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Acute Effects of Inhaled Treprostinil in Fontan Patients

Primary Purpose

Congenital Heart Disease

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Treprostinil
Placebo
Sponsored by
Children's Hospital Medical Center, Cincinnati
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Congenital Heart Disease focused on measuring Congenital heart disease

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Cincinnati Children's Hospital Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Treprostinil

Placebo

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
Exercise Endurance Time (in Minutes)
A constant work rate exercise test will be performed to determine exercise endurance
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.
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.
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

Full Information

First Posted
May 10, 2016
Last Updated
July 13, 2020
Sponsor
Children's Hospital Medical Center, Cincinnati
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1. Study Identification

Unique Protocol Identification Number
NCT02769624
Brief Title
Acute Effects of Inhaled Treprostinil in Fontan Patients
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2020
Overall Recruitment Status
Terminated
Why Stopped
Study was stopped early due to inability to recruit additional participants
Study Start Date
February 21, 2017 (Actual)
Primary Completion Date
September 21, 2018 (Actual)
Study Completion Date
September 21, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Children's Hospital Medical Center, Cincinnati

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Congenital Heart Disease
Keywords
Congenital heart disease

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
15 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treprostinil
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Treprostinil
Other Intervention Name(s)
Tyvaso
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
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.
Primary Outcome Measure Information:
Title
Reduction in Liver Stiffness Through the Measurement of Shear Wave Ultrasound Elastography (m/s)
Description
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.
Time Frame
At rest and following dose 2
Secondary Outcome Measure Information:
Title
Venous Pressure (mmHg) at Rest and Peak Exercise
Description
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.
Time Frame
At rest and at peak incremental exercise
Title
Exercise Endurance Time (in Minutes)
Description
A constant work rate exercise test will be performed to determine exercise endurance
Time Frame
Immediately following dose 3
Title
Peak Volume of Oxygen Consumption (VO2) (ml/kg/Min)
Description
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.
Time Frame
Maximal exercise test (5-10 minutes)
Title
Minute Volume and Carbon Dioxide Volume Slope (VE/VCO2) During Incremental Exercise
Description
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.
Time Frame
Maximal exercise test (5-10 minutes)
Title
VO2 (ml/kg/Min) at Anaerobic Threshold
Description
Measuring the difference in VO2 at anaerobic threshold of an incremental exercise test to assess the variance in response with treprostinil versus placebo
Time Frame
Maximal exercise test (5-10 minutes)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients age 18 years and older Single ventricle patients status post Fontan procedure Exclusion Criteria: 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gruschen Veldtman, MBChB
Organizational Affiliation
Children's Hospital Medical Center, Cincinnati
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cincinnati Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States

12. IPD Sharing Statement

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Acute Effects of Inhaled Treprostinil in Fontan Patients

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