ClinicalTrials.gov
ClinicalTrials.gov Menu

Sildenafil Therapy for Pulmonary Hypertension and Sickle Cell Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00492531
Recruitment Status : Terminated (Subjects on drug were more likely to have severe pain crises requiring hospitalization.)
First Posted : June 27, 2007
Results First Posted : June 6, 2011
Last Update Posted : January 6, 2016
Sponsor:
Information provided by (Responsible Party):
Mark Gladwin, National Heart, Lung, and Blood Institute (NHLBI)

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Conditions Sickle Cell Disease
Pulmonary Hypertension
Interventions Drug: Sildenafil
Drug: Placebo
Enrollment 74

Recruitment Details Subjects with Sickle cell hemoglobinopathy were recruited from 10 centers(9 in United States and 1 in United Kingdom)
Pre-assignment Details  
Arm/Group Title Sildenafil Placebo
Hide Arm/Group Description Subjects received oral sildenafil 20 mg three times daily for six weeks, followed by 40 mg three times daily for four weeks, followed by 80 mg three times daily for six weeks (as tolerated). Subjects received matching oral dose of placebo 20 mg three times daily for six weeks, followed by 40 mg three times daily for four weeks, followed by 80 mg three times daily for six weeks (as tolerated).
Period Title: Overall Study
Started 37 37
Completed 15 [1] 14 [2]
Not Completed 22 23
Reason Not Completed
Withdrawn(More than one reason selected)             22             23
[1]
Of 15 subjects who completed study, 13 were enrolled in Open label.
[2]
Of 14 subjects who completed study, 13 were enrolled in Open label.
Arm/Group Title Sildenafil Placebo Total
Hide Arm/Group Description Subjects received oral sildenafil 20 mg three times daily for six weeks, followed by 40 mg three times daily for four weeks, followed by 80 mg three times daily for six weeks (as tolerated). Subjects received matching oral dose of placebo 20 mg three times daily for six weeks, followed by 40 mg three times daily for four weeks, followed by 80 mg three times daily for six weeks (as tolerated). Total of all reporting groups
Overall Number of Baseline Participants 37 37 74
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 37 participants 37 participants 74 participants
47  (13) 44  (14) 45  (13)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 37 participants 37 participants 74 participants
Female
23
  62.2%
23
  62.2%
46
  62.2%
Male
14
  37.8%
14
  37.8%
28
  37.8%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 37 participants 37 participants 74 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
0
   0.0%
Not Hispanic or Latino
32
  86.5%
37
 100.0%
69
  93.2%
Unknown or Not Reported
5
  13.5%
0
   0.0%
5
   6.8%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 37 participants 37 participants 74 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
36
  97.3%
37
 100.0%
73
  98.6%
White
0
   0.0%
0
   0.0%
0
   0.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
1
   2.7%
0
   0.0%
1
   1.4%
6 minute walk   [1] 
Mean (Standard Deviation)
Unit of measure:  Meters
Number Analyzed 37 participants 37 participants 74 participants
381  (75) 386  (75) 383  (75)
[1]
Measure Description: The distance walked in six minute was used to assess the exercise capacity of the patient at baseline.
Tricuspid regurgitant jet velocity (TRV)   [1] 
Mean (Standard Deviation)
Unit of measure:  M/s
Number Analyzed 37 participants 37 participants 74 participants
3.0  (0.5) 3.0  (0.3) 3.0  (0.3)
[1]
Measure Description: Tricuspid regurgitant jet velocity was measured by transthoracic Doppler Echocardiography.
1.Primary Outcome
Title Change in Exercise Capacity as Assessed by 6 Minute Walk.
Hide Description The primary outcome measure was change in exercise capacity assessed by 6 minute walk distance in meters from baseline to 16 weeks. Subjects without a week 16 assessment had their last observation carried forward.
Time Frame Baseline to week 16/Imputed last visit.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All efficacy and safety analyses were conducted on the intent-to-treat (ITT) population, defined as all randomized subjects, regardless of therapy received. Pre-defined imputation rules:A value of 0 meters was imputed for subjects who died during the MIT.Subjects without a week 16 assessment had their last observation carried forward (LOCF).
