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| ID | Type | Description | Link |
|---|---|---|---|
| U01HL065238 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Intervention | Active Comparator | Participants with thalassemia who have pulmonary hypertension will receive sildenafil for 12 weeks. |
|
| 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Tricuspid Regurgitant Jet Velocity (TRV) From Baseline to Week 12 Among Sildenafil Group | Change in tricuspid regurgitant jet velocity (TRV) was calculated as TRV at week 12 minus TRV at baseline. The TRV provides an estimate of pulmonary artery pressure. | Baseline and Week 12 |
| Change in Echo Left Ventricular End Systolic Volume (LVESV) From Baseline to Week 12 Among Sildenafil Group |
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Inclusion Criteria for All Participants:
Inclusion Criteria for Participants with Pulmonary Hypertension:
Inclusion Criteria for Participants without Pulmonary Hypertension:
Exclusion Criteria:
Pregnant or breastfeeding
Hypersensitivity to arginine or sildenafil, based on prior use
Any of the following medical conditions:
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)
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| Name | Affiliation | Role |
|---|---|---|
| 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 |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Children's Hospital and Research Institute Oakland | Oakland | California | 94609 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23585527 | Result | 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Sildenafil | Participants with thalassemia who have pulmonary hypertension received sildenafil for 12 weeks. Sildenafil : Participants received 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 |
| FG001 | Control | Participants with thalassemia who do not have pulmonary hypertension were part of a control group and were only undergoing screening/baseline assessments. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
All 27 patients (14 in the Sildenafil group and 13 in the control group) who completed the baseline visit were used.
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| ID | Title | Description |
|---|---|---|
| BG000 | Sildenafil | Participants with thalassemia who have pulmonary hypertension received sildenafil for 12 weeks. Sildenafil : Participants received 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 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Of 14 patients in the Sildenafil arm, 4 patients with discrepant Tricuspid Regurgitant Jet Velocity (TRV) measurements between the local site, core lab and NHLBI readings and 2 patients who had no 6MWT at 12 weeks were excluded. Patients in control group were only assessed at baseline. Therefore, 8 Sildenafil and 0 control patients were used. | Posted | Mean | Standard Error | meters | Baseline and Week 12 |
|
up to Week 12
At each follow-up visit, Sildenafil patients were interviewed for medical conditions, medical changes, and symptoms that have occurred since the last visit. An Adverse Event (AE) form was completed if any AE was reported. A Serious Adverse Event form was completed for all AEs rated as serious. No AEs were collected for the control group.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Sildenafil | Participants with thalassemia who have pulmonary hypertension received sildenafil for 12 weeks. Sildenafil : Participants received 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 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Vision/color disturbance | Eye disorders |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Fatigue | General disorders |
|
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Nancy Gee | New England Research Institutes | 617-972-3295 | ngee@neriscience.com |
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| ID | Term |
|---|---|
| D013789 | Thalassemia |
| D006976 | Hypertension, Pulmonary |
| ID | Term |
|---|---|
| D000745 | Anemia, Hemolytic, Congenital |
| D000743 | Anemia, Hemolytic |
| D000740 | Anemia |
| D006402 | Hematologic Diseases |
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| ID | Term |
|---|---|
| D000068677 | Sildenafil Citrate |
| ID | Term |
|---|---|
| D013449 | Sulfonamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D013450 | Sulfones |
| D013457 |
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|
|
Change in echo left ventricular end systolic volume (LVESV) was calculated as LVESV at week 12 minus LVESV at baseline. |
| Baseline and Week 12 |
| Change in Echo Left Ventricular End Diastolic Volume (LVEDV) From Baseline to Week 12 Among Sildenafil Group | Change in echo left ventricular end diastolic volume (LVEDV) was calculated as LVEDV at week 12 minus LVEDV at baseline. | Baseline and Week 12 |
| Change in Plasma Arginine From Baseline to Week 12 Among Sildenafil Group | Change in Plasma Arginine was calculated as Plasma Arginine at week 12 minus Plasma Arginine at baseline. | Baseline and Week 12 |
