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A 48-week Study of the Effect of Dual Therapy (Inhaled Treprostinil and Tadafafil) Versus Monotherapy (Tadalafil).

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ClinicalTrials.gov Identifier: NCT01305252
Recruitment Status : Completed
First Posted : February 28, 2011
Results First Posted : June 2, 2017
Last Update Posted : June 2, 2017
Sponsor:
Collaborator:
Northwestern University
Information provided by (Responsible Party):
Roham T. Zamanian, Stanford University

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Hypertension, Pulmonary
Interventions Drug: treprostinil inhalations
Drug: tadalafil
Enrollment 21
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Tadalafil Alone Tadalafil and Treprostinil Inhalations
Hide Arm/Group Description

tadalafil 40mg QD

tadalafil: tadalafil 20mg QD PO increasing to 40mg QD as tolerated

inhaled treprostinil: Treprostinil inhalation QID starting at 3 breaths per inhalation & gradually increasing to 9 breaths. Each breath provides approximately 6mcg of treprostinil.

tadalafil: tadalafil 20mg QD PO increasing to 40mg QD as tolerated

Period Title: Overall Study
Started 10 11
Completed 9 11
Not Completed 1 0
Arm/Group Title Tadalafil Alone Tadalafil and Treprostinil Inhalations Total
Hide Arm/Group Description

tadalafil 40mg QD

tadalafil: tadalafil 20mg QD PO increasing to 40mg QD as tolerated

inhaled treprostinil: Treprostinil inhalation QID starting at 3 breaths per inhalation & gradually increasing to 9 breaths. Each breath provides approximately 6mcg of treprostinil.

tadalafil: tadalafil 20mg QD PO increasing to 40mg QD as tolerated

Total of all reporting groups
Overall Number of Baseline Participants 10 11 21
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 11 participants 21 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
10
 100.0%
11
 100.0%
21
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 10 participants 11 participants 21 participants
51.6  (11.4) 52.1  (9.7) 51.9  (10.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 11 participants 21 participants
Female 7 9 16
Male 3 2 5
1.Primary Outcome
Title Change in Right Ventricular Ejection Fraction
Hide Description Effect of dual-upfront therapies versus mono-therapy on percent change of right ventricular function assesed by cardiac MRI (cMRI) at 24 weeks compared with the baseline.
Time Frame Basline and 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Tadalafil and Treprostinil Inhalations Tadalafil Alone
Hide Arm/Group Description:

Inhaled treprostinil: Treprostinil inhalation QID starting at 3 breaths per inhalation & gradually increasing to 9 breaths. Each breath provides approximately 6mcg of treprostinil.

Tadalafil: tadalafil 20mg QD PO increasing to 40mg QD as tolerated

Tadalafil 40mg QD

Tadalafil: tadalafil 20mg QD PO increasing to 40mg QD as tolerated

Overall Number of Participants Analyzed 11 10
Mean (Inter-Quartile Range)
Unit of Measure: percent change
7.45
(0.95 to 13.96)
2.8
(-1.49 to 7.09)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tadalafil and Treprostinil Inhalations
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.03
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Tadalafil Alone
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.17
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
2.Secondary Outcome
Title 6 Minute Walk Distance
Hide Description Change in 6MWD during 24 week period compared between Tada and Tada+iTre.
Time Frame Baseline and 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Tadalafil Alone Tadalafil and Treprostinil Inhalations
Hide Arm/Group Description:

Tadalafil 40mg QD

Tadalafil: tadalafil 20mg QD PO increasing to 40mg QD as tolerated

Inhaled treprostinil: Treprostinil inhalation QID starting at 3 breaths per inhalation & gradually increasing to 9 breaths. Each breath provides approximately 6mcg of treprostinil.

Tadalafil: tadalafil 20mg QD PO increasing to 40mg QD as tolerated

Overall Number of Participants Analyzed 10 11
Mean (Inter-Quartile Range)
Unit of Measure: meters
82.63
(23.40 to 141.86)
87.69
(6.98 to 168.41)
3.Secondary Outcome
Title N-terminal Pro B-type Natriuretic Peptide (NT-proBNP)
Hide Description Change from baseline in N-terminal Pro B-type Natriuretic Peptide (NT-proBNP)
Time Frame Baseline and 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Tadalafil and Treprostinil Inhalations Tadalafil Alone
Hide Arm/Group Description:

Inhaled treprostinil: Treprostinil inhalation QID starting at 3 breaths per inhalation & gradually increasing to 9 breaths. Each breath provides approximately 6mcg of treprostinil.

Tadalafil: tadalafil 20mg QD PO increasing to 40mg QD as tolerated

Tadalafil 40mg QD

Tadalafil: tadalafil 20mg QD PO increasing to 40mg QD as tolerated

Overall Number of Participants Analyzed 11 10
Mean (Standard Deviation)
Unit of Measure: pg/mL
1239  (1393) 988.4  (827.6)
4.Secondary Outcome
Title Change in NYHA/WHO Class
Hide Description

At 48 week,WHO/NYHA functional class was assessed for change in WHO/NYHA functional class.Change NYHA is measured as decrease or increase in NYHA class in the subjects compared with baseline.

