Pulmonary Rehab in COPD: Response to Tyvaso

Tracking Information
First Submitted Date ICMJE	June 22, 2014
First Posted Date ICMJE	July 1, 2014
Last Update Posted Date	August 18, 2017
Actual Study Start Date ICMJE	August 2015
Estimated Primary Completion Date	July 2020 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: June 30, 2014)	distance walked on 6MWT [ Time Frame: 9 weeks ]; To determine the effect of inhaled treprostinil, administered prior to pulmonary rehabilitation sessions, on the six minute walk test distance (6MWT) in COPD patients after completing an 8 week course of pulmonary rehabilitation
Original Primary Outcome Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT02178566 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: June 30, 2014)	Quality of Life [ Time Frame: 9 weeks ]; To assess the effect inhaled treprostinil, administered prior to pulmonary rehabilitation in COPD patients, on secondary outcomes including quality of life (as measured by the St. George's respiratory questionnaire, Clinical COPD Questionaire), BODE index, lowest nadir of oxygen saturation on 6 minute walk test, number of exacerbations, ER visits, hospitalizations, and change in measures of strength training.
Original Secondary Outcome Measures ICMJE	Same as current
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Pulmonary Rehab in COPD: Response to Tyvaso
Official Title ICMJE	Pulmonary Rehabilitation in COPD: Response to Inhaled Treprostinil (Tyvaso)
Brief Summary	The investigators' hypothesis is that pretreating patients with COPD with inhaled treprostinil prior to pulmonary rehabilitation sessions will result in improved exercise tolerance during sessions. This in turn will lead to an increased response to pulmonary rehabilitation, resulting in improved exercise tolerance and quality of life.
Detailed Description	Study Hypothesis: Our hypothesis is that pre-treating patients with COPD with inhaled treprostinil prior to pulmonary rehabilitation sessions will result in improved exercise tolerance during sessions. This in turn will lead to an increased response to pulmonary rehabilitation, resulting in improved exercise tolerance and quality of life. Study Background: Pulmonary rehabilitation (PR) is a widely accepted intervention in patients with advanced COPD. This has consistently been shown to improve patients' quality of life and functional ability. Indeed, enrollment and completion of a course of PR is a prerequisite prior to major interventions such as lung volume reduction surgery or transplantation. A typical course of PR includes 20 sessions of supervised exercise and educational activity over an 8 week period. Sessions are usually held three times per week and last between 2-3 hours each. Most patients with COPD will have a ventilatory limitation to exercise and while many are oxygen dependent, a minority of patients will have a true hypoxic limitation to exercise. Nonetheless, when patients with COPD are ambulated on oxygen they feel better and walk further. Indeed, supplemental oxygen remains one of the few interventions that have been demonstrated to be associated with improved survival in patients with COPD. There have been a few studies and case reports utilizing inhaled pulmonary vasodilators in patients with COPD, although none to date have used treprostinil. One study of 10 patients with COPD and pulmonary hypertension found improved gas exchange and exercise tolerance following using of inhaled iloprost an alternative inhaled pulmonary vasodilator. No adverse effects were observed. [Dernaika TA, Beavin M, Kinasewitz GT. Iloprost improves gas exchange and exercise tolerance in patients with pulmonary hypertension and chronic obstructive pulmonary disease. Respiration; 2010: 79(5): 377-382.)] A case report of a patient with pulmonary hypertension and COPD found sustained improvements in exercise tolerance with regular use of inhaled iloprost. [Hegewald MJ, Elliott CG. Sustained improvement with iloprost in a COPD patient with severe pulmonary hypertension. Chest 2009; 135(2): 536-537.] While these limited trials support the concept of physiologic improvement with use of inhaled pulmonary vasodilators in COPD, our study differs from these in several important ways. This study is unique in that there has never been a prior similar study of medication pretreatment prior to PR to enhance exercise performance in any patient subgroup. Furthermore, treprostinil has not yet been evaluated for use on an as needed basis. Indication Studied: COPD/Pulmonary rehabilitation Study Objectives: Primary Objective: To determine the effect of inhaled treprostinil, administered prior to pulmonary rehabilitation sessions, on the six minute walk test distance (6MWT) in COPD patients after completing an 8 week course of pulmonary rehabilitation; Secondary Objectives: To assess the effect inhaled treprostinil, administered prior to pulmonary rehabilitation in COPD patients, on secondary outcomes including quality of life (as measured by the St. George's respiratory questionnaire, Clinical COPD Questionaire), BODE index, lowest nadir of oxygen saturation on 6 minute walk test, number of exacerbations, ER visits, hospitalizations, and change in measures of strength training. Trial Design: An adaptive, prospective, randomized, double-blind, placebo-controlled study of 34 patients with advanced COPD who have been referred for pulmonary rehabilitation. All patients will be screened at baseline with an arterial blood gas. A test dose of inhaled nitric oxide (NO) will be administered to all subjects for 2-5 minutes. An ABG will then be repeated. Patients who have a worsened A-a gradient will be screened out. Patients will be randomized to receive one dose of inhaled treprostinil or placebo prior to each of their exercise sessions. All patients will be pretreated with albuterol prior to the dose of inhaled treprostinil (or placebo). Patient Population: We plan to screen 50 patients with a goal of enrolling 34 patients. Patients referred for pulmonary rehabilitation at Inova Fairfax Hospital with moderate to severe COPD as a primary diagnosis will be screened for inclusion in the trial. Inclusion and exclusion criteria are listed below.
