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Evaluation and Treatment of Pulmonary Vascular Disease in Moderate to Severe CF

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ClinicalTrials.gov Identifier: NCT02626182
Recruitment Status : Completed
First Posted : December 10, 2015
Results First Posted : July 15, 2019
Last Update Posted : July 24, 2019
Sponsor:
Information provided by (Responsible Party):
Jennifer Taylor-Cousar, National Jewish Health

Brief Summary:
This study evaluates the ability of the drug sildenafil to improved exercise capacity, cardiac performance during exercise, and quality of life in patients with moderate to severe CF lung disease. 3/4 of the subjects will receive sildenafil and 1/4 will receive placebo.

Condition or disease Intervention/treatment Phase
Cystic Fibrosis Drug: sildenafil Drug: placebo Phase 1 Phase 2

Detailed Description:
Over time, patients with Cystic Fibrosis (CF) develop disabling lung disease that progresses to chronic respiratory failure, exercise intolerance with marked limitation of physical activity, and premature death. Despite substantial improvements in care, patients with CF often develop pulmonary vascular disease (PVD) that leads to pulmonary hypertension. Previous studies have clearly linked severe pulmonary hypertension and right heart failure with high mortality in CF. Early clinical manifestations of PVD prior to the development of cor pulmonale include shortness of breath and dyspnea with exertion, but the extent to which PVD contributes to the decline in exercise tolerance and quality of life in patients with CF is not known. Early evidence of PVD could be recognized in CF patients through standardized exercise testing and echocardiographic evaluation. Identifying those CF patients with PVD prior to the onset of right ventricular dysfunction may allow pharmacologic intervention to attenuate the progression of cardiovascular disease and improve quality of life. Clinical trials have demonstrated that treatment with the phosphodiesterase type 5 inhibitor, sildenafil, can decrease pulmonary vascular resistance and improve exercise tolerance in non-CF patients with pulmonary hypertension. Because experimental and clinical studies have implicated impaired NO-cGMP signaling in the pathophysiology of lung disease in CF, sildenafil may provide a novel pharmacological approach for treating PVD in patients with CF lung disease.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 14 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Evaluation and Treatment of Pulmonary Vascular Disease in Moderate to Severe Cystic Fibrosis Lung Disease
Study Start Date : December 2015
Actual Primary Completion Date : January 18, 2018
Actual Study Completion Date : January 29, 2018


Arm Intervention/treatment
Experimental: Sildenafil
Subjects will be randomized in a 3:1 (sildenafil:placebo) fashion. Subjects randomized to the treatment arm will receive sildenafil 20 mg p.o. t.i.d for 1 week followed by 40 mg p.o. t.i.d. for 11 weeks.
Drug: sildenafil
active sildenafil
Other Name: Revatio, Viagra

Placebo Comparator: Placebo
Subjects randomized to the placebo arm will receive placebo p.o. t.i.d for 1 week followed by 2 placebo tablets p.o. t.i.d. for 11 weeks.
Drug: placebo
sugar pill that looks like sildenafil tablets




Primary Outcome Measures :
  1. 6 Minute Walk Distance [ Time Frame: Weeks 1, 13 ]
    Change in distance walked between week 1 and week 13 were compared. The difference between the two time points is reported.

  2. Cardiopulmonary Exercise Test Work Rate [ Time Frame: Weeks 1 and 13 ]
    Work rate (the amount of energy being expended to cycle) was assessed at weeks 1 and 13. The change in maximum work measured during CPET between weeks 1 and 13 is reported.


Secondary Outcome Measures :
  1. Cystic Fibrosis Quality of Life-Revised Respiratory Domain Score [ Time Frame: Assessed at weeks 1 and 13 ]
    The CFQ-R Respiratory domain score (scale 0-100 with higher scores indicating better quality of life) was assessed at weeks 1 and 13. The change in the score between week 1 and week 13 is reported.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Confirmed diagnosis of CF based on the following criteria: Positive sweat chloride ≥60mEq/liter (by pilocarpine iontophoresis) and/or Genotype with two identifiable mutations consistent with CF, and accompanied by one or more clinical features consistent with the CF phenotype
  2. Male or female patients ≥ 18 years of age
  3. FEV1 ≥ 20% predicted and ≤ 70% predicted (Hankinson)
  4. Clinically stable without evidence of acute upper or lower respiratory tract infection or current pulmonary exacerbation within the 14 days prior to the screening visit
  5. Ability to reproducibly perform spirometry (according to ATS criteria)
  6. Ability to understand and sign a written informed consent or assent and comply with the requirements of the study
  7. Willingness to maintain chronic CF medication schedule (e.g. alternating month inhaled antibiotics)

Exclusion Criteria:

  1. History of hypersensitivity to sildenafil
  2. Use of an investigational agent within the 4-week period prior to Visit 1 (Day 0)
  3. Breastfeeding, pregnant, or verbal expression of unwillingness to practice an acceptable birth control method (abstinence, hormonal or barrier methods, partner sterilization or intrauterine device) during participation in the study for women of child-bearing potential.
  4. History of significant hepatic disease (AST or ALT > 5 times the upper limit of normal at screening, documented biliary cirrhosis, or portal hypertension),
  5. History of significant cardiovascular disease (history of aortic stenosis, coronary artery disease, or life-threatening arrhythmia),
  6. History of severe neurological disease (e.g. history of stroke),
  7. History of severe hematologic disease (e.g. history of bleeding diathesis; current INR > 2.0
  8. History of severe ophthalmologic disease (e.g. history of retinal impairment or non-arteritic ischemic optic neuritis)
  9. History of severe renal impairment (creatinine >1.8 mg/dL.)
  10. Inability to swallow pills
  11. Previous organ transplantation
  12. Use of concomitant nitrates, α-blocker, or Ca channel blocker (currently or within one month of Visit 1)
  13. Use of concomitant medications known to be potent inhibitors of CYP3A4 [e.g. ketoconazole, itraconazole, ritonavir, clarithromycin, erythromycin, rifampin (currently or within one month of initiation of study drug)] NOTE: use of azithromycin is NOT a cause for exclusion
  14. History of sputum or throat swab culture yielding Burkholderia cepacia or Mycobacterium massiliense within 2 years of screening
  15. Weight less than 40 kg at Screening
  16. History of migraine headaches.
  17. Resting room air oxygen saturation <80% without supplemental oxygen
  18. Presence of a condition or abnormality that in the opinion of the investigator would compromise the safety of the subject or the quality of the data
  19. Start of CFTR modulator therapy less than 1 month prior to first dose of sildenafil or placebo
  20. Use of anticoagulants
  21. Frank pulmonary hypertension (RVSP >40 mmHg by ECHO)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02626182


Locations
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United States, Colorado
National Jewish Health
Denver, Colorado, United States, 80206
Sponsors and Collaborators
National Jewish Health
Investigators
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Principal Investigator: Jennifer L Taylor-Cousar, MD National Jewish Health
  Study Documents (Full-Text)

Documents provided by Jennifer Taylor-Cousar, National Jewish Health:
Publications:

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Responsible Party: Jennifer Taylor-Cousar, Associate Professor, National Jewish Health
ClinicalTrials.gov Identifier: NCT02626182    
Other Study ID Numbers: NationalJewishHealth
First Posted: December 10, 2015    Key Record Dates
Results First Posted: July 15, 2019
Last Update Posted: July 24, 2019
Last Verified: July 2019
Additional relevant MeSH terms:
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Cystic Fibrosis
Vascular Diseases
Fibrosis
Pathologic Processes
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Cardiovascular Diseases
Sildenafil Citrate
Vasodilator Agents
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Urological Agents