Inhaled Nitric Oxide (iNO) in Post-Pulmonary Embolism (Post-PE)

• Status: Recruiting
• Trial end date: 2022-10-30
• Target enrollment: 0
• Participant gender: All

Summary

Following acute pulmonary embolism (PE), up to a third of patients develop post-PE syndrome described as having persistent breathlessness (dyspnea), impaired exercise capacity, and a reduced quality of life. The post-PE syndrome includes patients with chronic thromboembolic pulmonary hypertension (CTEPH), patients with chronic thromboembolic disease (CTED) those with an obstruction of the pulmonary arteries without pulmonary hypertension, and patients with post-PE related dyspnea without obstruction or pulmonary hypertension. Although therapies exist for the most severe form of the post-PE syndrome (CTEPH) - for most patients there are no available disease specific therapies that reduce symptoms. Despite studies showing increased breathlessness and abnormal exercise responses in patients with CTED, a detailed examination of what causes breathlessness in post-PE syndrome has never been undertaken. It is suspected that reduced blood flow to the lungs contributes to the feelings of breathlessness, particularly during exercise.

This study will use inhaled nitric oxide, a medication that increases blood flow to the lungs. Inhaled nitric oxide is used primarily in hospitalized patients in the intensive care unit with respiratory failure, its use in people with post-PE syndrome is experimental. The investigators believe use of this medication may help to relieve symptoms of breathlessness. In order to test this medication, in volunteers with post-PE syndrome, the following will be measured: 1) breathlessness, 2) the signal to breathe sent from the brain to the lungs, 3) the activity of the muscles involved with breathing and 4) the amount of different gasses in the blood during exercise. The investigators will compare breathlessness and exercise tolerance during exercise while receiving: 1) a placebo (normal medical grade air) and 2) inhaled nitric oxide (a medication that improves blood flow to the lungs). By comparing symptoms during these two conditions, it is hoped to obtain a better understanding of what causes breathlessness in people with post-PE syndrome. This clinical research study will recruit approximately 20 clinically stable participants with CTED or post-PE related breathlessness.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Queen's University
• Treatments: Nitric Oxide

Criteria

Inclusion Criteria:

1. clinically stable CTED or post-PE syndrome patients, as defined by stable hemodynamic status, optimized medical treatment, no changes in medication dosage or frequency of administration with no hospital admissions in the preceding 6 weeks;

2. a diagnosis of persistent, moderate to severe exertional dyspnea ≥ 6 months following PE as confirmed by study physician at time of enrollment by a modified Medical Research Council (mMRC) dyspnea scale =2, or Baseline Dyspnea Index (BDI) focal score <=6;

3. male or female non-pregnant adults >20 years of age;

4. ability to perform all study procedures

5. ability to provide informed consent

Exclusion Criteria:

1. women of childbearing potential who are pregnant or trying to become pregnant;

2. echocardiographic evidence of pulmonary hypertension

3. prior history of unstable pulmonary thromboembolism or systemic connective tissue vasculopathy,

4. active cardiopulmonary disease or other comorbidities that could contribute to dyspnea and exercise limitation;

5. history/clinical evidence of asthma, atopy and/or nasal polyps;

6. history of hypercapnic respiratory failure or a clinical diagnosis of sleep disordered breathing;

7. important contraindications to clinical exercise testing, including inability to exercise because of neuromuscular or musculoskeletal disease(s);

8. body mass index (BMI) <18.5 or ≥35.0 kg/m2;

9. use of daytime oxygen or exercise-induced O2 desaturation (<80% on room air).