Clinical trial NCT01979952: Nintedanib Twice Daily vs Placebo in Patients Diagnosed With Idiopathic Pulmonary Fibrosis (IPF)
Official title: A Six Month Double Blind Randomized Placebo Controlled Trial Followed by Each Arm Being Converted to Oral Nintedanib 150 mg Twice Daily Comparing the Effect on High Resolution Computerized Tomography Quantitative Lung Fibrosis Score, Lung Function, Six Minute Walk Test Distance and St. George's Respiratory Questionnaire After Six Months of Treatment in Patients With Idiopathic Pulmonary Fibrosis With Continued Evaluations Over a Period of up to Eighteen Months
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Idiopathic Pulmonary Fibrosis
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2013-11-08
Enrollment: 113
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is an 6 month multi-centre, prospective, randomized, placebo controlled, double blind clinical trial followed by conversion of each arm to active nintedanib for an additional 6 months comparing the effect of nintedanib 150mg bis in die (BID twice daily) on the progression of IPF measured by using High Resolution Computerized Tomography(HRCT), lung function, functional component (6MWT), biomarkers, and PRO component (PROs) with continued treatment and assessments for up to 18 months.


Eligibility criteria: Inclusion criteria:

1. Written Informed Consent consistent with International Conference on Harmonisation Good Clinical Practice (ICH-GCP) and local laws signed prior to entry into the study
2. Patient aged \>= 40 years at Visit 1.
3. IPF diagnosed, according to the 2011 American Thoracic Society (ATS) / European Respiratory Society (ERS) / Japanese Respiratory Society(JRS)/ Latin American Thoracic Association (ALAT)/ Latin American Thoracic Association/ Idiopathic Pulmonary Fibrosis (IPF) guidelines for diagnosis and management, within 5 years and reaffirmed applying 2011 Guidelines (P11-07084) if diagnosed \>2 years and up to 5 year from Visit 1,. Diagnosis must be confirmed by chest High Resolution Computerized Tomography (HRCT) taken within 24 months of Visit 1. All HRCT results reported to be possible or inconsistent usual interstitial pneumonia (UIP) must have confirmatory pathology.
4. Carbon monoxide Diffusing capacity or Transfer factor of the lung for carbon monoxide (DLCO) (corrected for Hb): 30%-79% predicted of normal
5. Forced Vital Capacity (FVC) \>= 50% predicted of normal at Visit 1 and Visit 2

Exclusion criteria:

1. AST, ALT \> 1.5 fold ULN
2. Bilirubin \> 1.5 fold ULN
3. Bleeding risk:

   1. Patients who require fibrinolysis, full-dose therapeutic anticoagulation (e.g. vitamin K antagonists, dabigatran, heparin, hirudin), or high dose antiplatelet therapy. Exceptions: prophylactic low dose heparin or heparin flush as needed for maintenance of an indwelling intravenous device (e.g. enoxaparin 4000 IU s.c. per day) and prophylactic use of antiplatelet therapy (e.g. acetyl salicylic acid up to 325 mg/d, or clopidogrel at 75 mg/d, or equivalent doses of other antiplatelet therapy)
   2. History of hemorrhagic Central Nervous System (CNS) event within 12 months
   3. Any of the following within 3 months:

      * Haemoptysis or haematuria.
      * Active gastro-intestinal bleeding or ulcers.
      * Major injury or surgery.
   4. Coagulation parameters: International normalised ratio (INR) \> 2, prothrombin time (PT) and partial thromboplastin time (PTT) \> 150% of institutional ULN.
4. Planned major surgery within the next 3 months, including lung transplantation, major abdominal or major intestinal surgery.
5. Thrombotic risk

   1. Known inherited predisposition to thrombosis.
   2. History of thrombotic event (including stroke and transient ischemic attacks) within 12 months
6. Current or planned usage of any investigational drug during the course of this trial
7. Previous treatment with nintedanib within a clinical trial in the previous 3 months and discontinuation of nintedanib study treatment due to an adverse event
8. Known hypersensitivity to the trial drug or its component
9. A disease or condition which in the opinion of investigator may put the patient at risk because of participation in this trial or limit the patient's ability to participate in this trial. Patients will be excluded if they require greater than 12L/min oxygen, are not ambulatory or require use of a walker or cane during the 6 Minute Titration Walk Test. Patients who cannot complete the 6 Minute Titration Walk Test are excluded from participation.
10. Alcohol or drug abuse which in the opinion of the investigator would interfere with trial participation.
11. Pregnant women or women who are breast feeding or of child bearing potential not using two effective methods of birth control (one barrier and one highly effective non-barrier) for at least 1 month prior to trial and/or not committing to using it until 3 months after end of treatment.

