Acute Effects of Inhaled Treprostinil in Fontan Patients

Congenital Heart Disease Clinical Trial

Official title:

A Randomized, Placebo-Controlled Pilot Study to Determine the Acute Effects of Inhaled Treprostinil on Exercise, Vascular Function, and Exercise Induced Liver Stiffness in Fontan Patients

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02769624
• Other study ID #: 2015-1491
• Status: Terminated
• Phase: Phase 2
• Start date: February 21, 2017
• Est. completion date: September 21, 2018

Study information

• Verified date: July 2020
• Source: Children's Hospital Medical Center, Cincinnati
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 15
• Est. completion date: September 21, 2018
• Est. primary completion date: September 21, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Patients age 18 years and older

2. Single ventricle patients status post Fontan procedure

Exclusion Criteria:

1. 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.

2. Evidence of Fontan pathway or intra cardiac obstruction as identified on prior clinically indicated imaging studies (echocardiography and MRI);

3. 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;

4. Presence of uncontrolled arrhythmias;

5. 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

6. Currently pregnant and/or breastfeeding

7. Patient unable to provide informed consent

8. BMI > 30 mg/m2

Related Conditions & MeSH terms

• Congenital Heart Disease
• Heart Diseases

Intervention

Drug:
• Treprostinil
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.
• Placebo
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.

Locations

Country	Name	City	State
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Children's Hospital Medical Center, Cincinnati

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Venous Pressure (mmHg) at Rest and Peak Exercise	Venous pressure was measured both at rest and during an incremental ramp exercise test. Comparison was made to evaluate if the treprostinil study medication had a different effect in venous pressure measurements during peak exercise versus placebo.	At rest and at peak incremental exercise
Secondary	Exercise Endurance Time (in Minutes)	A constant work rate exercise test will be performed to determine exercise endurance	Immediately following dose 3
Secondary	Peak Volume of Oxygen Consumption (VO2) (ml/kg/Min)	Measuring the difference in peak/maximal VO2 during incremental exercise testing to assess if the response during peak exercise is different when utilizing treprostinil versus a placebo.	Maximal exercise test (5-10 minutes)
Secondary	Minute Volume and Carbon Dioxide Volume Slope (VE/VCO2) During Incremental Exercise	Measuring the difference in peak/maximal VE/VCO2 during incremental exercise testing to assess if the response during peak exercise is different when utilizing treprostinil versus a placebo. The VE/VCO2 slope is used to show the relationship between minute ventilation and carbon dioxide production.	Maximal exercise test (5-10 minutes)
Secondary	VO2 (ml/kg/Min) at Anaerobic Threshold	Measuring the difference in VO2 at anaerobic threshold of an incremental exercise test to assess the variance in response with treprostinil versus placebo	Maximal exercise test (5-10 minutes)