Study Type ICMJE	Interventional
Study Phase	Phase 2
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
Condition ICMJE	Chronic Obstructive Pulmonary Disease (COPD)
Intervention ICMJE	Drug: Inhaled Treprostinil; A dose of inhaled treprostinil or placebo will be administered to all study participants prior to each of their Pulmonary Rehab sessions. Three puffs of inhaled treprostinil dose will be administered each time to all patients .; Other Name: Tyvaso
Study Arms	Placebo Comparator: Inhaled Treprostinil Placebo A dose of placebo resembling inhaled treprostinil will be administered to all study participants in the placebo comparator arm prior to each of their Pulmonary Rehab sessions. A dose of inhaled albuterol will be administered prior to each inhaled agent. Vitals signs will be taken prior to administering the dose and no medication will be given if the systolic blood pressure in < 85 mm Hg. Three puffs of inhaled trepostinil dose will be administered each time to all patients . Intervention: Drug: Inhaled Treprostinil; Active Comparator: Inhaled Treprostinil A dose of inhaled treprostinil will be administered to all study participants prior to each of their Pulmonary Rehab sessions. A dose of inhaled albuterol will be administered prior to each inhaled agent. Vitals signs will be taken prior to administering the dose and no medication will be given if the systolic blood pressure in < 85 mm Hg. Three puffs of inhaled treprostinil dose will be administered each time to all patients . Intervention: Drug: Inhaled Treprostinil
Publications *	Dernaika TA, Beavin M, Kinasewitz GT. Iloprost improves gas exchange and exercise tolerance in patients with pulmonary hypertension and chronic obstructive pulmonary disease. Respiration. 2010;79(5):377-82. doi: 10.1159/000242498. Epub 2009 Sep 25.; Hegewald MJ, Elliott CG. Sustained improvement with iloprost in a COPD patient with severe pulmonary hypertension. Chest. 2009 Feb;135(2):536-537. doi: 10.1378/chest.08-1515.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Recruiting
Estimated Enrollment ICMJE; (submitted: June 30, 2014)	34
Original Estimated Enrollment ICMJE	Same as current
Estimated Study Completion Date	October 2020
Estimated Primary Completion Date	July 2020 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Willing to sign informed consent prior to initiation of any study mandated procedure; Male or female ≥ 40 years of age; Women of childbearing potential must use a reliable method of contraception from screening until 1 month after end of study medication; Clinical diagnosis of moderate to severe COPD, with an obstructive pattern on pulmonary function tests showing both: FEV1/FVC < 0.7 and FEV1 ≤ 60% of predicted value, on standard COPD therapy; Current or past smokers of ≥ 10 pack years; If taking oral (< 20 mg/day of prednisone equivalent) or inhaled corticosteroids, inhaled beta-agonists (short and long acting), or inhaled muscarinic antagonists (short and long acting), or statins the dose must be stable for at least 30 days prior to initial PR visit.; Ability to adequately participate in exercise testing/pulmonary rehabilitation program with supplemental oxygen use over the period of the study (in the best opinion of the investigator) Exclusion Criteria: Patients fulfilling one or more of the following criteria of documented COPD exacerbation within 1 months prior to screening: Use of antibiotics for COPD exacerbation Initiation or dose increase of steroids (inhaled, oral or intravenous) for COPD exacerbation Hospitalization for COPD exacerbation; BMI > 40 kg/m2; Unstable coronary artery disease, unstable angina, or myocardial infarction within 3 months prior to screening; History of pulmonary edema, or uncontrolled heart failure; Uncontrolled systemic hypertension with a blood pressure >180/105 mmHg at rest; Systemic hypotension with systolic blood pressure < 85 mmHg; Uncontrolled arrhythmias; History of syncope; Planned surgical intervention during the study period; Any known factor or disease that might interfere with treatment compliance, study conduct or interpretation of the results including musculo-skeletal limitations, peripheral arterial disease, drug or alcohol dependence or psychiatric disease; Severe hepatic impairment (Child-Pugh Class C); Chronic renal insufficiency, as defined by serum creatinine of > 2.5 mg/dL or estimated creatinine clearance < 30 mL/min or the requirement for dialysis; Pregnant or nursing; Currently (within 30 days prior to enrollment) taking specific pulmonary arterial hypertension therapy (e.g., bosentan, ambrisentan, tadalafil, sildenafil, epoprostenol, treprostinil, iloprost, beraprost), sildenafil and tadalafil for erectile dysfunction is permitted; Initiation of a pulmonary rehabilitation program within 3 months prior to screening or initiation or changes during the study; Participation in any other clinical trial, except observational, or receipt of an investigational medicinal product within 30 days prior to RHC visit; Known concomitant life-threatening disease with a life expectancy < 6 months; Known hypersensitivity to treprostinil or any of the excipients of the drug formulations.; Known hypersensitivity to inhaled nitric oxide
Sex/Gender	Sexes Eligible for Study: All
Ages	40 Years and older (Adult, Older Adult)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact: Christopher King, MD 703-776-3582 christopher.king@inova.org Contact: Edwinia Battle, RN, BSN 703-776-3067 edwinia.battle@inova.org
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT02178566
Other Study ID Numbers ICMJE	Inova-TY-PR-001
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Inova Health Care Services
Study Sponsor ICMJE	Inova Health Care Services
Collaborators ICMJE	Not Provided
Investigators ICMJE	Principal Investigator: Steven Nathan, MD Inova Fairfax Medical Campus Principal Investigator: Christopher King, MD Inova Fairfax Medical Campus
PRS Account	Inova Health Care Services
Verification Date	August 2017
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP