Recruitment to clinical trials is a key objective in the management of IPF. For phase 3 trials, the inclusion and exclusion criteria are stringent. It is not known if the natural history of IPF in patients eligible for clinical trials differs from that in non-eligible patients.
Aims To determine the natural history of IPF in patients eligible for phase 3 trials vs those not eligible
Methods Since 1/1/2002, all patients with IPF presenting to the Edinburgh Royal Infirmary lung fibrosis clinic have been recruited prospectively to a database. The diagnosis of IPF was made by multi-disciplinary consensus after integration of clinical, HRCT and pathological data, based on ATS/ERS criteria. Management and follow-up was by standardised protocol. IPF-directed therapy, including corticosteroids, azathioprine and anti-oxidants, was considered only in advanced disease, acute exacerbation or in those who exhibited pre-specified fall in lung function. Patients were grouped into those eligible for phase 3 clinical trials and those ineligible, based on the major inclusion/exclusion criteria used in a recently published study (CAPACITY, Lancet 2011 377;1760–1769).
Results Of 199 consecutively presenting patients with IPF, 61 (31%) were eligible for a phase 3 trial. The proportion of males in the eligible and ineligible groups was similar, but eligible patients were younger (68 vs 74 yrs, p<0.0001), comprised fewer individuals with >20 pack/year smoking history (50% vs 65%, p=0.057), had lower % predicted VC (82.6 vs 95.8 p=0.0003) and higher % predicted TLCO (56.6 vs 51.9, p=0.07). Eligible patients had less % emphysema on HRCT scoring compared to non-eligible patients (0.74% vs 6% p<0.0001). The 3yr-survival of eligible and ineligible patients were not significantly different (Abstract S137 figure 1 74% vs 63%, p=0.3). Event-free survival, defined as time to death or =10% fall in VC or =15% fall in TLCO or acute exacerbation of IPF or hospital admission with respiratory illness, was not significantly different between eligible and ineligible groups, such that in both groups 40% and 60% experienced a progression-defining event by 12 -and 24-months respectively.
Conclusions Trial ineligible patients are demographically and phenotypically different from eligible patients, but have identical mortality and progression-free survival. These data have important implications for translation of trial data to clinical practice and for IPF trial design.
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