Troesophageal reflux, ethnic background, gender, smoking history, and emphysema 25 on HRCT. Continuous subgroup aspects were splitNIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptN Engl J Med. Author manuscript; accessible in PMC 2014 November 29.Martinez et al.Pageinto two groups according to the median worth. Given the significant protocol modifications associated to the termination in the three-drug regimen, we analyzed the cohorts of patients randomized before versus following the clinical alert (`pre and post clinical alert’ subgroups) to explore the possibility of any variations amongst these subgroups. This comparison was not specified within the updated statistical analysis strategy. For subgroup analyses (PANTHER-IPF protocol, mGluR1 Activator Gene ID section 2.4), a conservative degree of 0.001 was applied for statistical significance.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptRESULTSBaseline Traits In between December 2009 and October 2011 (pre-alert) and between January 2012 and July 2012 (post-alert), 264 patients had been enrolled in to the study arms: 133 in the NAC and 131 within the placebo group (Figure 1). Involving October 2011 and January 2012 enrollment was suspended even though the protocol was amended and approved by the Steering NF-κB Inhibitor MedChemExpress Committee, DSMB, and nearby IRBs. The study groups had been nicely matched–the mean age for the population was 67 years, 22 from the individuals had been females and 96 have been white (Table 1). The imply % predicted FVC and DLCO have been 73 and 45 , respectively. The imply 6MWT distance was 373 meters. HRCT findings were adequate to diagnose definite UIP in 77 of instances. A total of 139/264 (52.six ) of participating subjects underwent surgical lung biopsy. Study Drug Adherence A total of 34 of 133 sufferers in the NAC group and 29 of 131 within the placebo group discontinued study medications (p=0.53). At 30-weeks, 93.three in the NAC arm and 91.7 within the placebo arm reported taking additional than 80 of the suggested doses of study drug. Similarly, at 60-weeks, 90.4 inside the NAC arm and 94.four within the placebo arm reported taking far more than 80 with the advised doses of study drug. Main Outcome Measure Making use of the worst-rank score evaluation, there had been no statistically significant variations in FVC predicted amongst the therapy groups at any on the time points (p=0.77, Table two, Figure 2A and Figure S1). There had been no statistically significant variations inside the major endpoint inside the predefined subgroups. Secondary Outcome Measures For the majority of pre-defined secondary endpoints there was no distinction among NAC and placebo (Table two), including DLco (Figure S3(a)). On the other hand, a trend favoring NAC in 6MWD (p=0.076; Figure S3(b)), EuroQoL Visual Analog Scale (p=0.069), improvement in SF-36 Mental Score (p=0.025) and ICECAP summary score (p=0.013) have been noted (Table 2). Over the 60-week remedy period there were no substantial variations in between NAC and placebo for mortality (six [4.9 ] vs. 3 [2.5 ] events, p=0.50) or acute exacerbation (three [2.three ] vs. three [2.three ] events, p0.99). Amongst other measures, there have been no statistically substantial variations between study groups for respiratory mortality, all-cause hospitalizations,N Engl J Med. Author manuscript; accessible in PMC 2014 November 29.Martinez et al.Pagerespiratory hospitalizations, or the proportion of patients experiencing disease progression (all-cause mortality or even a ten decline in FVC) (Table 3 and Figure S2(a )).NIH-PA Author Manuscript NIH-PA Author M.