Phase 3
N=27
Sildenafil to Improve Exercise Capacity in People With Thalassemia and Pulmonary Hypertension
Thalassemia · Hypertension, Pulmonary
Bottom Line
View on ClinicalTrials.gov: NCT00872170 ↗Enrolled (actual)
27
Serious AEs
14.3%
Results posted
Feb 2014
Primary outcome: Primary: Change in Six-minute Walk Test (6MWT) Distance From Baseline to Week 12 Among Sildenafil Group — -1.38 meters — p=0.97
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Sildenafil (Drug)
- Age
- Pediatric, Adult, Older Adult · 7+ yrs
- Sex
- All
- Sponsor
- Carelon Research
- Primary completion
- Jun 2010
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change in Six-minute Walk Test (6MWT) Distance From Baseline to Week 12 Among Sildenafil Group |
-1.38 | 0.97 |
| SECONDARY Change in Tricuspid Regurgitant Jet Velocity (TRV) From Baseline to Week 12 Among Sildenafil Group |
-0.45 | 0.04 sig |
| SECONDARY Change in Echo Left Ventricular End Systolic Volume (LVESV) From Baseline to Week 12 Among Sildenafil Group |
-3.82 | 0.005 sig |
| SECONDARY Change in Echo Left Ventricular End Diastolic Volume (LVEDV) From Baseline to Week 12 Among Sildenafil Group |
-7.89 | 0.02 sig |
| SECONDARY Change in Plasma Arginine From Baseline to Week 12 Among Sildenafil Group |
31.77 | 0.05 |
| SECONDARY Change in Red Blood Cell (RBC) Arginine From Baseline to Week 12 Among Sildenafil Group |
3.67 | 0.02 sig |
| SECONDARY Change in Soluble Platelet Selectin (sP-SELECTIN) From Baseline to Week 12 Among Sildenafil Group |
121.13 | 0.04 sig |
| SECONDARY Change in Lactate Dehydrogenase (LDH) From Baseline to Week 12 Among Sildenafil Group |
23.37 | 0.33 |
| SECONDARY Change in Cell Free Hemoglobin From Baseline to Week 12 Among Sildenafil Group |
-67.60 | 0.18 |
| SECONDARY Change in Arginase Concentration From Baseline to Week 12 Among Sildenafil Group |
-17.06 | 0.97 |
| SECONDARY Change in Arginase Activity From Baseline to Week 12 Among Sildenafil Group |
0.33 | 0.96 |
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.
Eligibility Criteria
Inclusion Criteria for All Participants:
- Alpha, beta, or E-beta thalassemia confirmed by hemoglobin (Hb)-electrophoresis or molecular diagnosis
Inclusion Criteria for Participants with Pulmonary Hypertension:
- Pulmonary hypertension, defined as a tricuspid regurgitant jet (TRjet) velocity by Doppler echocardiography greater than 2.5 m/s
Inclusion Criteria for Participants without Pulmonary Hypertension:
- 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:
- 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)
Data sourced from ClinicalTrials.gov (NCT00872170). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.