Arm/Group Title Sildenafil Placebo
Hide Arm/Group Description:
Subjects received oral sildenafil 20 mg three times daily for six weeks, followed by 40 mg three times daily for four weeks, followed by 80 mg three times daily for six weeks (as tolerated).
Subjects received matching oral dose of placebo 20 mg three times daily for six weeks, followed by 40 mg three times daily for four weeks, followed by 80 mg three times daily for six weeks (as tolerated).
Overall Number of Participants Analyzed 37 37
Mean (Standard Deviation)
Unit of Measure: meters
-16  (20) -7  (20)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sildenafil, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.70
Comments [Not Specified]
Method ANCOVA
Comments 6 minute walk was based on ANCOVA model with treatment as a fixed effect and 6 minute walk distance, TRV stratum and study site as covariate.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -9
Confidence Interval (2-Sided) 95%
-56 to 38
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline in Pulmonary Hypertension at Week 16 as Assessed by Tricuspid Regurgitant Jet Velocity
Time Frame 16 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Sildenafil Placebo
Hide Arm/Group Description:
Subjects received oral sildenafil 20 mg three times daily for six weeks, followed by 40 mg three times daily for four weeks, followed by 80 mg three times daily for six weeks (as tolerated).
Subjects received matching oral dose of placebo 20 mg three times daily for six weeks, followed by 40 mg three times daily for four weeks, followed by 80 mg three times daily for six weeks (as tolerated).
Overall Number of Participants Analyzed 37 37
Mean (Standard Deviation)
Unit of Measure: meters/second
Baseline 3.1  (0.5) 3.0  (0.3)
Week 6 3.2  (0.7) 2.9  (0.3)
Week 16 2.9  (0.5) 2.9  (0.3)
3.Secondary Outcome
Title Borg Dyspnea Score
Hide Description Borg dyspnea score was used to measure the level of severity of breathlessness perceived by the patient before and after 6 minute walk. The severity is measured on a 10 point scale with 0= nothing at all and 10=maximum severity of breathlessness.
Time Frame baseline to 16 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Sildenafil Placebo
Hide Arm/Group Description:
Subjects received oral sildenafil 20 mg three times daily for six weeks, followed by 40 mg three times daily for four weeks, followed by 80 mg three times daily for six weeks (as tolerated).
Subjects received matching oral dose of placebo 20 mg three times daily for six weeks, followed by 40 mg three times daily for four weeks, followed by 80 mg three times daily for six weeks (as tolerated).
Overall Number of Participants Analyzed 37 37
Mean (Standard Deviation)
Unit of Measure: Score on a scale
Baseline 2.5  (2.1) 2.1  (2.0)
Week 6 3.4  (2.3) 1.8  (1.3)
Week 10 2.7  (2.0) 2.7  (1.7)
Week 16 2.0  (1.6) 2.8  (2.4)
4.Secondary Outcome
Title Brain Natriuretic Peptide(BNP)Levels.
Hide Description [Not Specified]
Time Frame 16 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Sildenafil Placebo
Hide Arm/Group Description:
Subjects received oral sildenafil 20 mg three times daily for six weeks, followed by 40 mg three times daily for four weeks, followed by 80 mg three times daily for six weeks (as tolerated).
Subjects received matching oral dose of placebo 20 mg three times daily for six weeks, followed by 40 mg three times daily for four weeks, followed by 80 mg three times daily for six weeks (as tolerated).
Overall Number of Participants Analyzed 35 35
Mean (Standard Deviation)
Unit of Measure: pg/dl
Baseline 2.3  (0.6) 2.0  (0.6)
Week 6 2.4  (0.4) 2.0  (0.7)
Week 10 2.3  (0.5) 2.2  (0.6)
Week 16 2.5  (0.7) 2.3  (0.6)
Time Frame Safety assessments were conducted at baseline, weeks 6, 10 (excluding echocardiography), and 16.
