Sildenafil to Improve Exercise Capacity in People With Thalassemia and Pulmonary Hypertension

NCT ID: NCT00872170

Last Updated: 2014-02-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 27 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-03-31
• Study Completion Date: 2010-11-30

Brief Summary

Thalassemia is an inherited blood disorder that can result in mild to severe anemia. Many people with thalassemia also have pulmonary hypertension, which is high blood pressure in the arteries in the lungs. This study will evaluate the safety and effectiveness of the medication sildenafil at reducing blood pressure in the lungs of people with thalassemia and pulmonary hypertension.

Detailed Description

Thalassemia is an inherited blood disorder in which the body makes an abnormal form of hemoglobin-the protein in red blood cells that carries oxygen. A potential complication of thalassemia is pulmonary hypertension, which is a condition characterized by abnormally high blood pressure in the arteries of the lungs. People with thalassemia who have pulmonary hypertension tend to experience more health complications, including shortness of breath and a reduced exercise capacity, than people with thalassemia who do not have pulmonary hypertension. Sildenafil is a medication that is used to treat pulmonary hypertension; however, it has not yet been studied in people with thalassemia. The purpose of this study is to evaluate the safety and effectiveness of sildenafil at reducing blood pressure in the lungs of people who have thalassemia and pulmonary hypertension. Study researchers will also further compare the differences between people with thalassemia who have pulmonary hypertension and those who do not have pulmonary hypertension.

This study will enroll people with thalassemia who have pulmonary hypertension and a control group of people with thalassemia who do not have pulmonary hypertension. People with thalassemia and pulmonary hypertension will attend a baseline study visit at which time they will undergo the following procedures: medical history and medical record review; physical exam; a 6-minute walk test, which will measure how far participants can walk in 6 minutes; an echocardiogram to obtain images of the heart; blood collection; and for females, a urine collection. Participants will then begin taking sildenafil three times a day for 12 weeks. At study visits at Weeks 2, 4, and 8, participants will undergo repeat baseline testing, and some participants will take part in an exhaled nitric oxide test. At Week 12, participants will also undergo lung function testing and a chest magnetic resonance imaging (MRI) procedure.

Participants in the control group will attend one to three study visits at baseline, which will include the same baseline study procedures listed above, plus lung function testing, a chest MRI, a chest computed tomography (CAT) scan, and exhaled nitric oxide testing. They will not receive any medication or have any further study visits.

Conditions

Thalassemia; Hypertension, Pulmonary

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Intervention

Participants with thalassemia who have pulmonary hypertension will receive sildenafil for 12 weeks.

Group Type: ACTIVE_COMPARATOR

Sildenafil

Intervention Type: DRUG

Participants will receive sildenafil for 12 weeks with the following therapy:

50 mg of oral sildenafil three times a day (TID) increased to 100 mg TID as tolerated in adults and children greater than 50 kg; 1 mg/kg sildenafil TID without dose escalation in children less than 50 kg

Control

Participants with thalassemia who do not have pulmonary hypertension will be part of a control group and will only be undergoing screening/baseline assessments.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Sildenafil

Participants will receive sildenafil for 12 weeks with the following therapy:

50 mg of oral sildenafil three times a day (TID) increased to 100 mg TID as tolerated in adults and children greater than 50 kg; 1 mg/kg sildenafil TID without dose escalation in children less than 50 kg

Intervention Type: DRUG

Other Intervention Names

Revatio; Viagra

Eligibility Criteria

Inclusion Criteria

• Alpha, beta, or E-beta thalassemia confirmed by hemoglobin (Hb)-electrophoresis or molecular diagnosis

• Pulmonary hypertension, defined as a tricuspid regurgitant jet (TRjet) velocity by Doppler echocardiography greater than 2.5 m/s

• Lack of pulmonary hypertension, defined as TRjet velocity by Doppler echocardiography less than 2.5 m/s

Exclusion Criteria

• Pregnant or breastfeeding
• Hypersensitivity to arginine or sildenafil, based on prior use
• Any of the following medical conditions:

1. Severe kidney insufficiency, defined as use of hemodialysis or serum creatinine at levels greater than 2.5 mg/dL at the time of screening

2. Cardiac disease with adjustment of cardiac medications in the 60 days before study entry

3. Symptomatic coronary artery disease, as indicated by a history of chest pain, angina, claudication, or surgery to treat coronary artery disease in the 1 year before study entry

4. Stroke, defined as a new focal neurological deficit lasting more than 24 hours in the 45 days before study entry

5. New diagnosis of pulmonary embolism by ventilation-perfusion scan, angiography, or any other technique in the 90 days before study entry

6. History of retinal detachment or retinal hemorrhage in the 180 days before study entry

7. Use of nitrate-based vasodilators, prostacyclin (inhaled, subcutaneous, or intravenous), endothelin antagonists, or any other medication for pulmonary hypertension

8. Acute asthma exacerbation requiring use of prednisone in the 60 days before study entry

9. Initiation or dosage increase of calcium channel blockers in the 30 days before study entry

10. Initiation of any other cardiac or pulmonary medication in the 90 days before study entry

• Presence of any other condition, which in the opinion of the investigator, would make the person unsuitable for enrollment or could interfere with compliance in the study, including but not limited to alcohol or drug abuse
• No measurable TRjet on Doppler echocardiography (i.e., presence of pulmonary hypertension cannot be confirmed or ruled out)

• Minimum Eligible Age: 7 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Carelon Research

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ellis Neufeld, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Boston Children's Hospital

Claudia Morris, MD

Role: STUDY_CHAIR

Children's Hospital and Research Institute Oakland

Charles Quinn, MD

Role: PRINCIPAL_INVESTIGATOR

University of Texas, Southwestern Medical Center at Dallas

Patricia Giardina, MD

Role: PRINCIPAL_INVESTIGATOR

Weill Medical College of Cornell

Janet Kwiatkowski, MD

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital of Philadelphia

Nancy Olivieri, MD

Role: PRINCIPAL_INVESTIGATOR

Toronto General Hospital

John Porter, MD

Role: PRINCIPAL_INVESTIGATOR

University College, London

Ali Taher, MD

Role: PRINCIPAL_INVESTIGATOR

American University of Beirut Medical Center- Lebannon

Locations

Children's Hospital and Research Institute Oakland

Oakland, California, United States

Countries

United States

References

Morris CR, Kim HY, Wood J, Porter JB, Klings ES, Trachtenberg FL, Sweeters N, Olivieri NF, Kwiatkowski JL, Virzi L, Singer ST, Taher A, Neufeld EJ, Thompson AA, Sachdev V, Larkin S, Suh JH, Kuypers FA, Vichinsky EP; Thalassemia Clinical Research Network. Sildenafil therapy in thalassemia patients with Doppler-defined risk of pulmonary hypertension. Haematologica. 2013 Sep;98(9):1359-67. doi: 10.3324/haematol.2012.082065. Epub 2013 Apr 12.

Reference Type: RESULT

PMID: 23585527 (View on PubMed)

Other Identifiers

U01HL065238

Identifier Type: NIH

Identifier Source: secondary_id

View Link

638

Identifier Type: -

Identifier Source: org_study_id