Text Size

Sildenafil Therapy for Pulmonary Hypertension and Sickle Cell Disease

This study has been terminated.
(Subjects on drug were more likely to have severe pain crises requiring hospitalization.)
Sponsor:
Information provided by:
National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier:
NCT00492531
First received: June 26, 2007
Last updated: June 3, 2011
Last verified: June 2011
History of Changes
Results First Received: April 28, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Conditions: Sickle Cell Disease
Pulmonary Hypertension
Interventions: Drug: Sildenafil
Drug: Placebo

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Subjects with Sickle cell hemoglobinopathy were recruited from 10 centers(9 in United States and 1 in United Kingdom)

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Sildenafil 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).
Placebo 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).

Participant Flow:   Overall Study
    Sildenafil     Placebo  
STARTED     37     37  
COMPLETED     15 [1]   14 [2]
NOT COMPLETED     22     23  
Withdrawn(More than one reason selected)                 22                 23  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.



  Baseline Characteristics
  Hide Baseline Characteristics

Reporting Groups
  Description
Sildenafil 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).
Placebo 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 Total of all reporting groups

Baseline Measures
    Sildenafil     Placebo     Total  
Number of Participants  
[units: participants]
 		  37     37     74  
Age  
[units: years]
Mean ± Standard Deviation 		  47  ± 13     44  ± 14     45  ± 13  
Gender  
[units: participants]
 		     
Female     23     23     46  
Male     14     14     28  
Ethnicity (NIH/OMB)  
[units: Participants]
 		     
Not Hispanic or Latino     32     37     69  
Unknown or Not Reported     5     0     5  
Race (NIH/OMB)  
[units: participants]
 		     
Black or African American     36     37     73  
Unknown or Not Reported     1     0     1  
6 minute walk [1]
[units: Meters]
Mean ± Standard Deviation 		  381  ± 75     386  ± 75     383  ± 75  
Tricuspid regurgitant jet velocity (TRV) [2]
[units: m/s]
Mean ± Standard Deviation 		  3.0  ± 0.5     3.0  ± 0.3     3.0  ± 0.3  
[1] The distance walked in six minute was used to assess the exercise capacity of the patient at baseline.
[2] Tricuspid regurgitant jet velocity was measured by transthoracic Doppler Echocardiography.



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Change in Exercise Capacity as Assessed by 6 Minute Walk.   [ Time Frame: Baseline to week 16/Imputed last visit. ]
  Show Outcome Measure 1

2.  Secondary:   Change From Baseline in Pulmonary Hypertension at Week 16 as Assessed by Tricuspid Regurgitant Jet Velocity   [ Time Frame: 16 weeks ]
  Show Outcome Measure 2

3.  Secondary:   Borg Dyspnea Score   [ Time Frame: baseline to 16 weeks ]
  Show Outcome Measure 3

4.  Secondary:   Brain Natriuretic Peptide(BNP)Levels.   [ Time Frame: 16 weeks ]
  Show Outcome Measure 4


  Serious Adverse Events
  Show Serious Adverse Events


  Other Adverse Events
  Hide Other Adverse Events

Time Frame Safety assessments were conducted at baseline, weeks 6, 10 (excluding echocardiography), and 16.
Additional 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.

Frequency Threshold
Threshold above which other adverse events are reported   5%  

Reporting Groups
  Description
Sildenafil 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).
Placebo 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).

Other Adverse Events
    Sildenafil     Placebo  
Total, other (not including serious) adverse events      
# participants affected     30     28  
Blood and lymphatic system disorders      
Blood and Lymphatic system disorders † 1    
# participants affected / at risk     4/37 (10.81%)     6/37 (16.22%)  
Congenital, familial and genetic disorders      
SCA with Crisis † 1    
# participants affected / at risk     18/37 (48.65%)     13/37 (35.14%)  
Eye disorders      
Eye disorders † 1    
# participants affected / at risk     5/37 (13.51%)     4/37 (10.81%)  
Blurred vision † 1    
# participants affected / at risk     5/37 (13.51%)     1/37 (2.70%)  
General disorders      
General Disorders and administration site conditions † 1    
# participants affected / at risk     6/37 (16.22%)     3/37 (8.11%)  
Infections and infestations      
Infections and infestations † 1    
# participants affected / at risk     5/37 (13.51%)     14/37 (37.84%)  
Musculoskeletal and connective tissue disorders      
Musculoskeletal and connective tissue disorders † 1    
# participants affected / at risk     5/37 (13.51%)     6/37 (16.22%)  
Nervous system disorders      
Headache † 1    
# participants affected / at risk     13/37 (35.14%)     4/37 (10.81%)  
† Events were collected by systematic assessment
1 Term from vocabulary, MedDRA (10.1)



  More Information
  Hide More Information

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.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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.  


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
e-mail: gladwinmt@upmc.edu


Publications:

Publications automatically indexed to this study:


Responsible Party: Mark T. Gladwin, M.D.Professor of Medicine: Chief, Pulmonary, Allergy and Critical CRE Medicine: Director, Hemostasis and Vascular Biology Research Institute; University of Pittsburgh School of Medicine, Hemostasis and Vascular Biology Research Institute; University of Pittsburgh School of Medicine
ClinicalTrials.gov Identifier: NCT00492531     History of Changes
Other Study ID Numbers: 070177, 07-H-0177
Study First Received: June 26, 2007
Results First Received: April 28, 2011
Last Updated: June 3, 2011
Health Authority: United States: Federal Government
United States: Food and Drug Administration