Efficacy and Safety of Nintedanib Co-administered With Sildenafil in Idiopathic Pulmonary Fibrosis Patients With Advanced Lung Function Impairment
INSTAGE: A 24-week, Double-blind, Randomized, Parallel-group Study Evaluating the Efficacy and Safety of Oral Nintedanib Co-administered With Oral Sildenafil, Compared to Treatment With Nintedanib Alone, in Patients With Idiopathic Pulmonary Fibrosis (IPF) and Advanced Lung Function Impairment
2 other identifiers
interventional
274
13 countries
85
Brief Summary
To assess efficacy and safety of concomitant treatment with nintedanib and sildenafil in Idiopathic Pulmonary Fibrosis (IPF) patients with advanced lung function impairment.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Jun 2016
85 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 14, 2016
CompletedFirst Posted
Study publicly available on registry
June 16, 2016
CompletedStudy Start
First participant enrolled
June 30, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 19, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
April 13, 2018
CompletedResults Posted
Study results publicly available
January 11, 2019
CompletedJanuary 11, 2019
December 1, 2018
1.5 years
June 14, 2016
December 17, 2018
December 17, 2018
Conditions
Outcome Measures
Primary Outcomes (1)
Change From Baseline in St George's Respiratory Questionnaire (SGRQ) Total Score at Week 12
The SGRQ is a 50-item questionnaire developed to measure health status (quality of life). Scores are calculated for three domains: Symptoms, Activity and Impacts (Psycho-social) as well as a total score. A minimum change in score of 4 units was established as clinically relevant after patient and clinician testing. Scores range from 0 to 100, with higher scores indicating more limitations. The mean and standard error presented are actually adjusted mean for change from baseline and its standard error.
Baseline and week 12
Secondary Outcomes (4)
Change From Baseline in Dyspnoea Using the University of California San Diego Shortness of Breath Questionnaire (UCSD SOBQ) at Week 12
Baseline and week 12
Change From Baseline in SGRQ Total Score at Week 24
Baseline and week 24
Change From Baseline in Dyspnoea Using UCSD SOBQ at Week 24
Baseline and week 24
Percentage of Patients With On-treatment Serious Adverse Events (SAE) From Baseline to Week 24
Baseline and week 24
Study Arms (2)
Nintedanib + placebo matching sildenafil
EXPERIMENTALNintedanib + Sildenafil
ACTIVE COMPARATORInterventions
Eligibility Criteria
You may qualify if:
- Written informed consent consistent with International Conference on Harmonization-Good Clinical Practice and local laws, signed prior to any study procedures being performed (including any required washout);
- Male or female patients aged \>= 40 years at visit 1;
- A clinical diagnosis of IPF within the last 6 years before visit 1, based upon the American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/Latin American thoracic Association 2011 guideline \[P11-07084\];
- Combination of high-resolution computed tomography (HRCT) pattern, and if available, surgical lung biopsy pattern consistent with a diagnosis of IPF as assessed by the investigator based on a HRCT scan performed within 18 months of visit 1;
- Carbon Monoxide Diffusion Capacity (corrected for Hb) less or equal to 35% predicted of normal at visit 1.
You may not qualify if:
- Previous enrolment in this trial;
- Alanine Transaminase, Aspartate Transaminase \> 1.5 fold upper limit of normal (ULN) at visit 1;
- Total bilirubin \> 1.5 fold ULN at visit 1;
- Relevant airways obstruction (i.e. pre-bronchodilator Forced Expiratory Volume in 1 second/Forced Vital Capacity \<0.7 at visit 1)
- History of myocardial infarction within 6 months of visit 1 or unstable angina within 1 month of visit 1
- Bleeding Risk:
- Known genetic predisposition to bleeding;
- Patients who require fibrinolysis, full-dose therapeutic anticoagulation (e.g. vitamin K antagonists, direct thrombin inhibitors, heparin, hirudin, etc.) or high dose antiplatelet therapy;