Primary outcomes:
measure: Relative Change From Baseline in High Resolution Computerized Tomography (HRCT) Quantitative Lung Fibrosis (QLF) Score at 6 Months
timeFrame: Baseline and 6 Months
Secondary outcomes:
measure: Effect of Six Month Delayed Treatment Onset: Relative Change From Baseline in HRCT QLF Score at 12 Months
timeFrame: Baseline and 12 Months
measure: Absolute Change in Forced Vital Capacity (FVC) From Baseline at 6 Months
timeFrame: Baseline and 6 Months
measure: Relative Change in FVC From Baseline at 6 Months
timeFrame: Baseline and 6 Months
measure: Categorical Change in FVC From Baseline at 6 Months
timeFrame: Baseline and 6 Months
measure: St. George's Respiratory Questionnaire (SGRQ) Total Score Change From Baseline at 6 Months
timeFrame: Baseline and 6 Months
measure: 6MWT Total Distance Walked Change From Baseline at 6 Months
timeFrame: Baseline and 6 Months
measure: University of California San Diego Shortness of Breath Questionnaire (UCSD-SOBQ) Change From Baseline at 6 Months
timeFrame: Baseline and 6 Months
measure: All-cause Mortality at 6 Months
timeFrame: 6 Months
measure: Respiratory Hospitalizations at 6 Months
timeFrame: 6 Months
measure: Respiratory Mortality at 6 Months
timeFrame: 6 Months
measure: Acute Idiopathic Pulmonary Fibrosis (IPF) Exacerbations at 6 Months
timeFrame: 6 Months
Other outcomes:
Locations:
city: Danbury
country: United States
facility: Western CT Medical Group, P.C.
state: Connecticut
city: Sarasota
country: United States
facility: Clinical Research Center Sarasota Memorial Hosptial
state: Florida
city: Skokie
country: United States
facility: Chest Medicine Clinical Services
state: Illinois
city: Lexington
country: United States
facility: Baptist Health Lexington
state: Kentucky
city: Minneapolis
country: United States
facility: Minnesota Lung Research
state: Minnesota
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Mineola
country: United States
facility: Winthrop University Hospital
state: New York
city: Toledo
country: United States
facility: ID Clinical Research, LTD
state: Ohio
city: Portland
country: United States
facility: The Oregon Clinic
state: Oregon
city: Charleston
country: United States
facility: Lowcountry Lung and Crit Care
state: South Carolina
city: Dallas
country: United States
facility: Annette C & Harold C Simmons Transplant Institute
state: Texas
city: Edmonton
country: Canada
facility: University of Alberta Hospital (University of Alberta)
state: Alberta
city: Vancouver
country: Canada
facility: Vancouver General Hospital
state: British Columbia
city: Vancouver
country: Canada
facility: St. Paul's Hospital
state: British Columbia
city: Winnipeg
country: Canada
facility: Concordia Hospital
state: Manitoba
city: Halifax
country: Canada
facility: QEII Health Sciences Centre (Dalhousie University)
state: Nova Scotia
city: Hamilton
country: Canada
facility: St. Joseph's Healthcare Hamilton
state: Ontario
city: Sherbrooke
country: Canada
facility: CHUS Fleurimont
state: Quebec
city: Adana
country: Turkey
facility: Cukurova Universitesi Tip Fakultesi Gog. Hast. Anabilim Dali
city: Ankara
country: Turkey
facility: Ankara Universitesi Tip Fakultesi
city: Istanbul
country: Turkey
facility: Istanbul Universitesi Cerrahpasa Tip Fakultesi
city: Istanbul
country: Turkey
facility: Yedikule Gog. Hst. EAH
city: Istanbul
country: Turkey
facility: Sureyyapasa Gogus Hast. ve Gogus Cer. Egit. ve Aras. Has.
city: Izmir
country: Turkey
facility: Ege Universitesi T.F.
city: Izmir
country: Turkey
facility: Dr.Suat Seren EAH
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: Glaspole I, Bonella F, Bargagli E, Glassberg MK, Caro F, Stansen W, Quaresma M, Orsatti L, Bendstrup E. Efficacy and safety of nintedanib in patients with idiopathic pulmonary fibrosis who are elderly or have comorbidities. Respir Res. 2021 Apr 26;22(1):125. doi: 10.1186/s12931-021-01695-y.