Acute Effects of Inhaled Treprostinil in Fontan Patients

NCT02769624 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 2015-1491
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

In this pilot study investigators propose to explore the effects of a locally delivered inhaled pulmonary vasodilator (inhaled treprostinil) on exercise performance, pulmonary blood flow, venous pressure response and vascular function in stable Fontan patients. Investigators will also assess the effects of resting and acute rises in exercise induced systemic venous pressure on liver stiffness and will also assess whether treprostinil will attenuate the acute stiffness increase that investigators expect to see. This will be a prospective, randomized, double-blinded placebo controlled, crossover trial. Following recruitment and informed consent, each participant will undergo three study visits, including baseline testing (visit 1), followed by two sets of exercise and vascular function tests (visit 2 and visit 3) at CCHMC. Twenty-six patients will be enrolled in this study.

Conditions

Congenital Heart Disease

Keywords

Congenital heart disease

Outcome Measures

Primary Outcomes (1)

• Reduction in Liver Stiffness Through the Measurement of Shear Wave Ultrasound Elastography (m/s)

  At rest and then following maximal exercise, shear wave ultrasound elastography will be performed to assess if the study medication shows an improvement in liver stiffness (reduction in m/s number) following maximal exercise versus at rest.

  At rest and following dose 2

Secondary Outcomes (5)

• Venous Pressure (mmHg) at Rest and Peak Exercise

  At rest and at peak incremental exercise

• Exercise Endurance Time (in Minutes)

  Immediately following dose 3

• Peak Volume of Oxygen Consumption (VO2) (ml/kg/Min)

  Maximal exercise test (5-10 minutes)

• Minute Volume and Carbon Dioxide Volume Slope (VE/VCO2) During Incremental Exercise

  Maximal exercise test (5-10 minutes)

• VO2 (ml/kg/Min) at Anaerobic Threshold

  Maximal exercise test (5-10 minutes)

Study Arms (2)

Treprostinil

EXPERIMENTAL

A dose of 18mcg (3 breaths) will be administered using the Tyvaso® (treprostinil) inhalation system. Tyvaso® (treprostinil) inhalation solution is supplied in 2.9 mL clear ampules packaged as four ampules in a foil pouch. Frequency and duration- 3 times over 1 study visit.

Drug: Treprostinil

Placebo

PLACEBO COMPARATOR

A dose of 3 breaths of placebo will be administered using the Tyvaso® (treprostinil) inhalation system. Placebo will be supplies in matching ampules to treprostinil. Volume will match that of treprostinil. Frequency and duration- 3 times over 1 study visit.

Drug: Placebo

Interventions

Treprostinil DRUG

A dose of 18mcg (3 breaths) will be administered 3 times: at baseline, 1.5 hrs. post baseline and then again 2 hrs later following maximal exercise testing.

Also known as: Tyvaso

Treprostinil

Placebo DRUG

3 breaths of placebo (via inhalation devices) will be administered 3 times: at baseline, 1.5 hrs. post baseline and then again 2 hrs later following maximal exercise testing.

Placebo

Eligibility Criteria

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

You may qualify if:

• Patients age 18 years and older
• Single ventricle patients status post Fontan procedure

You may not qualify if:

• Clinically unstable: these are patients who are experiencing new cardiovascular symptoms such as worsening shortness of breath, new onset arrhythmia, uncontrolled heart failure, or evidence of clinically significant cirrhosis or renal failure.
• Evidence of Fontan pathway or intra cardiac obstruction as identified on prior clinically indicated imaging studies (echocardiography and MRI);
• Evidence of left or right systemic ventricular systolic dysfunction with an Ejection fraction of \<40% on either echocardiogram or MRI from previously documented clinical data;
• Presence of uncontrolled arrhythmias;
• Unable to perform exercise testing for any reason or if deemed by the PI or designee that exercise testing would not be in the best interest of the participant
• Currently pregnant and/or breastfeeding
• Patient unable to provide informed consent
• BMI \> 30 mg/m2

Sponsors & Collaborators

• Children's Hospital Medical Center, Cincinnati: lead

Study Sites (1)

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

MeSH Terms

Conditions

Heart Defects, Congenital

Interventions

treprostinil

Condition Hierarchy (Ancestors)

Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Limitations and Caveats

This study had a small sample size and may have had selection bias towards well-functioning Fontan patients, who might benefit less from the use of pulmonary vasodilators. Additional physiological factors could have been assessed.

Results Point of Contact

• Title: Katy Fischesser
• Organization: Cincinnati Children's Hospital Medical Center

katy.fischesser@cchmc.org

513-803-5191

Study Officials

• Gruschen Veldtman, MBChB

  Children's Hospital Medical Center, Cincinnati

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 10, 2016
• First Posted: May 11, 2016
• Study Start: February 21, 2017
• Primary Completion: September 21, 2018
• Study Completion: September 21, 2018
• Last Updated: July 29, 2020
• Results First Posted: July 29, 2020

Record last verified: 2020-07

Locations

US (1)