- History of haemorrhagic central nervous system (CNS) event within 12 months prior to visit 1;
- History of haemoptysis or haematuria, active gastro-intestinal bleeding or ulcers and/or major injury or surgery within 3 months prior to visit 1;
- International normalised ratio (INR) \> 2 at visit 1;
- Prothrombin time (PT) and activated partial thromboplastin time (aPTT) \> 150% of institutional ULN at visit 1;
- Planned major surgery during the trial participation, including lung transplantation, major abdominal or major intestinal surgery;
- History of thrombotic event (including stroke and transient ischemic attack) within 12 months of visit 1;
- Creatinine clearance \< 30 mL/min calculated by Cockcroft-Gault formula at visit 1;
- +20 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (85)
University of Alabama at Birmingham
Birmingham, Alabama, 35294, United States
Pulmonary Assoc of Stamford
Stamford, Connecticut, 06902-3633, United States
University of Florida College of Medicine
Jacksonville, Florida, 32209, United States
University of Chicago
Chicago, Illinois, 60637, United States
University of Kansas Medical Center
Kansas City, Kansas, 66160, United States
Michigan Clinical Research Unit
Ann Arbor, Michigan, 48109, United States
Minnesota Lung Center
Minneapolis, Minnesota, 55407, United States
The Lung Research Center, LLC
Chesterfield, Missouri, 63017, United States
NewYork-Presbyterian/Weill Cornell Medical Center
New York, New York, 10065, United States
Duke University Medical Center
Durham, North Carolina, 27710, United States
Clinical Research Solutions
Dayton, Ohio, 45409, United States
Mercy Respiratory Specialist
Toledo, Ohio, 43608, United States
The Oregon Clinic
Portland, Oregon, 97220, United States
Lowcountry Lung and Crit Care
Charleston, South Carolina, 29406, United States
Medical University of South Carolina
Charleston, South Carolina, 29425, United States
University of Texas Southwestern Medical Center
Dallas, Texas, 75235, United States
Pulmonary Associates of Richmond, Inc.
Richmond, Virginia, 23225, United States
Royal Prince Alfred Hospital
Camperdown, Sydney, New South Wales, 2050, Australia
Royal Adelaide Hospital
Adelaide, South Australia, 5000, Australia
The Alfred Hospital
Melbourne, Victoria, 3004, Australia
Ziekenhuis Netwerk Antwerpen (ZNA) - Campus Middelheim
Antwerp, 2020, Belgium
ULB Hopital Erasme
Brussels, 1070, Belgium
UZ Leuven
Leuven, 3000, Belgium
University of Alberta Hospital (University of Alberta)
Edmonton, Alberta, T6G 2G3, Canada
St. Paul's Hospital
Vancouver, British Columbia, V6Z 1Y6, Canada
QEII Health Sciences Centre (Dalhousie University)
Halifax, Nova Scotia, B3H 3A7, Canada
St. Joseph's Healthcare Hamilton
Hamilton, Ontario, L8N 4A6, Canada
Toronto General Hospital
Toronto, Ontario, M5G 2N2, Canada
HOP Louis Pradel
Bron, 69677, France
HOP Calmette
Lille, 59037, France
HOP Nord
Marseille, 13015, France
HOP Arnaud de Villeneuve
Montpellier, 34950, France
HOP Pasteur
Nice, 06001, France
HOP Européen G. Pompidou
Paris, 75015, France
HOP Bichat
Paris, 75018, France
HOP Pontchaillou
Rennes, 35033, France
Fachkrankenhaus Coswig GmbH
Coswig, 01640, Germany
Ruhrlandklinik, Westdeutsches Lungenzentrum am Universitätsklinikum Essen gGmbH
Essen, 45239, Germany
Universitätsklinikum Freiburg
Freiburg im Breisgau, 79106, Germany
Universitätsklinikum Gießen und Marburg GmbH
Giessen, 35392, Germany
Universitätsmedizin Greifswald
Greifswald, 17475, Germany
Medizinische Hochschule Hannover
Hanover, 30625, Germany
Lungenfachklinik Immenhausen
Immenhausen, 34376, Germany
Wissenschaftliches Institut Bethanien
Solingen, 42699, Germany
Sanjivani Superspeciality Hospital Pvt. Ltd.
Ahmedabad, 380015, India
Care Institute Of Medical Sciences
Ahmedabad, 380060, India
Sri Bala Medical Centre & Hospitals
Coimbatore, 641045, India
Fortis Hospital
Kolkata, India
Jehangir Clinical Development Centre Pvt. Ltd.
