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

NCT00872170 | Completed Phase 2 Results DMC

• 2 other identifiers: 638U01HL065238
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

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.

Conditions

Thalassemia; Hypertension, Pulmonary

Keywords

Pulmonary Hypertension

Outcome Measures

Primary Outcomes (1)

• Change in Six-minute Walk Test (6MWT) Distance From Baseline to Week 12 Among Sildenafil Group

  Change in six-minute walk test (6MWT) distance was calculated as 6MWT at week 12 minus 6MWT at baseline.

  Baseline and Week 12

Secondary Outcomes (10)

• Change in Tricuspid Regurgitant Jet Velocity (TRV) From Baseline to Week 12 Among Sildenafil Group

  Baseline and Week 12

• Change in Echo Left Ventricular End Systolic Volume (LVESV) From Baseline to Week 12 Among Sildenafil Group

  Baseline and Week 12

• Change in Echo Left Ventricular End Diastolic Volume (LVEDV) From Baseline to Week 12 Among Sildenafil Group

  Baseline and Week 12

• Change in Plasma Arginine From Baseline to Week 12 Among Sildenafil Group

  Baseline and Week 12

• Change in Red Blood Cell (RBC) Arginine From Baseline to Week 12 Among Sildenafil Group

  Baseline and Week 12

Study Arms (2)

Intervention

ACTIVE COMPARATOR

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

Drug: Sildenafil

Control

NO INTERVENTION

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

Interventions

Sildenafil 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

Also known as: Revatio, Viagra

Intervention

Eligibility Criteria

• Age: 7 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Pregnant or breastfeeding
• Hypersensitivity to arginine or sildenafil, based on prior use
• Any of the following medical conditions:
• Severe kidney insufficiency, defined as use of hemodialysis or serum creatinine at levels greater than 2.5 mg/dL at the time of screening
• Cardiac disease with adjustment of cardiac medications in the 60 days before study entry
• 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
• Stroke, defined as a new focal neurological deficit lasting more than 24 hours in the 45 days before study entry
• New diagnosis of pulmonary embolism by ventilation-perfusion scan, angiography, or any other technique in the 90 days before study entry
• History of retinal detachment or retinal hemorrhage in the 180 days before study entry
• Use of nitrate-based vasodilators, prostacyclin (inhaled, subcutaneous, or intravenous), endothelin antagonists, or any other medication for pulmonary hypertension
• Acute asthma exacerbation requiring use of prednisone in the 60 days before study entry
• Initiation or dosage increase of calcium channel blockers in the 30 days before study entry
• 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)

Sponsors & Collaborators

• Carelon Research: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Children's Hospital and Research Institute Oakland

Oakland, California, 94609, United States

Location

Related Publications (1)

• 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.

  PMID: 23585527 RESULT

MeSH Terms

Conditions

Thalassemia; Hypertension, Pulmonary

Interventions

Sildenafil Citrate

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Limitations and Caveats

Of 14 patients in the Sildenafil arm, 4 patients with discrepant TRVs between the local site, core lab and NHLBI readings were excluded for the main analyses.

Results Point of Contact

• Title: Nancy Gee
• Organization: New England Research Institutes

ngee@neriscience.com

617-972-3295

Study Officials

• Ellis Neufeld, MD, PhD

  Boston Children's Hospital

  PRINCIPAL INVESTIGATOR

• Claudia Morris, MD

  Children's Hospital and Research Institute Oakland

  STUDY CHAIR

• Charles Quinn, MD

  University of Texas, Southwestern Medical Center at Dallas

  PRINCIPAL INVESTIGATOR

• Patricia Giardina, MD

  Weill Medical College of Cornell

  PRINCIPAL INVESTIGATOR

• Janet Kwiatkowski, MD

  Children's Hospital of Philadelphia

  PRINCIPAL INVESTIGATOR

• Nancy Olivieri, MD

  Toronto General Hospital

  PRINCIPAL INVESTIGATOR

• John Porter, MD

  University College, London

  PRINCIPAL INVESTIGATOR

• Ali Taher, MD

  American University of Beirut Medical Center- Lebannon

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 30, 2009
• First Posted: March 31, 2009
• Study Start: March 1, 2009
• Primary Completion: June 1, 2010
• Study Completion: November 1, 2010
• Last Updated: February 21, 2014
• Results First Posted: February 21, 2014

Record last verified: 2014-01

Locations

US (1)