Carbon Monoxide Therapy for Severe Pulmonary Arterial Hypertension

• Status: Withdrawn
• Trial end date: 2018-12-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to examine the potential of carbon monoxide (CO) to decrease elevated blood pressure in the pulmonary artery. This symptom is seen in patients with pulmonary arterial hypertension, a rare disease that causes fatigue, dizziness, and shortness of breath because the blood vessels that supply the lungs narrow, forcing the heart to work harder to push blood through. Previous studies in the laboratory have shown that carbon monoxide has promise in treating these symptoms.

Subjects in this study are being asked to undergo a new type of treatment to improve pulmonary arterial hypertension by breathing CO gas. CO is a colorless, tasteless, odorless gas usually found in car exhaust or cigarette smoke. It is administered with a continuous flow of air. Subjects will undergo a screening process during which it will be determined if they are eligible for the study. After the screening process, if subjects meet eligibility criteria for the study, they will begin carbon monoxide treatment through a cushioned mask that is placed over the nose and mouth. This treatment will last for sixteen weeks.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Illinois at Chicago
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); National Institutes of Health (NIH)
• Treatments: Carbon Monoxide

Criteria

Inclusion Criteria:

• male and female ≥ 18 years old , with Pulmonary Arterial Hypertension

• Right heart catheterization diagnosis of PAH:

• Mean Pulmonary Artery Pressure (mPAP)> 25 mmHg at rest

• Pulmonary Capillary Occlusion Pressure (PCOP) or Left Ventricular End Diastolic Pressure (LVEDP) < 15 mmHg

• Pulmonary Vascular Resistance (PVR) > 3 mmHg/L/min

• Must be Class 1.1, 1.2, or 1.3 PAH (see Appendix A)

• Echocardiographic evidence of Right Ventricular Dysfunction

• On standard and stable PAH therapy (no dose changes in the 4 weeks prior to starting the study medication) including:

• A Prostacyclin (IV epoprostenol, IV or subcutaneous remodulin, inhaled iloprost or remodulin) unless willing or unable to tolerate therapy AND

• Phosphodiesterase type 5 inhibitor OR

• Endothelin Receptor Antagonist OR

• Any combination of a-c

• NYHA class III or IV despite 3 months of stable therapy as outlined above

• 6 minute walk distance ≤ 380m

• Negative serum pregnancy test

• Female of childbearing age either surgically sterilized or using acceptable method of contraception. Acceptable methods of contraception include oral contraceptives, IUD, or other barrier methods of contraception.

Exclusion Criteria:

• History of malignancy in 2 years prior to enrollment

• Baseline cytopenia's:

• White blood cell count ≤ 3,000 i. Absolute Neutrophil Count (ANC) less than 1500 cells/mm3

• Hemoglobin ≤ 7

• Platelet ≤ 100,000

• Baseline Liver Disease:

• ALT/AST, ALk phos > 2.5x ULN, INR > 1.5

• Bilirubin > 1.5 x ULN

• Coronary artery disease

• Any cause of pulmonary hypertension other than class 1.1, 1.2, or 1.3 PAH.

• Baseline Renal Disease: Cr ≥ 2

• Active Smoker

• Hypoxemia with SaO2 < 95% on oxygen 2 L/min

• Baseline COHb > 2%

• Pregnancy or lactation

• Inability to attend scheduled clinic visits

• Previous lung transplant

• Naive to available standard PAH therapy

• Pulmonary Capillary Occlusion Pressure (PCOP) or LEft Ventricular End Diastolic Pressure (LVEDP)< 15 mmHg

• Concomitant enrollment in another investigational treatment protocol for PAH or taking any off label drug therapy for PAH

• Recent enrollment in or plans to enroll in Pulmonary Rehabilitation during the study period

• Any condition that in the opinion of the investigator would prevent completion of study procedures