Pune, 411 001, India
Osp. Clin. SS. Anunziata
Chieti Scalo, 56100, Italy
Ospedale Colonnello D Avanzo
Foggia, 71100, Italy
Ospedale "G.B. Morgagni - L. Pierantoni" ausl forli
Forlì, 47121, Italy
Osp. S. Giuseppe Fatebenefratelli
Milan, 20123, Italy
Università di Modena e Reggio Emilia
Modena, 41124, Italy
Azienda Ospedaliera Universitaria di Padova
Padua, 35128, Italy
Az. Ospedaliera Universitaria Polic.Tor Vergata
Roma, 00133, Italy
Policlinico Gemelli
Roma, 00168, Italy
A.O.U. Senese Policlinico Santa Maria alle Scotte
Siena, 53100, Italy
Ospedale Riuniti di Ancona
Torrette Di Ancona (Ancona), 60126, Italy
Tosei General Hospital
Aichi, Seto, 489-8642, Japan
Kurume University Hospital
Fukuoka, Kurume, 830-0011, Japan
Ogaki Municipal Hospital
Gifu, Ogaki, 503-8502, Japan
National Hospital Organization Himeji Medical Center
Hyogo, Himeji, 670-8520, Japan
Ibarakihigashi National Hospial
Ibaraki, Naka-gun, 319-1113, Japan
Kanagawa Cardiovascular and Respiratory Center
Kanagawa, Yokohama, 236-0051, Japan
National Hospital Organization Kinki-Chuo Chest Medical Center
Osaka, Sakai, 591-8555, Japan
Nippon Medical School Hospital
Tokyo, Bunkyo-ku, 113-8603, Japan
Toho University Omori Medical Center
Tokyo, Ota-ku, 143-8541, Japan
Nuevo Hospital Civil de Guadalajara DR. JUAN I. MENCHACA
Guadalajara, 44340, Mexico
Centro Respiratorio de Mexico
México, 14050, Mexico
Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas
México, 14080, Mexico
Centro de Prevención y Rehabilitación de Enfermedades Pulmon
Monterrey, 64460, Mexico
Seoul National University Hospital
Seoul, 110-744, South Korea
Asan Medical Center
Seoul, 138-736, South Korea
Hospital Vall d'Hebron
Barcelona, 08035, Spain
Hospital Universitari de Girona Doctor Josep Trueta
Girona, 17007, Spain
Hospital Clínico San Carlos
Madrid, 28040, Spain
Hospital Quirónsalud Madrid
Pozuelo de Alarcón, 28223, Spain
Hospital General Universitario de Valencia
Valencia, 46014, Spain
Southmead Hospital
Bristol, BS10 5NB, United Kingdom
Papworth Hospital
Cambridge, CB23 3RE, United Kingdom
Ninewells Hospital & Medical School
Dundee, Scotland, DD1 9SY, United Kingdom
Queen Elizabeth University Hospital
Glasgow, G51 4TF, United Kingdom
Northern General Hospital
Sheffield, S5 7AU, United Kingdom
South Tyneside District Hospital
Tyne and Wear, NE34 0PL, United Kingdom
Related Publications (3)
Richeldi L, Kolb M, Jouneau S, Wuyts WA, Schinzel B, Stowasser S, Quaresma M, Raghu G. Efficacy and safety of nintedanib in patients with advanced idiopathic pulmonary fibrosis. BMC Pulm Med. 2020 Jan 8;20(1):3. doi: 10.1186/s12890-019-1030-4.
PMID: 31914963DERIVEDBehr J, Kolb M, Song JW, Luppi F, Schinzel B, Stowasser S, Quaresma M, Martinez FJ. Nintedanib and Sildenafil in Patients with Idiopathic Pulmonary Fibrosis and Right Heart Dysfunction. A Prespecified Subgroup Analysis of a Double-Blind Randomized Clinical Trial (INSTAGE). Am J Respir Crit Care Med. 2019 Dec 15;200(12):1505-1512. doi: 10.1164/rccm.201903-0488OC.
PMID: 31365829DERIVEDKolb M, Raghu G, Wells AU, Behr J, Richeldi L, Schinzel B, Quaresma M, Stowasser S, Martinez FJ; INSTAGE Investigators. Nintedanib plus Sildenafil in Patients with Idiopathic Pulmonary Fibrosis. N Engl J Med. 2018 Nov 1;379(18):1722-1731. doi: 10.1056/NEJMoa1811737. Epub 2018 Sep 15.
PMID: 30220235DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Boehringer Ingelheim, Call Centre
- Organization
- Boehringer Ingelheim
Study Officials
- STUDY CHAIR
Boehringer Ingelheim
Boehringer Ingelheim
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
- Expanded Access
- Yes
Study Record Dates
First Submitted
June 14, 2016
First Posted
June 16, 2016
Study Start
June 30, 2016
Primary Completion
December 19, 2017
Study Completion
April 13, 2018
Last Updated
January 11, 2019
Results First Posted
January 11, 2019
Record last verified: 2018-12