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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 (Responsible Party):
Mark Gladwin, National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier:
NCT00492531
First received: June 26, 2007
Last updated: December 7, 2015
Last verified: December 2015
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
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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Withdrawn(More than one reason selected)                22                23 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
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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).
Total Total of all reporting groups

Baseline Measures
   Sildenafil   Placebo   Total 
Overall Participants Analyzed 
[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]
     
Hispanic or Latino   0   0   0 
Not Hispanic or Latino   32   37   69 
Unknown or Not Reported   5   0   5 
Race (NIH/OMB) 
[Units: Participants]
     
American Indian or Alaska Native   0   0   0 
Asian   0   0   0 
Native Hawaiian or Other Pacific Islander   0   0   0 
Black or African American   36   37   73 
White   0   0   0 
More than one race   0   0   0 
Unknown or Not Reported   1   0   1 
6 minute walk [1] 
[Units: Meters]
Mean (Standard Deviation)
 381  (75)   386  (75)   383  (75) 
[1] The distance walked in six minute was used to assess the exercise capacity of the patient at baseline.
Tricuspid regurgitant jet velocity (TRV) [1] 
[Units: M/s]
Mean (Standard Deviation)
 3.0  (0.5)   3.0  (0.3)   3.0  (0.3) 
[1] Tricuspid regurgitant jet velocity was measured by transthoracic Doppler Echocardiography.


  Outcome Measures
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1.  Primary:   Change in Exercise Capacity as Assessed by 6 Minute Walk.   [ Time Frame: Baseline to week 16/Imputed last visit. ]
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Measure Type Primary
Measure Title Change in Exercise Capacity as Assessed by 6 Minute Walk.
Measure 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.  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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).

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).

Measured Values
   Sildenafil   Placebo 
Participants Analyzed 
[Units: Participants]
 37   37 
Change in Exercise Capacity as Assessed by 6 Minute Walk. 
[Units: Meters]
Mean (Standard Deviation)
 -16  (20)   -7  (20) 


Statistical Analysis 1 for Change in Exercise Capacity as Assessed by 6 Minute Walk.
Groups [1] All groups
Method [2] ANCOVA
P Value [3] 0.70
Mean Difference (Net) [4] -9
95% Confidence Interval -56 to 38
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  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.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



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

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

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


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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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.


  More Information