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NCT02951429

Efficacy, Safety, and Tolerability Study of Pirfenidone in Combination With Sildenafil in Participants With Advanced Idiopathic Pulmonary Fibrosis (IPF) and Intermediate or High Probability of Group 3 Pulmonary Hypertension

Completed Phase 2 Results posted Last updated 12 November 2020
What this trial tests

Phase 2 trial testing Pirfenidone in Idiopathic Pulmonary Fibrosis in 177 participants. Completed in 22 August 2020.

Timeline
31 December 2016
Primary endpoint
26 September 2019
22 August 2020

Quick facts

Lead sponsorHoffmann-La Roche
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment177
Start date31 December 2016
Primary completion26 September 2019
Estimated completion22 August 2020
Sites56 locations across Italy, South Africa, Netherlands, Greece, Turkey (Türkiye), Belgium, Germany, Hungary

Drugs / interventions tested

Conditions studied

Sponsor

Hoffmann-La Roche — full company profile →

Who can join

Adults 40 to 80, any sex, with Idiopathic Pulmonary Fibrosis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants With Disease Progression, as Determined by Relevant Decline in 6 Minute Walk Distance (6MWD) of At Least (>=) 15 Percent (%) From Baseline, Respiratory-Related Non-Elective Hospitalization, or Death From Any Cause Primary · Baseline up to Week 52

Disease Progression defined as relative decline in 6-minute walking distance (6MWD) from baseline (defined as \>25% from baseline or 15-25% from baseline associated with worsening oxygen saturation, worsening Borg score, or increased oxygen requirements), respiratory-related non-elective hospitalizations, or all-cause mortality.

GroupValue95% CI
Pirfenidone+Sildenafil72.7
Pirfenidone+Placebo69.7
Time to First Occurrence of Disease Progression Secondary · Baseline up to Week 52

Disease Progression defined as relative decline in 6MWD from baseline (defined as \>25% from baseline or 15-25% from baseline associated with worsening oxygen saturation, worsening Borg score, or increased oxygen requirements), respiratory-related non-elective hospitalizations, or all-cause mortality.

GroupValue95% CI
Pirfenidone+Sildenafil26.0020.57 – 38.14
Pirfenidone+Placebo25.4313.00 – 37.71
Time to Multiple Occurrence of Disease Progression Events Secondary · Baseline up to Week 52

Disease Progression defined as relative decline in 6MWD from baseline (defined as \>25% from baseline or 15-25% from baseline associated with worsening oxygen saturation, worsening Borg score, or increased oxygen requirements), respiratory-related non-elective hospitalizations, or all-cause mortality. In case participant had more than one event as described in the endpoint definition the second, third etc event was counted as well for the calculation of the endpoint.

GroupValue95% CI
Pirfenidone+Sildenafil20.5713.14 – 26.43
Pirfenidone+Placebo13.2912.71 – 23.29
Percentage of Participants With Decline From Baseline in 6-minute Walking Distance (6MWD) of >= 15% Secondary · Baseline up to Week 52
GroupValue95% CI
Pirfenidone+Sildenafil53.4
Pirfenidone+Placebo50.6
Time to First Occurrence of Relevant ≥15% Decline From Baseline in 6-minute Walking Distance (6MWD) Secondary · Baseline up to Week 52
GroupValue95% CI
Pirfenidone+Sildenafil39.0027.86 – 52.14
Pirfenidone+Placebo38.7125.14 – 52.57
Time to Respiratory-Related Non-Elective Hospitalization From Baseline to Week 52 Secondary · Baseline up to Week 52

N.A. = non-calculable

GroupValue95% CI
Pirfenidone+Sildenafil54.2936.29 – NA
Pirfenidone+PlaceboNA42.14 – NA
Time to All-Cause Non-Elective Hospitalization Secondary · Baseline up to Week 52

N.A. = non-calculable

GroupValue95% CI
Pirfenidone+Sildenafil47.5728.00 – NA
Pirfenidone+Placebo49.8632.00 – NA
Time to Death From Any Cause Secondary · Baseline up to Week 52
GroupValue95% CI
Pirfenidone+SildenafilNA54.43 – NA
Pirfenidone+PlaceboNANA – NA
Percentage of Participants With Lung Transplantation Secondary · Baseline up to Week 52
GroupValue95% CI
Pirfenidone+Sildenafil10.2
Pirfenidone+Placebo6.7
Time to Respiratory-Related Death Secondary · Baseline up to Week 52
GroupValue95% CI
Pirfenidone+SildenafilNA54.43 – NA
Pirfenidone+PlaceboNANA – NA
Change From Baseline to Week 52 in Transthoracic Echocardiography (ECHO) Parameter: Peak Tricuspid Regurgitation Velocity Secondary · Baseline, Week 52
GroupValue95% CI
Pirfenidone+Sildenafil-0.014± 0.6326
Pirfenidone+Placebo0.103± 0.6699
Change From Baseline to Week 52 in Transthoracic Echocardiography (ECHO) Parameter: Pulmonary Artery Pressure (PAPs) Secondary · Baseline, Week 52
GroupValue95% CI
Pirfenidone+Sildenafil2.0± 15.65
Pirfenidone+Placebo3.6± 22.38

Adverse events — posted to ClinicalTrials.gov

Time frame: From baseline to primary data cut-off (up to 2 years 7 months). The safety data includes DBP and SFU up to 11-Nov-2019.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Pirfenidone+Sildenafil
Serious: 54/88 (61%)
Deaths: 28/88
Pirfenidone+Placebo
Serious: 55/89 (62%)
Deaths: 36/89

