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

NCT01305252 | Completed Phase 4 Results DMC

• 2 other identifiers: SU-07152010-6565IRB protocol # 18305
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 2

Brief Summary

The Study Hypothesis: Aggressive, upfront, dual therapy for treatment-naïve NYHA I/II/III PAH is superior to a traditional "step-up" approach. The study will evaluate:

1. 1.Impact of dual, upfront, therapy on cardiovascular parameters in PAH as gauged by cardiac magnetic resonance imaging (cMRI) at 24 weeks and event free survival at outcome at 48 weeks.
2. 2.Value of novel biomarkers (NT-pro BNP, Mts1/S100A4, and insulin resistance) and cutting-edge imaging technologies (cardiac MRI) as newer endpoints for clinical trials in PAH.
3. 3.Utility of longer clinical trial design with the use of combined clinical events as time to clinical worsening surrogate

Conditions

Hypertension, Pulmonary

Outcome Measures

Primary Outcomes (1)

• Change in Right Ventricular Ejection Fraction

  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.

  Basline and 24 weeks

Secondary Outcomes (4)

• 6 Minute Walk Distance

  Baseline and 24 weeks

• N-terminal Pro B-type Natriuretic Peptide (NT-proBNP)

  Baseline and 24 weeks

• Change in NYHA/WHO Class

  Baseline and 48 week

• B-type Natriuretic Peptide (BNP)

  Baseline and 24 weeks

Study Arms (2)

tadalafil alone

ACTIVE COMPARATOR

tadalafil 40mg QD(Tadalafil 20 mg QD PO increasing to 40 mg QD as tolerated).

Drug: tadalafil

tadalafil and treprostinil inhalations

ACTIVE COMPARATOR

Treprostinil inhalation QID starting at 3 breaths per inhalation \& gradually increasing to 9 breaths.Each breath provides approximately 6 mcg of treprostinil.Tadalafil 20 mg QD PO increasing to 40 mg QD as tolerated.

Drug: treprostinil inhalations; Drug: tadalafil

Interventions

treprostinil inhalations DRUG

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

Also known as: Tyvaso

tadalafil and treprostinil inhalations

tadalafil DRUG

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

Also known as: Adcirca

tadalafil alone; tadalafil and treprostinil inhalations

Eligibility Criteria

• Age: 18 Years - 69 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 and \< 75 years at baseline visit.
• Diagnosis of Idiopathic PAH, Heritable PAH (including Hereditary Hemorrhagic Telangiectasia), Associated PAH (including collagen vascular disorders, drug+toxin exposure, repaired congenital heart disease repaired \> 5 years, portopulmonary disease, and human immunodeficiency virus (HIV) infection not on protease inhibitor).
• PAH treatment naïve including any prostacycline, endothelin receptor antagonist, or phosphodiesterase inhibitors within 12 months prior to enrollment.
• Previous Right Heart Catheterization that documented:
• Mean PAP; 25 mmHg.
• Pulmonary capillary wedge pressure \< 15 mmHg.
• Pulmonary Vascular Resistance; 3.0 Wood units or 240 dynes/sec/cm5 5.6MW distances; 150 m and \< 450 meters.
• \. WHO functional class II or III as judged by principal investigators.

You may not qualify if:

• Group II - V pulmonary hypertension.
• PAH with unrepaired congenital heart defect.
• Current or prior PAH treatments within the last 6-12 months including experimental PAH therapies (including but not limited to tyrosine kinase inhibitors, rho-kinase inhibitors, phosphodiesterase inhibitors, prostacycline, or cGMP modulators).
• TLC \< 60% predicted; if TLC b/w 60 and 70% predicted, high resolution computed tomography must be available to exclude significant interstitial lung disease.
• FEV1 / FVC \< 70% predicted and FEV1 \< 60% predicted
• Significant left-sided heart disease (based on pre-trial Echocardiogram):
• Significant aortic or mitral valve disease
• Diastolic dysfunction ; Grade II C.LV systolic function \< 45%
• d. Pericardial constriction e. Restrictive cardiomyopathy f. Significant coronary disease with demonstrable ischemia
• Chronic renal insufficiency defined as an estimated creatinine clearance \< 30 ml/min (by MDRD equation)
• Current atrial arrhythmias
• Uncontrolled systemic hypertension: SBP \> 160 mm or DBP \> 100mm
• Severe hypotension: SBP \< 80 mmHg.
• Pregnant or breast-feeding
• Psychiatric, addictive, or other disorder that compromises patient's ability to provide informed consent, follow study protocol, and adhere to treatment instructions

Sponsors & Collaborators

• Stanford University: lead
• Northwestern University: collaborator

Study Sites (2)

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

Northwestern University

Chicago, Illinois, 60208, United States

Location

MeSH Terms

Conditions

Hypertension, Pulmonary

Interventions

treprostinil; Tadalafil

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Carbolines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indole Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring

Limitations and Caveats

Limitations: small,2 center study,Placebo Un-blinded,Limited event rates/Time to clinical worsening and harmonization of measures.

Results Point of Contact

• Title: Roham Zamanian, MD, FCCP
• Organization: Stanford University School of Medicine

zamanian@stanford.edu

650- 725-5495

Study Officials

• Roham T. Zamanian

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principle Investigator

Study Record Dates

• First Submitted: November 2, 2010
• First Posted: February 28, 2011
• Study Start: July 1, 2010
• Primary Completion: September 1, 2014
• Study Completion: September 1, 2014
• Last Updated: June 2, 2017
• Results First Posted: June 2, 2017

Record last verified: 2017-04

Locations

US (2)