NCT00352430

Cardiopulmonary Function Assessment and NO-Based Therapies for Patients With Hemolysis-Associated Pulmonary Hypertension

Completed Phase 1 Last updated 25 September 2019

What this trial tests

Phase 1 trial testing Nitric Oxide/INP Pulse Delivery in Pulmonary Hypertension in 31 participants. Completed in 10 March 2010.

Timeline

9 July 2006

Primary endpoint
10 March 2010

10 March 2010

Quick facts

Lead sponsor	National Heart, Lung, and Blood Institute (NHLBI)
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Primary purpose	treatment
Enrollment	31
Start date	9 July 2006
Primary completion	10 March 2010
Estimated completion	10 March 2010
Sites	1 location across United States

Drugs / interventions tested

• Nitric Oxide/INP Pulse Delivery — full drug profile →
• Nitric Oxide/INO Pulse Delivery — full drug profile →

Conditions studied

• Pulmonary Hypertension — all drugs for Pulmonary Hypertension →

Sponsor

National Heart, Lung, and Blood Institute (NHLBI)

Who can join

18 and older, any sex, with Pulmonary Hypertension. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

This study will evaluate new treatments for people who have pulmonary hypertension, or high blood pressure in the lungs, caused by sickle cell anemia or thalassemia.

Patients ages 18 and older with a diagnosis of sickle cell disease or thalassemia, who have mild to severe pulmonary hypertension, and who are not pregnant or breastfeeding may be eligible for this study. There are three stages in the study, with up to 200 participants in the screening. Patients will undergo pulmonary function tests, including those for asthma and measurement of oxygen levels in the arterial blood. They will have a chest X-ray, computed tomography (CT) scan of the lungs, ventilation perfusion lung scan to look for blood clots, echocardiogram, test to measure how far patients can walk in 6 minutes, nighttime oxygen measurement done while asleep, blood collection, magnetic resonance imaging (MRI) scan of the heart, and exercise test. About 3 to 4 days are needed for the tests, all of which can be done while patients are outpatients, except for the sleep study. For the CT scan, patients lie on a table while an X-ray beam takes images of the lungs and heart. The lung scan involves breathing of a small amount of a radioactive aerosol called Tc99m DTPA while pictures are taken of the lungs from various angles. Then an injection of albumin, a protein with a small amount of radioactivity, will be given, and more lung pictures will be taken. For the MRI scan, patients lie on a table that slides into a machine. A medication called gadolinium will be injected, to help improve images made through the scan. After the tests, patients will be admitted to the Clinical Center for 1 day. A small plastic catheter, or tube, will be placed in the vein of an arm. A longer catheter will go into a deeper vein (neck or leg), and a pulmonary artery catheter will be inserted to measure blood pressure in the blood vessels. Doctors will guide the catheter into the lung artery. Patients will be asked to pedal on a stationary bicycle while heart and lung pressure is measured. If pulmonary hypertension is present, patients will proceed to the second stage (up to 50 participants). While the catheter is still in place, patients will wear a face mask and breathe nitric oxide (NO) for 20 minutes. They will take 50 mg of sildenafil by mouth, and pressure in the heart and lungs will be monitored for about 4 hours. They will again receive NO for another 20 minutes. Blood samples will be taken, and the heart rhythm and pressure in the lungs will be monitored. Sildenafil can cause headache, flushing, and indigestion. Side effects of the lung scan involve allergic reactions to DTPA and albumin. Patients with an allergy to eggs should not have that test.

Up to 25 patients can enter the third stage. They will breathe NO by using a tank of gas that delivers it through tubes to the nose, for a period of 6 weeks. They will continue taking sildenafil as previously prescribed and visit the clinic every 2 to 4 weeks for an echocardiogram, blood tests, and 6-minute walk test. After 6 weeks, patients will have catheterization of the heart again to measure pressure in the heart and lungs. Then NO will be stopped, and pressure in the lungs will be checked to see if NO has helped lower the blood pressure-and to make sure that the blood pressure does not increase when medication is stopped. Patients whose symptoms have improved as a result of breathing NO may wish to continue with that therapy.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Platelet activation in patients with sickle disease, hemolysis-associated pulmonary hypertension, and nitric oxide scavenging by cell-free hemoglobin.
   Villagra J, Shiva S, Hunter LA, Machado RF, et al · · 2007 · cited 271× · PMID 17536019 · DOI 10.1182/blood-2006-12-061697
2. Hemodynamic predictors of mortality in adults with sickle cell disease.
   Mehari A, Alam S, Tian X, Cuttica MJ, et al · · 2013 · cited 98× · PMID 23348978 · DOI 10.1164/rccm.201207-1222oc
3. Endothelin receptor antagonists for pulmonary hypertension in adult patients with sickle cell disease.
   Minniti CP, Machado RF, Coles WA, Sachdev V, et al · · 2009 · cited 55× · PMID 19775299 · DOI 10.1111/j.1365-2141.2009.07906.x
4. Heme-bound iron activates placenta growth factor in erythroid cells via erythroid Krüppel-like factor.
   Wang X, Mendelsohn L, Rogers H, Leitman S, et al · · 2014 · cited 39× · PMID 24916507 · DOI 10.1182/blood-2013-11-539718
5. Pharmacotherapy in sickle cell disease--state of the art and future prospects.
   Hankins J, Aygun B. · · 2009 · cited 18× · PMID 19222472 · DOI 10.1111/j.1365-2141.2009.07602.x
6. Abnormal Ventilation-Perfusion Scan Is Associated with Pulmonary Hypertension in Sickle Cell Adults.
   Mehari A, Igbineweka N, Allen D, Nichols J, et al · · 2019 · cited 12× · PMID 29880507 · DOI 10.2967/jnumed.118.211466
7. Elevated transpulmonary gradient and cardiac magnetic resonance-derived right ventricular remodeling predict poor outcomes in sickle cell disease.
   Nguyen KL, Tian X, Alam S, Mehari A, et al · · 2016 · cited 9× · PMID 26589907 · DOI 10.3324/haematol.2015.125229
8. Nitric oxide-based multi-synergistic nanomedicine: an emerging therapeutic for anticancer.
   Tang Y, Li Q, Zhou Z, Bai H, et al · · 2024 · cited 8× · PMID 39497134 · DOI 10.1186/s12951-024-02929-z