ThalassemiaPhase 2/3NCT00872170
Sildenafil to Improve Exercise Capacity in People With Thalassemia and Pulmonary Hypertension
A Phase 2/3 study testing Sildenafil in people with Thalassemia and Hypertension, Pulmonary, run by Carelon Research at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 7 years and older
- Conditions the study is for
- Thalassemia, Hypertension, Pulmonary
- What is being tested?
- Sildenafil
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2009to Nov 2010
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 7 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 15Show fewer
- 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)
Trial locations and contacts
1 site in 1 country.
United States1 site
Children's Hospital and Research Institute Oakland
Oakland, California, 94609
About this study
Official title: Pilot of Oral Sildenafil for the Treatment of Pulmonary Hypertension in Thalassemia With Comparison to Controls
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.
Read the 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
- Being tested
- Sildenafil
- Keywords
- Pulmonary Hypertension
- Medical subject headings
- Thalassemia, Hypertension, Pulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SildenafilDrug
Also called Revatio, Viagra
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
| Study group | Role | What they receive |
|---|---|---|
| Intervention | Active comparator | Participants with thalassemia who have pulmonary hypertension will receive sildenafil for 12 weeks. Receives: 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline and Week 12
Secondary outcomes (10)
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.
Measured: Baseline and Week 12
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline and Week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Mar 2009 (estimated)
- Study startMar 2009
- Primary completionJun 2010
- Study completionNov 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for ThalassemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Carelon Research
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Sponsor
- Investigators
- Ellis Neufeld, MD, PhD, Principal investigator, Boston Children's HospitalClaudia Morris, MD, Study chair, Children's Hospital and Research Institute OaklandCharles Quinn, MD, Principal investigator, University of Texas, Southwestern Medical Center at DallasPatricia Giardina, MD, Principal investigator, Weill Medical College of CornellJanet Kwiatkowski, MD, Principal investigator, Children's Hospital of PhiladelphiaNancy Olivieri, MD, Principal investigator, Toronto General HospitalJohn Porter, MD, Principal investigator, University College, LondonAli Taher, MD, Principal investigator, American University of Beirut Medical Center- Lebannon
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00872170
- Sponsor's protocol ID
- 638
- Other IDs
- U01HL065238
- Status last verified
- Jan 2014
- First submitted
- 30 Mar 2009
- Last updated
- 21 Feb 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 23585527
Study at a glance
From the registry record, last updated by the sponsor on 21 Feb 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot of Oral Sildenafil for the Treatment of Pulmonary Hypertension in Thalassemia With Comparison to Controls
- ClinicalTrials.gov ID
- NCT00872170
- Acronym / sponsor ID
- 638
- Conditions
- Thalassemia, Hypertension, Pulmonary
- Keywords
- Pulmonary Hypertension
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Carelon ResearchUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Mar 2009
- Primary completion
- Jun 2010 (actual)
- Study completion
- Nov 2010 (actual)
- First posted
- 31 Mar 2009 (estimated)
- Results
- Posted 21 Feb 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intervention | Active comparator | Drug: SildenafilParticipants 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. |
Who may qualify
- Ages
- 7 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (15 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SildenafilAlso: Revatio, ViagraParticipants 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 | Drug | Intervention |
Primary outcome
Change in Six-minute Walk Test (6MWT) Distance From Baseline to Week 12 Among Sildenafil Group
Time frame: Baseline and Week 12
Change in six-minute walk test (6MWT) distance was calculated as 6MWT at week 12 minus 6MWT at baseline.
10 secondary outcomes
Change in Tricuspid Regurgitant Jet Velocity (TRV) From Baseline to Week 12 Among Sildenafil Group
Time frame: Baseline and Week 12
Change in Echo Left Ventricular End Systolic Volume (LVESV) From Baseline to Week 12 Among Sildenafil Group
Time frame: Baseline and Week 12
Change in Echo Left Ventricular End Diastolic Volume (LVEDV) From Baseline to Week 12 Among Sildenafil Group
Time frame: Baseline and Week 12
Change in Plasma Arginine From Baseline to Week 12 Among Sildenafil Group
Time frame: Baseline and Week 12
Change in Red Blood Cell (RBC) Arginine From Baseline to Week 12 Among Sildenafil Group
Time frame: Baseline and Week 12
Change in Soluble Platelet Selectin (sP-SELECTIN) From Baseline to Week 12 Among Sildenafil Group
Time frame: Baseline and Week 12
Change in Lactate Dehydrogenase (LDH) From Baseline to Week 12 Among Sildenafil Group
Time frame: Baseline and Week 12
Change in Cell Free Hemoglobin From Baseline to Week 12 Among Sildenafil Group
Time frame: Baseline and Week 12
Change in Arginase Concentration From Baseline to Week 12 Among Sildenafil Group
Time frame: Baseline and Week 12
Change in Arginase Activity From Baseline to Week 12 Among Sildenafil Group
Time frame: Baseline and Week 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Feb 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 23585527Morris 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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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ellis Neufeld, MD, PhD principal investigator
Boston Children's Hospital
Claudia Morris, MD study chair
Children's Hospital and Research Institute Oakland
Charles Quinn, MD principal investigator
University of Texas, Southwestern Medical Center at Dallas
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Sildenafil in people with Thalassemia and Hypertension, Pulmonary, run by Carelon Research at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Feb 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Feb 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Six-minute Walk Test (6MWT) Distance From Baseline to Week 12 Among Sildenafil Group (time frame: Baseline and Week 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00872170, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Feb 2014.