| Change in Red Blood Cell (RBC) Arginine From Baseline to Week 12 Among Sildenafil Group | Change in Red Blood Cell (RBC) Arginine was calculated as Red Blood Cell (RBC) Arginine at week 12 minus Red Blood Cell (RBC) Arginine at baseline. | Baseline and Week 12 |
| Change in Soluble Platelet Selectin (sP-SELECTIN) From Baseline to Week 12 Among Sildenafil Group | Change in Soluble platelet selectin (sP-SELECTIN) was calculated as sP-SELECTIN at week 12 minus sP-SELECTIN at baseline. | Baseline and Week 12 |
| Change in Lactate Dehydrogenase (LDH) From Baseline to Week 12 Among Sildenafil Group | Change in Lactate dehydrogenase (LDH) was calculated as LDH at week 12 minus LDH at baseline. | Baseline and Week 12 |
| Change in Cell Free Hemoglobin From Baseline to Week 12 Among Sildenafil Group | Change in Cell Free Hemoglobin was calculated as Cell Free Hemoglobin at week 12 minus Cell Free Hemoglobin at baseline. | Baseline and Week 12 |
| Change in Arginase Concentration From Baseline to Week 12 Among Sildenafil Group | Change in Arginase concentration was calculated as Arginase concentration at week 12 minus Arginase concentration at baseline. | Baseline and Week 12 |
| Change in Arginase Activity From Baseline to Week 12 Among Sildenafil Group | Change in Arginase activity was calculated as Arginase activity at week 12 minus Arginase activity at baseline. | Baseline and Week 12 |
| BG001 | Control | Participants with thalassemia who do not have pulmonary hypertension were part of a control group and were only undergoing screening/baseline assessments. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
|
|
|
| Secondary | Change in Tricuspid Regurgitant Jet Velocity (TRV) From Baseline to Week 12 Among Sildenafil Group | Change in tricuspid regurgitant jet velocity (TRV) was calculated as TRV at week 12 minus TRV at baseline. The TRV provides an estimate of pulmonary artery pressure. | Of 14 patients in the Sildenafil arm, 4 patients with discrepant Tricuspid Regurgitant Jet Velocity (TRV) measurements between the local site, core lab and NHLBI readings and one patient who withdrew from the study were excluded. Patients in control group were only assessed at baseline. Therefore, 9 Sildenafil and 0 control patients were used. | Posted | Mean | Standard Error | m/s | Baseline and Week 12 |
|
|
|
|
| Secondary | Change in Echo Left Ventricular End Systolic Volume (LVESV) From Baseline to Week 12 Among Sildenafil Group | Change in echo left ventricular end systolic volume (LVESV) was calculated as LVESV at week 12 minus LVESV at baseline. | Of 14 patients in the Sildenafil arm, 4 patients with discrepant Tricuspid Regurgitant Jet Velocity (TRV) measurements between the local site, core lab and NHLBI readings and one patient who withdrew from the study were excluded. Patients in control group were only assessed at baseline. Therefore, 9 Sildenafil and 0 control patients were used. | Posted | Mean | Standard Error | ml | Baseline and Week 12 |
|
|
|
|
| Secondary | Change in Echo Left Ventricular End Diastolic Volume (LVEDV) From Baseline to Week 12 Among Sildenafil Group | Change in echo left ventricular end diastolic volume (LVEDV) was calculated as LVEDV at week 12 minus LVEDV at baseline. | Of 14 patients in the Sildenafil arm, 4 patients with discrepant Tricuspid Regurgitant Jet Velocity (TRV) measurements between the local site, core lab and NHLBI readings and one patient who withdrew from the study were excluded. Patients in control group were only assessed at baseline. Therefore, 9 Sildenafil and 0 control patients were used. | Posted | Mean | Standard Error | ml | Baseline and Week 12 |
|
|
|
|
| Secondary | Change in Plasma Arginine From Baseline to Week 12 Among Sildenafil Group | Change in Plasma Arginine was calculated as Plasma Arginine at week 12 minus Plasma Arginine at baseline. | Of 14 patients in the Sildenafil arm, 4 patients with discrepant Tricuspid Regurgitant Jet Velocity (TRV) measurements between the local site, core lab and NHLBI readings and one patient who withdrew from the study were excluded. Patients in control group were only assessed at baseline. Therefore, 9 Sildenafil and 0 control patients were used. | Posted | Mean | Standard Error | µM | Baseline and Week 12 |
|
|
|
|
| Secondary | Change in Red Blood Cell (RBC) Arginine From Baseline to Week 12 Among Sildenafil Group | Change in Red Blood Cell (RBC) Arginine was calculated as Red Blood Cell (RBC) Arginine at week 12 minus Red Blood Cell (RBC) Arginine at baseline. | Of 14 patients in the Sildenafil arm, 4 patients with discrepant Tricuspid Regurgitant Jet Velocity (TRV) measurements between the local site, core lab and NHLBI readings and one patient who withdrew from the study were excluded. Patients in control group were only assessed at baseline. Therefore, 9 Sildenafil and 0 control patients were used. | Posted | Mean | Standard Error | µM | Baseline and Week 12 |
|
|
|
|
