A Phase 2 interventional study of Treprostinil and Placebo in Congenital Heart Disease, sponsored by Children's Hospital Medical Center, Cincinnati. Terminated at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2020-07-29.
Sponsored by Children's Hospital Medical Center, Cincinnati · Phase 2, Interventional, and Supportive care
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.
3,639 studies on the registry are indexed under Heart Diseases; 461 are open to participants now.
This study's enrollment of 15 is below the median of 100 across 1,778 interventional studies indexed under Heart Diseases.
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Exclusion Criteria:
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
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
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
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.
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.
Time frame: At rest and following dose 2
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.
Time frame: At rest and at peak incremental exercise
Exercise Endurance Time (in Minutes)
A constant work rate exercise test will be performed to determine exercise endurance
Time frame: Immediately following dose 3
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.
Time frame: Maximal exercise test (5-10 minutes)
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.
Time frame: Maximal exercise test (5-10 minutes)
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
Time frame: Maximal exercise test (5-10 minutes)
This was a randomized, placebo-controlled, double-blind, crossover trial conducted at one center. Healthy Fontan patients were recruited from within the medical center's Fontan management program for participation in this trial. Each patient completed three study visits over the course of six weeks.
| Milestone | Treprostinil, Then Placebo | Placebo, Then Treprostinil |
|---|---|---|
| Started | 7 | 8 |
| Completed | 7 | 7 |
| Not completed | 0 | 1 |
| Withdrew: Lost to follow-up | 0 | 1 |
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.
| m/s | Treprostinil | Placebo |
|---|---|---|
| Rest | 2.39 ± 0.67 | 2.38 ± 0.71 |
| Following maximal exercise | 2.79 ± 0.54 | 2.89 ± 0.51 |
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.
| mmHg | Treprostinil | Placebo |
|---|---|---|
| Rest | 12.8 ± 3.08 | 12.1 ± 2.43 |
| Peak Incremental Exercise | 22.8 ± 6.16 | 22.6 ± 8.04 |
A constant work rate exercise test will be performed to determine exercise endurance
| Minutes | Treprostinil | Placebo |
|---|---|---|
| Exercise Endurance Time (in Minutes) | 5.19 ± 0.89 | 5.82 ± 1.23 |
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.
| ml/kg/min | Treprostinil | Placebo |
|---|---|---|
| Peak Volume of Oxygen Consumption (VO2) (ml/kg/Min) | 23.4 ± 6.67 | 24.6 ± 9.04 |
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.
| unitless | Treprostinil | Placebo |
|---|---|---|
| Minute Volume and Carbon Dioxide Volume Slope (VE/VCO2) During Incremental Exercise | 26.8 ± 4.95 | 26.1 ± 6.35 |
Measuring the difference in VO2 at anaerobic threshold of an incremental exercise test to assess the variance in response with treprostinil versus placebo
| ml/kg/min | Treprostinil | Placebo |
|---|---|---|
| VO2 (ml/kg/Min) at Anaerobic Threshold | 17.3 ± 3.63 | 18.1 ± 5.36 |
Collected over Adverse events were assessed and recorded following signing of informed consent through two weeks following the last study visit (period ranging from 6-9 weeks).. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Treprostinil | 0/14 (0%) | 0/14 (0%) | 11/14 (78.6%) |
| Placebo | 0/15 (0%) | 0/15 (0%) | 4/15 (26.7%) |
| Event | Treprostinil | Placebo |
|---|---|---|
| CoughRespiratory, thoracic and mediastinal disorders | 10/14 | 0/15 |
| NauseaGastrointestinal disorders | 3/14 | 0/15 |
| Sore ThroatRespiratory, thoracic and mediastinal disorders | 3/14 | 0/15 |
| Chest TightnessRespiratory, thoracic and mediastinal disorders | 2/14 | 0/15 |
| DizzinessEar and labyrinth disorders | 1/14 | 2/15 |
| Increase in Liver Lab ValuesHepatobiliary disorders | 1/14 | 0/15 |
| HeadacheMusculoskeletal and connective tissue disorders | 1/14 | 1/15 |
| WeaknessGeneral disorders | 1/14 | 1/15 |
| Lowered blood pressureCardiac disorders | 1/14 | 1/15 |
| Abnormal ECG RhythmCardiac disorders | 0/14 | 1/15 |
Fifteen participants began the study, however, only 14 completed both the study medication and placebo components of the trial.
| Age, Categorical(Participants) | Treprostinil Crossover With Placebo |
|---|---|
| <=18 years | 0 |
| Between 18 and 65 years | 14 |
| >=65 years | 0 |
| Sex: Female, Male(Participants) | Treprostinil Crossover With Placebo |
|---|---|
| Female | 9 |
| Male | 5 |
| Race and Ethnicity Not Collected(Participants) | Treprostinil Crossover With Placebo |
|---|
| Region of Enrollment(participants) | Treprostinil Crossover With Placebo |
|---|---|
| United States | 14 |
| Cardiac Anatomy(Participants) | Treprostinil Crossover With Placebo |
|---|---|
| Tricuspid Atresia | 4 |
| Double Inlet Left Ventricle | 2 |
| Pulmonary Atresia | 2 |
| Hypoplastic Left Heart Syndrome | 6 |
| Fontan Type(Participants) | Treprostinil Crossover With Placebo |
|---|---|
| Atrio-pulmonary Fontan | 2 |
| Lateral Tunnel | 9 |
| Extracardiac Conduit | 3 |
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Children's Hospital Medical Center, Cincinnati