A much anticipated Phase 2 study looking at gastroesophageal reflux surgery in patients with IPF that failed to meet its primary endpoint illustrates that the selection of a trial endpoint is critical, an expert says.
Published in Lancet Respiratory the WRAP-IPF study randomly assigned 29 patients with IPF and abnormal gastro-oesophageal reflux (GER) to receive laparoscopic anti-reflux surgery and 29 to receive usual medical care.
An intention to treat analysis revealed that the primary endpoint of adjusted change in FVC from randomisation to 48 weeks did not meet statistical significance (0.05L, 95% CI-0.15 to 0.05 in the surgery group vs -0.13L, -0.23 to 0.02 in the no surgery group).
The secondary endpoints of acute exacerbation, respiratory-related hospitalisation, and death was less common in the surgery group but also did not reach statistical significance.
The authors led by Ganesh Raghu from the Department of Medicine, University of Washington, Seattle, said that the trial was underpowered for the observed effect size, with about 400 patients required to achieve 90% power.
“We believe the non-significant numerical differences in the primary and secondary endpoints warrant further study of laparoscopic anti-reflux surgery as treatment for patients with IPF….patients with IPF and abnormal acid GER might be an important subgroup of this disease and further research is needed to discover whether they could benefit from anti-reflux surgery to prevent microaspiration and further injury to the lung,” they said.
Writing in an accompanying editorial Kerri A Johannson from the University of Calgary said that in light of the data IPF patients should not [yet] be referred for surgery. Laparascopic surgery was an invasive procedure that was not without risks, complications and costs. More data was also needed to show that abnormal GER was pathogenic in the development and progression of IPF.
“There may be many ways to douse a fire, but the most critical step is cutting off its fuel supply. If abnormal GER does indeed fan the flames of epithelial injury and aberrant wound repair in the IPF lung, then the optimal intervention should definitively eliminate that GER,” she wrote.
“Whether a larger, adequately powered follow-up trial can feasibly be conducted is still unknown, but the current findings suggest that further study is warranted,” she concluded.