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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT02802345
Registration number
NCT02802345
Ethics application status
Date submitted
14/06/2016
Date registered
16/06/2016
Date last updated
11/01/2019
Titles & IDs
Public title
Efficacy and Safety of Nintedanib Co-administered With Sildenafil in Idiopathic Pulmonary Fibrosis Patients With Advanced Lung Function Impairment
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Scientific title
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
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Secondary ID [1]
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2015-002619-14
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Secondary ID [2]
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1199.36
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Idiopathic Pulmonary Fibrosis
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Condition category
Condition code
Respiratory
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Other respiratory disorders / diseases
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Inflammatory and Immune System
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Connective tissue diseases
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Inflammatory and Immune System
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Other inflammatory or immune system disorders
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Intervention/exposure
Study type
Interventional(has expanded access)
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Description of intervention(s) / exposure
Treatment: Drugs - Nintedanib
Treatment: Drugs - Placebo
Treatment: Drugs - Sildenafil
Experimental: Nintedanib + placebo matching sildenafil -
Active Comparator: Nintedanib + Sildenafil -
Treatment: Drugs: Nintedanib
Treatment: Drugs: Placebo
Treatment: Drugs: Sildenafil
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Change From Baseline in St George's Respiratory Questionnaire (SGRQ) Total Score at Week 12
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Assessment method [1]
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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.
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Timepoint [1]
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Baseline and week 12
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Secondary outcome [1]
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Change From Baseline in Dyspnoea Using the University of California San Diego Shortness of Breath Questionnaire (UCSD SOBQ) at Week 12
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Assessment method [1]
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The UCSD SOBQ is a 24-item questionnaire developed to measure breathlessness on a scale between zero and five where 0 is not at all breathless and 5 is maximally breathless or too breathless to do the activity. The mean and standard error presented for descriptive statistics are actually adjusted mean for change from baseline and its standard error.
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Timepoint [1]
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Baseline and week 12
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Secondary outcome [2]
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Change From Baseline in SGRQ Total Score at Week 24
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Assessment method [2]
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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. The mean and standard error presented for descriptive statistics are actually adjusted mean for change from baseline and its standard error.
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Timepoint [2]
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Baseline and week 24
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Secondary outcome [3]
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Change From Baseline in Dyspnoea Using UCSD SOBQ at Week 24
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Assessment method [3]
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The UCSD SOBQ is a 24-item questionnaire developed to to measure breathlessness on a scale between zero and five where 0 is not at all breathless and 5 is maximally breathless or too breathless to do the activity. The mean and standard error presented for descriptive statistics are actually adjusted mean for change from baseline and its standard error.
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Timepoint [3]
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Baseline and week 24
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Secondary outcome [4]
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Percentage of Patients With On-treatment Serious Adverse Events (SAE) From Baseline to Week 24
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Assessment method [4]
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Percentage of patients with on-treatment serious adverse events (SAE) from baseline to Week 24 is presented.
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Timepoint [4]
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Baseline and week 24
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Eligibility
Key inclusion criteria
Inclusion criteria:
- 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.
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Minimum age
40
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
Exclusion criteria:
- 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;
- Presence of aortic stenosis (AS) per investigator judgement at visit 1;
- Severe chronic heart failure: defined by left ventricular ejection fraction (EF) < 25%
per investigator judgement at visit 1;
- Presence of idiopathic hypertrophic subaortic stenosis (IHSS) per investigator
judgement at visit 1;
- Second-degree or third-degree atrioventricular (AV) block on electrocardiogram (ECG)
per investigator judgement at visit 1;
- Hypotension (systolic blood pressure [SBP] < 100 mm Hg or diastolic blood pressure
[DBP] < 50 mm Hg) (symptomatic orthostatic hypotension) at visit 1;
- Uncontrolled systemic hypertension (SBP > 180 mmHg; or DBP > 100 mmHg) at visit 1;
- Known penile deformities or conditions (e.g., sickle cell anemia, multiple myeloma,
leukemia) that may predispose to priapism;
- Retinitis pigmentosa;
- History of vision loss;
- History of nonarteritic ischemic optic neuropathy;
- Veno-occlusive disease;
- History of acute IPF exacerbation or respiratory infection within 8 weeks of visit 2.
- Treatment with nitrates, n-acetylcysteine, pirfenidone, azathioprine,
cyclophosphamide, cyclosporine, prednisone >15 mg daily or >30 mg every 2 days OR
equivalent dose of other oral corticosteroids as well as any investigational drug
within 4 weeks of visit 2;
- Treatment with prostaglandins (e.g., epoprostenol, treprostinil), endothelin-1
antagonists (e.g., bosentan, sitaxsentan, ambrisentan), phosphodiesterase inhibitors
(e.g., sildenafil, tadalafil, vardenafil) or a stimulator of guanylatcyclase
(e.g.,riociguat) within 4 weeks of visit 2;
- Treatment with potent cytochrome CYP3A4 inhibitors such as ketoconazole, itraconazole
and ritonavir within 4 weeks of visit 2;
- Supplementation with L-arginine and concurrent use of grapefruit juice or St John's
wort within 4 weeks of visit 2;
- Treatment with the reduced dose of nintedanib (100 mg bid) within 4 weeks of visit 2;
27. Permanent discontinuation of nintedanib in the past due to adverse events
considered drug-related;
- Known hypersensitivity or intolerance to nintedanib, sildenafil, galactose, peanut or
soya or any other components of the study medication;
- A disease or condition which in the opinion of the investigator may interfere with
testing procedures or put the patient at risk when participating in this trial;
- Alcohol or drug abuse which in the opinion of the treating physician would interfere
with treatment;
- Further exclusion criteria apply.
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Blinded (masking used)
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Who is / are masked / blinded?
The people receiving the treatment/s
The people analysing the results/data
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 3
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
30/06/2016
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
13/04/2018
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Sample size
Target
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Accrual to date
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Final
274
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Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
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Recruitment hospital [1]
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Royal Prince Alfred Hospital - Camperdown, Sydney
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Royal Adelaide Hospital - Adelaide
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The Alfred Hospital - Melbourne
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2050 - Camperdown, Sydney
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5000 - Adelaide
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Recruitment postcode(s) [3]
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3004 - Melbourne
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Recruitment outside Australia
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
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Name
Boehringer Ingelheim
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Address
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Ethics approval
Ethics application status
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Summary
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.
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Trial website
https://clinicaltrials.gov/ct2/show/NCT02802345
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
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Boehringer Ingelheim
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Boehringer Ingelheim
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT02802345
Download to PDF