NYHA /WHO functional class is described below:

NYHA functional class I:no symptoms and no limitation in ordinary physical activity NYHA functional class II:Mild symptoms (mild shortness of breath and/or angina) and slight limitation during ordinary activity NYHA functional class III:Marked limitation in activity due to symptoms, even during less-than-ordinary activity NYHA functional class IV:Severe limitations. Experiences symptoms even while at rest A higher functional class represent worse symptoms.

Time Frame Baseline and 48 week
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Tadalafil Alone Tadalafil and Treprostinil Inhalations
Hide Arm/Group Description:

Tadalafil 40mg QD

Tadalafil: tadalafil 20mg QD PO increasing to 40mg QD as tolerated

Inhaled treprostinil: Treprostinil inhalation QID starting at 3 breaths per inhalation & gradually increasing to 9 breaths. Each breath provides approximately 6mcg of treprostinil.

Tadalafil: tadalafil 20mg QD PO increasing to 40mg QD as tolerated

Overall Number of Participants Analyzed 10 11
Measure Type: Number
Unit of Measure: participants
6 11
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tadalafil Alone
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.03
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Tadalafil and Treprostinil Inhalations
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.33
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
5.Secondary Outcome
Title B-type Natriuretic Peptide (BNP)
Hide Description B-type Natriuretic peptide measures the percent change from baseline.
Time Frame Baseline and 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Tadalafil Alone Tadalafil and Treprostinil Inhalations
Hide Arm/Group Description:

tadalafil 40mg QD

tadalafil: tadalafil 20mg QD PO increasing to 40mg QD as tolerated

inhaled treprostinil: Treprostinil inhalation QID starting at 3 breaths per inhalation & gradually increasing to 9 breaths. Each breath provides approximately 6mcg of treprostinil.

tadalafil: tadalafil 20mg QD PO increasing to 40mg QD as tolerated

Overall Number of Participants Analyzed 10 11
Mean (Standard Deviation)
Unit of Measure: percent change
374  (133.8) 295.6  (133.2)
Time Frame initial 24 weeks
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Tadalafil Alone Tadalafil and Treprostinil Inhalations
Hide Arm/Group Description

tadalafil 40mg QD

tadalafil: tadalafil 20mg QD PO increasing to 40mg QD as tolerated

inhaled treprostinil: Treprostinil inhalation QID starting at 3 breaths per inhalation & gradually increasing to 9 breaths. Each breath provides approximately 6mcg of treprostinil.

tadalafil: tadalafil 20mg QD PO increasing to 40mg QD as tolerated

All-Cause Mortality
Tadalafil Alone Tadalafil and Treprostinil Inhalations
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Hide Serious Adverse Events
Tadalafil Alone Tadalafil and Treprostinil Inhalations
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/10 (10.00%)      0/11 (0.00%)    
Cardiac disorders     
Death  [1]  1/10 (10.00%)  1 0/11 (0.00%)  0
Indicates events were collected by systematic assessment
[1]
Death attributed to septic shock and ensuring renal failure.Not clinically deemed to be related to study medication.
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Tadalafil Alone Tadalafil and Treprostinil Inhalations
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   9/10 (90.00%)      8/11 (72.73%)    
Gastrointestinal disorders     
Diarrhea   1/10 (10.00%)  0/11 (0.00%) 
General disorders     
Nasal congestion/allergic Rhinitis   2/10 (20.00%)  5/11 (45.45%) 
Edema   0/10 (0.00%)  1/11 (9.09%) 
Infections and infestations     
Upper respiratory tract infection   2/10 (20.00%)  3/11 (27.27%) 
Dental infection   3/10 (30.00%)  0/11 (0.00%) 
Musculoskeletal and connective tissue disorders     
musculoskeletal pain   1/10 (10.00%)  3/11 (27.27%) 
Respiratory, thoracic and mediastinal disorders     
Asthma   1/10 (10.00%)  0/11 (0.00%) 
Skin and subcutaneous tissue disorders     
Dermatitis   0/10 (0.00%)  1/11 (9.09%) 
Indicates events were collected by systematic assessment
Limitations: small,2 center study,Placebo Un-blinded,Limited event rates/Time to clinical worsening and harmonization of measures.
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
Layout table for Results Point of Contact information
Name/Title: Roham Zamanian, MD, FCCP
Organization: Stanford University School of Medicine
Phone: 650- 725-5495
EMail: zamanian@stanford.edu
Layout table for additonal information
Responsible Party: Roham T. Zamanian, Stanford University
ClinicalTrials.gov Identifier: NCT01305252    
Other Study ID Numbers: SU-07152010-6565
IRB protocol # 18305
First Submitted: November 2, 2010
First Posted: February 28, 2011
Results First Submitted: November 21, 2016
Results First Posted: June 2, 2017
Last Update Posted: June 2, 2017