NAC Combo Raises Death Risk in Pulmonary Fibrosis Study

observational-study PMID: 22607134

Quick Summary: A study found that combining N-acetylcysteine (NAC) with prednisone and azathioprine increased the risk of death and hospitalization in people with a lung condition called idiopathic pulmonary fibrosis (IPF). The study was stopped early because of these safety concerns.

What The Research Found

Researchers studied a combination of drugs, including NAC, to treat IPF. They found that people taking this combination were more likely to die or need to go to the hospital compared to those who didn't. The study was stopped early because the combination was causing harm.

Study Details

Who was studied: People with mild to moderate idiopathic pulmonary fibrosis (IPF).

How long: The study was cut short, but the combination group was followed for about 32 weeks.

What they took: The study used a combination of prednisone, azathioprine, and NAC. The exact doses of each drug are not specified in the provided study summary.

What This Means For You

If you have IPF, this study shows that the combination of prednisone, azathioprine, and NAC is not safe and should not be used. This study does not tell us anything about whether NAC alone is helpful or harmful. Talk to your doctor about the best treatment options for you.

Study Limitations

The study was stopped early, so we don't have long-term results.

The study only looked at a specific combination of drugs, not NAC by itself.

The study only included people with mild to moderate IPF.

Key Findings

The study demonstrated significantly increased mortality and hospitalization risks with the prednisone-azathioprine-NAC combination versus placebo in idiopathic pulmonary fibrosis (IPF) patients. Death rates were 8 vs. 1 (P=0.01), and hospitalizations were 23 vs. 7 (P<0.001). No clinical or physiological benefits were observed for the combination therapy, leading to early trial termination for this arm. The study provides evidence against using this specific triple-drug regimen in IPF.

Study Design

This was a randomized, double-blind, placebo-controlled trial (NCT00650091) funded by the National Heart, Lung, and Blood Institute. Patients with mild-to-moderate IPF were assigned 1:1:1 to combination therapy (prednisone/azathioprine/NAC), NAC monotherapy, or placebo. At the planned interim analysis (50% data collection), 77 patients in the combination group and 78 in placebo were analyzed. The primary outcome was longitudinal forced vital capacity change over 60 weeks, but the combination arm was terminated at mean 32 weeks due to safety concerns.

Dosage & Administration

The provided study summary does not specify exact dosages for prednisone, azathioprine, or NAC in the combination regimen. All interventions were administered orally as part of the triple-therapy protocol, with NAC included as a fixed component of the combination arm. Dosing details for the NAC monotherapy arm were also not reported in this publication.

Results & Efficacy

Combination therapy showed statistically significant harm versus placebo: mortality risk increased 8-fold (8 deaths vs. 1; P=0.01) and hospitalizations tripled (23 vs. 7; P<0.001). No efficacy benefit was observed for the primary outcome (forced vital capacity change) or secondary clinical endpoints. The hazard ratio for death/hospitalization was not calculable due to early termination, but the absolute risk differences were clinically severe. The data monitoring board concluded the combination provided "no evidence of physiological or clinical benefit."

Limitations

Early termination after 32 weeks (vs. planned 60) limited long-term conclusions. Only 50% of intended data was collected, reducing statistical power. Results apply specifically to mild-to-moderate IPF and may not generalize to advanced disease. Critically, NAC monotherapy outcomes versus placebo were not reported in this publication, leaving NAC's standalone efficacy unaddressed. The study design couldn't isolate NAC's contribution to the observed harms.

Clinical Relevance

This study establishes that the prednisone-azathioprine-NAC combination is dangerous for IPF patients and should be avoided. The 8:1 death ratio and significant hospitalization increase indicate life-threatening risks. However, these findings do not apply to NAC alone—the monotherapy arm results were excluded from this report. Clinicians should discontinue this specific triple regimen immediately, but NAC's standalone safety/efficacy in IPF requires separate evaluation. Supplement users with IPF must consult physicians before using NAC, as context (monotherapy vs. combinations) critically determines risk.