Adverse Event Reporting Description Treatment group differences in AEs and SAEs were evaluated via Cochran-Mantel-Haenszel chi-square tests, controlling for TRV stratum. The study was stopped early due to the higher percentage of subjects experiencing an SAE in the sildenafil arm as compared to the placebo arm.
 
Arm/Group Title Sildenafil Placebo
Hide Arm/Group Description Subjects received oral sildenafil 20 mg three times daily for six weeks, followed by 40 mg three times daily for four weeks, followed by 80 mg three times daily for six weeks (as tolerated). Subjects received matching oral dose of placebo 20 mg three times daily for six weeks, followed by 40 mg three times daily for four weeks, followed by 80 mg three times daily for six weeks (as tolerated).
All-Cause Mortality
Sildenafil Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Sildenafil Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   17/37 (45.95%)   8/37 (21.62%) 
Blood and lymphatic system disorders     
Acute chest syndrome  1  1/37 (2.70%)  3/37 (8.11%) 
Anemia  1  2/37 (5.41%)  1/37 (2.70%) 
Cardiac disorders     
Atrial fibrillation  1  1/37 (2.70%)  0/37 (0.00%) 
Congestive Cardiac failure  1  1/37 (2.70%)  0/37 (0.00%) 
Congenital, familial and genetic disorders     
Sickle cell anemia with crisis  1  13/37 (35.14%)  5/37 (13.51%) 
Eye disorders     
Vitreous hemorrhage  1  1/37 (2.70%)  0/37 (0.00%) 
General disorders     
Pyrexia  1  1/37 (2.70%)  0/37 (0.00%) 
Infections and infestations     
Bronchitis  1  1/37 (2.70%)  0/37 (0.00%) 
Lower respiratory tract infection  1  1/37 (2.70%)  0/37 (0.00%) 
Injury, poisoning and procedural complications     
Traumatic brain injury  1  1/37 (2.70%)  0/37 (0.00%) 
Metabolism and nutrition disorders     
Hyperkalemia  1  0/37 (0.00%)  2/37 (5.41%) 
Psychiatric disorders     
Suicide attempt  1  1/37 (2.70%)  0/37 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Acute pulmonary edema  1  1/37 (2.70%)  0/37 (0.00%) 
Vascular disorders     
Hypertension  1  0/37 (0.00%)  1/37 (2.70%) 
Hypotension  1  1/37 (2.70%)  0/37 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (10.1)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Sildenafil Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   30   28 
Blood and lymphatic system disorders     
Blood and Lymphatic system disorders  1  4/37 (10.81%)  6/37 (16.22%) 
Congenital, familial and genetic disorders     
SCA with Crisis  1  18/37 (48.65%)  13/37 (35.14%) 
Eye disorders     
Eye disorders  1  5/37 (13.51%)  4/37 (10.81%) 
Blurred vision  1  5/37 (13.51%)  1/37 (2.70%) 
General disorders     
General Disorders and administration site conditions  1  6/37 (16.22%)  3/37 (8.11%) 
Infections and infestations     
Infections and infestations  1  5/37 (13.51%)  14/37 (37.84%) 
Musculoskeletal and connective tissue disorders     
Musculoskeletal and connective tissue disorders  1  5/37 (13.51%)  6/37 (16.22%) 
Nervous system disorders     
Headache  1  13/37 (35.14%)  4/37 (10.81%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (10.1)
As a result of early termination due to safety findings, the study was underpowered to assess the effects of sildenafil therapy on the predetermined efficacy endpoints.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Mark Gladwin
Organization: Professor of Medicine: Chief, Pulmonary, Allergy and Critical Care Medicine: Director, Hemostasis and Vascular Biology Research Institute; University of Pittsburgh School of Medicine
Phone: 412-692-2117
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Mark Gladwin, National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier: NCT00492531     History of Changes
Other Study ID Numbers: 070177
07-H-0177 ( Other Identifier: IRB Approval number , NHLBI )
First Submitted: June 26, 2007
First Posted: June 27, 2007
Results First Submitted: April 28, 2011
Results First Posted: June 6, 2011
Last Update Posted: January 6, 2016