Serious adverse events (72 terms)

ReactionSystemPirfenidone+SildenafilPirfenidone+Placebo
Idiopathic pulmonary fibrosisRespiratory, thoracic and mediastinal disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
PneumoniaInfections and infestations
Respiratory failureRespiratory, thoracic and mediastinal disorders
Cardiac arrestCardiac disorders
Lower respiratory tract infectionInfections and infestations
Pulmonary fibrosisRespiratory, thoracic and mediastinal disorders
Right ventricular failureCardiac disorders
DeathGeneral disorders
Respiratory tract infectionInfections and infestations
Cardiac failureCardiac disorders
Cardio-respiratory arrestCardiac disorders
Acute respiratory failureRespiratory, thoracic and mediastinal disorders
Pulmonary embolismRespiratory, thoracic and mediastinal disorders
Pulmonary hypertensionRespiratory, thoracic and mediastinal disorders
BronchitisInfections and infestations
InfluenzaInfections and infestations
Upper respiratory tract infectionInfections and infestations
DizzinessNervous system disorders
Angina pectorisCardiac disorders
Cardiac failure acuteCardiac disorders
Cardiac failure chronicCardiac disorders
Cardiac failure congestiveCardiac disorders
Coronary artery diseaseCardiac disorders
Supraventricular tachycardiaCardiac disorders
Other adverse events (17 terms — click to expand)

ReactionSystemPirfenidone+SildenafilPirfenidone+Placebo
DyspnoeaRespiratory, thoracic and mediastinal disorders
DiarrhoeaGastrointestinal disorders
BronchitisInfections and infestations
Respiratory tract infectionInfections and infestations
Decreased appetiteMetabolism and nutrition disorders
CoughRespiratory, thoracic and mediastinal disorders
HypotensionVascular disorders
FatigueGeneral disorders
Upper respiratory tract infectionInfections and infestations
Idiopathic pulmonary fibrosisRespiratory, thoracic and mediastinal disorders
HeadacheNervous system disorders
VomitingGastrointestinal disorders
Oedema peripheralGeneral disorders
InfluenzaInfections and infestations
Weight decreasedInvestigations
DizzinessNervous system disorders
PruritusSkin and subcutaneous tissue disorders

Most-reported serious reactions: Idiopathic pulmonary fibrosis, Dyspnoea, Pneumonia, Respiratory failure, Cardiac arrest, Lower respiratory tract infection, Pulmonary fibrosis, Right ventricular failure.

Data from ClinicalTrials.gov NCT02951429 adverse events section.

Sponsor's own description

This Phase IIb, randomized, placebo-controlled, multicenter, international study will evaluate the efficacy, safety, and tolerability of sildenafil or placebo added to pirfenidone (Esbriet) treatment in participants with advanced IPF and intermediate or high probability of Group 3 pulmonary hypertension (PH) who are on a stable dose of pirfenidone with demonstrated tolerability. Participants will be randomized to receive 1 year of treatment with either oral sildenafil or matching placebo while continuing to take pirfenidone.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. The therapy of idiopathic pulmonary fibrosis: what is next?
    Somogyi V, Chaudhuri N, Torrisi SE, Kahn N, et al · · 2019 · cited 183× · PMID 31484664 · DOI 10.1183/16000617.0021-2019
  2. Antifibrotic therapy for idiopathic pulmonary fibrosis: time to treat.
    Maher TM, Strek ME. · · 2019 · cited 182× · PMID 31492155 · DOI 10.1186/s12931-019-1161-4
  3. Phosphodiesterase 5 inhibitors for pulmonary hypertension.
    Barnes H, Brown Z, Burns A, Williams T. · · 2019 · cited 97× · PMID 30701543 · DOI 10.1002/14651858.cd012621.pub2
  4. Efficacy and safety of sildenafil added to pirfenidone in patients with advanced idiopathic pulmonary fibrosis and risk of pulmonary hypertension: a double-blind, randomised, placebo-controlled, phase 2b trial.
    Behr J, Nathan SD, Wuyts WA, Mogulkoc Bishop N, et al · · 2021 · cited 95× · PMID 32822614 · DOI 10.1016/s2213-2600(20)30356-8
  5. Comorbidities in idiopathic pulmonary fibrosis: an underestimated issue.
    Caminati A, Lonati C, Cassandro R, Elia D, et al · · 2019 · cited 86× · PMID 31578211 · DOI 10.1183/16000617.0044-2019
  6. Comorbid Conditions in Idiopathic Pulmonary Fibrosis: Recognition and Management.
    Oldham JM, Collard HR. · · 2017 · cited 59× · PMID 28824912 · DOI 10.3389/fmed.2017.00123
  7. Pulmonary Hypertension Associated with Idiopathic Pulmonary Fibrosis: Current and Future Perspectives.
    Collum SD, Amione-Guerra J, Cruz-Solbes AS, DiFrancesco A, et al · · 2017 · cited 51× · PMID 28286407 · DOI 10.1155/2017/1430350
  8. Utility of the six-minute walk test in patients with idiopathic pulmonary fibrosis.
    Lancaster LH. · · 2018 · cited 40× · PMID 30559965 · DOI 10.1186/s40248-018-0158-z

Verify or expand the search:

Other trials of Pirfenidone

Trials testing the same drug.

Other recruiting trials for Idiopathic Pulmonary Fibrosis

Currently open trials in the same condition.

Other Hoffmann-La Roche trials

Trials by the same sponsor.

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Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT02951429.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing