High Oxygen Delivery to Preserve Exercise Capacity in Idiopathic Pulmonary Fibrosis Patients Treated With Nintedanib

Study Overview
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Brief Summary
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The purpose is to determine if patients with idiopathic pulmonary fibrosis (IPF) taking nintedanib will have improved exercise endurance, breathlessness and quality of life if breathing 60% oxygen compared to standard of care during an 8 week exercise training program.

Detailed Description
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Pulmonary rehabilitation is a structured evidence-based exercise and education intervention that is recommended for most patients with IPF. Pulmonary rehabilitation improves functional capacity (6-minute walk distance [6MWD]), breathlessness and quality of life in patients, however these benefits are often modest and only temporary. Nintedanib is an antifibrotic medication that has been shown to slow the decline of lung function. Use of antifibrotic medications in the pulmonary rehabilitation setting may therefore allow prolonged benefit of exercise training by preventing IPF progression and the resulting worsening symptoms and functional decline. Unpublished data suggest that breathing 60% oxygen in a pulmonary rehabilitation setting could enable patients to train at higher exercise intensities and thus derive greater physiological adaptations and clinical benefits compared with traditional pulmonary rehabilitation. This is a randomized, blinded study with two arms (standard of care or 60% oxygen). The decision to start or stop treatment with nintedanib will be made by the participants treating physician based on clinical findings. If the treating physician decides to discontinue nintedanib, the participant will be allowed to continue in the study. The exercise training program is 8 weeks long, with visits 3 times a week. In addition to the exercise training there are 13 visits occurring before, during and after the 8 week exercise training program. At study visits, participants will be required to conduct a 6 minute walk test and complete a quality of life questionnaire. Select study visits will also require lung function tests and exercise tests to be conducted.

Official Title
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High Oxygen Delivery to Preserve Exercise Capacity in IPF Patients Treated With Nintedanib: The HOPE-IPF Study

Conditions
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Idiopathic Pulmonary Fibrosis

Intervention / Treatment
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* Other: 60% Oxygen
* Other: Standard of Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 19 years or older Idiopathic Pulmonary Fibrosis (IPF) diagnosis according to American Thoracic Society and/or European Respiratory Society consensus criteria Appropriate candidate for pulmonary rehabilitation prescribed nintedanib by their treating physician or currently on nintedanib 6 minute walk distance 50m or more Oxygen saturation 92% or more by pulse oximetry at rest while breathing room air Clinically stable for the preceding 6 weeks Exclusion Criteria: Contraindication to treatment with nintedanib (based on Canadian labeling) Contraindication to exercise testing (e.g. significant cardiovascular, musculoskeletal, neurological disease) Other significant extra-pulmonary disease that, based on clinical assessment, could impair exercise capacity and/or oxygenation Forced vital capacity (FVC) less than 50% or Diffusion capacity for carbon monoxide (DLCO) less than 25% Concurrent or recent participation (less than 6 months) in a pulmonary rehabilitation program Use of prednisone greater than 10 mg/day for more than 2 weeks within 3 months of the first study visit Use of pirfenidone within 4 weeks of screening Significant emphysema (less than 10% volume on high resolution computed tomography (HRCT) or forced expiratory volume at one second (FEV1)/FVC less than 0.70)

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 60% Oxgyen<br>While participants are exercising, they will be breathing 60% oxygen through a mask. | Other: 60% Oxygen<br>* While participants are exercising, they will be inhaling 60% oxygen through a mask<br>|
| Placebo Comparator: Standard of Care<br>While participants are exercising, they will be breathing air through a mask that will be titrated to keep oxygen saturation at least 88%, allowing a maximum inhaled oxygen percentage of 40%. | Other: Standard of Care<br>* While participants are exercising, they will be breathing air through a mask that will be titrated to keep oxygen saturation at least 88%, allowing a maximum inhaled oxygen percentage of 40%.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in exercise duration during the constant load exercise test at 8 weeks | An constant load exercise test on a stationary bike will be performed. Patients will be told to exercise for as long as possible and endurance time will be defined as the duration of the constant load exercise test. | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in 6 Minute Walk Distance (6MWD) at 8 weeks | Patients will be asked to walk, at their own pace, as far as they can in 6 minutes. | 8 weeks | 
| Change in the amount a patient is troubled by their breathlessness at 8 weeks | Measured using the modified Medical Research Council dyspnea scale (mMRC) | 8 weeks | 
| Change in the amount a patient is troubled by their breathlessness during the 6 Minute Walk Distance test at 8 weeks | Measured using the 10-point Borg scale during 6MWD | 8 weeks | 
| Change in the amount a patient is troubled by their breathlessness during the cycle exercise test at 8 weeks | Measured using the 10-point Borg scale during cycle exercise tests | 8 weeks | 
| Change in how much shortness of breath the patient experiences while doing normal activities at 8 weeks | Measured using the University of California San Diego Shortness of Breath Questionnaire (UCSD SOBQ). | 8 weeks | 
| Change in the amount of physical work a patient can do before becoming breathless at 8 weeks | Measured using the oxygen cost diagram (OCD). | 8 weeks | 
| Patient reported change in amount of physical activity at 8 weeks | Physical activity will be measured using the long form of the international physical activity questionnaire (IPAQ-LF). | 8 weeks | 
| Change in amount of physical activity at 8 weeks | Physical activity will be measured objectively using the Fit Bit activity monitor. | 8 weeks | 
| Change in Quality of Life at 8 weeks | Disease-specific quality of life will be measured using the St. George's Respiratory Questionnaire (SGRQ). | 8 weeks |