were treated with a combination of prednisone, azathioprine, and NAC, as compared with placebo. These findings provide evidence against the use of this combination in such patients. (Funded by the National Heart, Lung, and Blood Institute and the Cowlin Family Fund; ClinicalTrials.gov number, NCT00650091.).

SUBMITTER: Idiopathic Pulmonary Fibrosis Clinical Research Network

PROVIDER: S-EPMC3422642 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature

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Publications

Prednisone, azathioprine, and N-acetylcysteine for pulmonary fibrosis.

Raghu Ganesh G Anstrom Kevin J KJ King Talmadge E TE Lasky Joseph A JA Martinez Fernando J FJ

The New England journal of medicine 20120520 21

<h4>Background</h4>A combination of prednisone, azathioprine, and N-acetylcysteine (NAC) has been widely used as a treatment for idiopathic pulmonary fibrosis. The safety and efficacy of this three-drug regimen is unknown.<h4>Methods</h4>In this randomized, double-blind, placebo-controlled trial, we assigned patients with idiopathic pulmonary fibrosis who had mild-to-moderate lung-function impairment to one of three groups -- receiving a combination of prednisone, azathioprine, and NAC (combinat ...[more]

PMID: 22607134

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Project description:BackgroundNumerous studies have demonstrated the potential of pirfenidone to enhance the prognosis of patients afflicted with idiopathic pulmonary fibrosis (IPF). Although N-acetylcysteine (NAC) is utilized as an antioxidant in IPF treatment, the combination of NAC and pirfenidone has produced inconsistent outcomes in certain studies. To assess the clinical effectiveness and safety of NAC plus pirfenidone (designated as the treatment group) versus pirfenidone monotherapy (designated as the control group), we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs).MethodsRCTs of NAC plus pirfenidone were reviewed searching from databases and networks of unpublished and published studies in any language. Using pair-wise meta-analysis, changes in pulmonary function test (PFT) parameters and safety were evaluated.ResultsTwo independent reviewers selected and obtained data from 5 RCTs (n = 398), comprising 1 study from Japan, 1 from Europe, and 3 from China. NAS plus pirfenidone as compared to pirfenidone monotherapy for IPF may not reduce the incidence of skin effects(RR 1.26 [95%CI 0.64 to 2.45]) and mortality(RR 0.35 [95%CI 0.07 to 1.68])(both moderate certainty). NAS plus pirfenidone as compared to pirfenidone monotherapy for IPF may not reduce the incidence of at least one side effects(RR 1.00 [95%CI 0.84 to 1.19]; low certainty),severe side effects(RR 0.67 [95%CI 0.30 to 1.47]; low certainty) and gastrointestinal effects(RR 0.67 [95%CI 0.41 to 1.09]; low certainty) with possibly no effect in Δ%DLco(SMD -0.17 [95%CI -0.15 to 0.48]; low certainty). Meanwhile, the effect of NAS plus pirfenidone as compared to pirfenidone monotherapy on ΔFVC(SMD 0.18 [95%CI -0.68 to 1.05]), Δ%FVC(SMD -2.62 [95%CI -5.82 to 0.59]) and Δ6MWT(SMD -0.35 [95%CI -0.98 to 0.28]) is uncertain(extremely low certainty).ConclusionModerate certainty evidence suggests that NAS plus pirfenidone, compared to pirfenidone monotherapy for IPF, does not reduce the incidence of skin effects and mortality.

Project description:BackgroundIdiopathic pulmonary fibrosis (IPF) is a major global health problem. The prevalence of the disease appears to be increasing. There is no curative therapy for IPF except lung transplantation. Chinese herbal medicines (CHMs) are showing promise for treatment of IPF. However, their effectiveness and safety are still unclear and deserve further investigation. The aim of this systematic review is to access the efficacy and safety of CHMs in treating IPF.MethodsThe protocol of this review is registered at PROSPERO. We searched seven main databases for randomized clinical trials (RCTs) on CHMs for IPF from their inception to June 4, 2018. The methodological quality of RCTs was assessed using the Cochrane risk of bias tool. All trials included were analyzed according to the criteria of the Cochrane Handbook. Review Manager 5.3, R-3.5.2 software, and Grade pro GDT web solution were used for data synthesis and analysis.ResultsThirteen randomized clinical trials enrolling 733 patients were included. All trials included had clear outcome indicators. The methodological quality of included trials was generally "poor." Few trials reported methods of randomization. One trial on Xuefu-zhuyu capsule assessed rate of acute exacerbation and mortality after treatment for 72 weeks and found no statistically significant difference between two groups. This meta-analysis demonstrated a significant improvement in QOL of IPF patients when CHMs was applied or combined with conventional medicine treatment. 6MWT was significantly improved in IPF patients after using CHMs or combined with conventional medicine treatment. CHMs treatment also had a certain improvement in TLC and DLCO, but the effect on FVC was not significant. Besides, CHMs failed to provide benefits in terms of PaO2. The reported adverse events were not obvious and severe.ConclusionsSome CHMs seem effective and safe as alternative remedies for patients with IPF, suggesting that further study of CHMs in the treatment of IPF is warranted. Although this systematic review suggests that CHMs may have positive effect on quality of life, 6-minute walk test distance, and lung function (TLC, DLOC%) and seem to be relatively safe during the course of treatment, the results must be treated with great caution because of the methodological flaws of the included trials. Long-term and high-quality trials are needed in the future to provide clear evidence for the use of CHMs.

Dataset Information

Prednisone, azathioprine, and N-acetylcysteine for pulmonary fibrosis.

Background

Methods

Results

Conclusions

Publications

Prednisone, azathioprine, and N-acetylcysteine for pulmonary fibrosis.

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