Pirfenidone for Subglottic Stenosis

Idiopathic subglottic stenosis (iSGS) is a rare condition where scar tissue forms just below the vocal cords and in the upper windpipe, making the airway narrow. People with iSGS often feel short of breath, hear noisy breathing, and notice changes in their voice. Many need repeated operations and steroid injections to open the airway, but the narrowing usually comes back, so these treatments are not a cure.

Recent research from a Canadian iSGS registry and biobank has shown that this disease is driven by overactive scarring pathways, similar to those seen in idiopathic pulmonary fibrosis (IPF), a serious lung disease. Pirfenidone is an oral medication already approved for IPF that works by slowing down the cells and signals that cause scarring. Because the same scarring pathways appear to be active in iSGS, pirfenidone may be able to slow or reduce the build-up of scar tissue in the airway.

In this study, adults with iSGS will be randomly assigned (like flipping a coin) to receive either pirfenidone or a placebo (a look-alike pill with no active drug) for 52 weeks, in addition to their usual intralesional steroid injections. The pirfenidone dose will be increased gradually over the first two weeks up to a regular dose taken three times a day with food, which is the same schedule used in patients with IPF. Participants and their doctors will not know which treatment they are getting until the end of the study, unless this needs to be revealed for safety reasons.

The main goal of this trial is to find out whether people with iSGS can stay on pirfenidone for one year, and how often they have moderate or more serious side effects compared with placebo. The study team will watch closely for side effects such as stomach upset, skin rash or sensitivity to sunlight, tiredness, and changes in liver blood tests. The study will also show whether a larger trial is possible, by measuring how many eligible patients agree to take part and how many complete the year of treatment. The team will also look for early signs that pirfenidone may help, such as a longer time until the next airway surgery, better breathing (peak flow) measurements, and improvements in breathlessness and voice related quality of life scores.

Forty four participants will take part at two hospitals, one in London and one in Toronto, Ontario. Each participant will be followed for up to two years: one year on study medication and one year of follow up after treatment. This study may not directly help every person who takes part, but the results will show whether pirfenidone is tolerable in iSGS and will provide the information needed to plan a larger trial testing whether it could become the first medication to slow this scarring airway disease.