| Secondary | Change in Soluble Platelet Selectin (sP-SELECTIN) From Baseline to Week 12 Among Sildenafil Group | Change in Soluble platelet selectin (sP-SELECTIN) was calculated as sP-SELECTIN at week 12 minus sP-SELECTIN at baseline. | Of 14 patients in the Sildenafil arm, 4 patients with discrepant Tricuspid Regurgitant Jet Velocity (TRV) measurements between the local site, core lab and NHLBI readings and one patient who withdrew from the study were excluded. Patients in control group were only assessed at baseline. Therefore, 9 Sildenafil and 0 control patients were used. | Posted | Mean | Standard Error | ng/ml | Baseline and Week 12 |
|
|
|
|
| Secondary | Change in Lactate Dehydrogenase (LDH) From Baseline to Week 12 Among Sildenafil Group | Change in Lactate dehydrogenase (LDH) was calculated as LDH at week 12 minus LDH at baseline. | Of 14 patients in the Sildenafil arm, 4 patients with discrepant Tricuspid Regurgitant Jet Velocity (TRV) measurements between the local site, core lab and NHLBI readings and 2 patients who had no LDH at 12 weeks were excluded. Patients in control group were only assessed at baseline. Therefore, 8 Sildenafil and 0 control patients were used. | Posted | Mean | Standard Error | U/L | Baseline and Week 12 |
|
|
|
|
| Secondary | Change in Cell Free Hemoglobin From Baseline to Week 12 Among Sildenafil Group | Change in Cell Free Hemoglobin was calculated as Cell Free Hemoglobin at week 12 minus Cell Free Hemoglobin at baseline. | Of 14 patients in the Sildenafil arm, 4 patients with discrepant Tricuspid Regurgitant Jet Velocity (TRV) measurements between the local site, core lab and NHLBI readings and one patient who withdrew from the study were excluded. Patients in control group were only assessed at baseline. Therefore, 9 Sildenafil and 0 control patients were used. | Posted | Mean | Standard Error | ug/ml | Baseline and Week 12 |
|
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|
|
| Secondary | Change in Arginase Concentration From Baseline to Week 12 Among Sildenafil Group | Change in Arginase concentration was calculated as Arginase concentration at week 12 minus Arginase concentration at baseline. | Of 14 patients in the Sildenafil arm, 4 patients with discrepant Tricuspid Regurgitant Jet Velocity (TRV) measurements between the local site, core lab and NHLBI readings and one patient who withdrew from the study were excluded. Patients in control group were only assessed at baseline. Therefore, 9 Sildenafil and 0 control patients were used. | Posted | Mean | Standard Error | ng/ml | Baseline and Week 12 |
|
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|
|
| Secondary | Change in Arginase Activity From Baseline to Week 12 Among Sildenafil Group | Change in Arginase activity was calculated as Arginase activity at week 12 minus Arginase activity at baseline. | Of 14 patients in the Sildenafil arm, 4 patients with discrepant Tricuspid Regurgitant Jet Velocity (TRV) measurements between the local site, core lab and NHLBI readings and one patient who withdrew from the study were excluded. Patients in control group were only assessed at baseline. Therefore, 9 Sildenafil and 0 control patients were used. | Posted | Mean | Standard Error | U/L | Baseline and Week 12 |
|
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|
|
| 2 |
| 14 |
| 11 |
| 14 |
| EG001 | Control | Participants with thalassemia who do not have pulmonary hypertension were part of a control group and were only undergoing screening/baseline assessments. | 0 | 0 | 0 | 0 |
| Dyspnea | Respiratory, thoracic and mediastinal disorders |
|
| Photophobia | Eye disorders |
|
| Headache | Nervous system disorders |
|
| Vision/color disturbance | Eye disorders |
|
| Hemoglobin decreased | Blood and lymphatic system disorders |
|
| Edema limbs | General disorders |
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| Dizziness | General disorders |
|
| Back pain | Musculoskeletal and connective tissue disorders |
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| Pain-other: sciatic pain of left leg with associated back pain | Musculoskeletal and connective tissue disorders |
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| INR increased | Hepatobiliary disorders |
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| Phlebitis | Injury, poisoning and procedural complications |
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| Vision blurred | Eye disorders |
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| Ocular/visual - other (shining outline on objects) | Eye disorders |
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| Prolonged erection (priapism) | Reproductive system and breast disorders |
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| Dyspnea | Respiratory, thoracic and mediastinal disorders |
|
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| D006425 |
| Hemic and Lymphatic Diseases |
| D006453 | Hemoglobinopathies |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D006973 | Hypertension |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| Sulfur Compounds |
| D010879 | Piperazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |