NCT02741115CompletedPhase 3
Fontan Udenafil Exercise Longitudinal Assessment Trial (FUEL)
Mezzion Pharma Co. Ltd30 sites in 3 countries400 target enrollmentStarted: July 22, 2016Last updated:
Conditions
Interventions
Drugs
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Mezzion Pharma Co. Ltd
- Enrollment
- 400
- Locations
- 30
- Primary Endpoint
- Change in Maximal VO2 From Baseline to Week 26 Using Last Observation Carried Forward (LOCF)
Study Overview
Brief Summary
This study will evaluate the clinical efficacy and safety of udenafil, an orally administered, potent and selective inhibitor of PDE5, versus placebo for the treatment of adolescent subjects who have undergone the Fontan procedure.
Detailed Description
This study is a randomized, double-blinded, efficacy trial of the effects of udenafil vs. placebo on the background of standard therapy on maximal VO2 (ml/kg/min) from baseline to six months in adolescent survivors of the Fontan procedure. . The target sample size is 400 subjects (200 per group).
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 12 Years to 18 Years (Child, Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Males and females with Fontan physiology who are 12 to less than 19 years of age at enrollment.
- •Participant consent or parental/guardian consent and participant assent
- •Participant fluency in primary language of country in which study is being conducted
Exclusion Criteria
- •Weight < 40 kg
- •Height < 132 cm.
- •Hospitalization for acute decompensated heart failure within the last 12 months.
- •Current intravenous inotropic drugs.
- •Undergoing evaluation for heart transplantation or listed for transplantation.
- •Diagnosis of active protein losing enteropathy or plastic bronchitis within the last 3 years, or a history of liver cirrhosis.
- •Known Fontan baffle obstruction, branch pulmonary artery stenosis, or pulmonary vein stenosis resulting in a mean gradient of > 4 mmHg between the regions proximal and distal to the obstruction as measured by either catheterization or echocardiography, obtained prior to screening for the trial.
- •Single lung physiology with greater than 80% flow to one lung.
- •VO2 less than 50%
- •Severe ventricular dysfunction assessed qualitatively by clinical echocardiography within six months prior to enrollment.
- •Severe valvar regurgitation, ventricular outflow obstruction, or aortic arch obstruction assessed by clinical echocardiography within six months prior to enrollment.
- •Significant renal (serum creatinine > 2.0), hepatic (serum AST and/or ALT > 3 times upper limit of normal), gastrointestinal or biliary disorders that could impair absorption, metabolism or excretion of orally administered medications, based on laboratory assessment six weeks prior to screening for the trial.
- •Inability to complete exercise testing at baseline screening.
- •History of PDE-5 inhibitor use within 3 months before study onset.
- •History of any other medication for treatment of pulmonary hypertension within 3 months before study onset.
- •Known intolerance to oral udenafil.
- •Frequent use of medications or other substances that inhibit or induce CYP3A
- •Current use of alpha-blockers or nitrates.
- •Ongoing or planned participation in another research protocol that would either prevent successful completion of planned study testing or invalidate its results.
- •Noncardiac medical, psychiatric, and/or social disorder that would prevent successful completion of planned study testing or would invalidate its results.
- •Cardiac care, ongoing or planned, at a non-study center that would impede study completion.
- •For females: Pregnancy at the time of screening, pregnancy planned before study completion, or refusal to use an acceptable method of contraception for study duration if sexually active.
- •Unable to abstain or limit intake of grapefruit juice during the duration of the trial.
- •Refusal to provide written informed consent/assent.
- •In the opinion of the primary care physician, the subject is likely to be non-compliant with the study protocol.
Arms & Interventions
Drug
Experimental
Udenafil. One tablet twice daily for 26 weeks
Intervention: Udenafil (Drug)
Placebo
Experimental
Placebo. One tablet twice daily for 26 weeks
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Change in Maximal VO2 From Baseline to Week 26 Using Last Observation Carried Forward (LOCF)
Time Frame: Baseline to 26 Weeks
The change in exercise capacity (as measured by peak VO2 at maximum exercise effort) from baseline to 26 weeks
Secondary Outcomes
- Change in Myocardial Performance Index (MPI) From Baseline to Week 26(Week 26)
- Change in Log-transformed Reactive Hyperemia Index (InRH) From Baseline to Week 26(Week 26)
- Change in Serum Brain-type Natriuretic Peptide (BNP) From Baseline to Week 26.(Week 26)
- Change in VO2 at VAT(26 Weeks)
- Change in Work Rate at VAT From Baseline to Week 26 With LOCF(26 Weeks)
- Change in VE/VCO2 at VAT From Baseline to Week 26(26 Weeks)
- Change in Respiratory Rate at Maximal Exercise Effort From Baseline to Week 26 Using LOCF(Week 26)
- Change in Minute Oxygen Consumption at Maximal Exercise Effort From Baseline to Week 26(Week 26)
- Change in Work Rate at Maximal Exercise Effort Between Baseline and Week 26 Using LOCF(Week 26)
- Change in Pediatric Quality of Life (PedsQL) Generic Core Scales - Physical Functioning Subscale (Child Reported)(26 weeks)
- Change in Pediatric Quality of Life (PedsQL) Generic Core Scales - Physical Functioning Subscale (Parent Reported)(26 weeks)
- Change in Pediatric Quality of Life (PedsQL) Generic Core Scales - Psychosocial Health Subscale (Child Reported)(26 weeks)
- Change in Pediatric Quality of Life (PedsQL) Generic Core Scales - Psychosocial Health Subscale (Parent Reported)(26 weeks)
- Change in Pediatric Quality of Life (PedsQL) Inventory - Cardiac Module Scale - Treatment II Subscale (Child-reported)(26 weeks)
- Change in Pediatric Quality of Life (PedsQL) Inventory - Cardiac Module Scale - Perceived Physical Appearance Subscale(26 weeks)
- Change in Pediatric Quality of Life (PedsQL) Inventory - Cardiac Module Scale - Treatment Anxiety Subscale(26 weeks)
- Change in Pediatric Quality of Life (PedsQL) Inventory - Cardiac Module Scale - Cognitive Problems Subscale(26 weeks)
- Change in Pediatric Quality of Life (PedsQL) Inventory - Cardiac Module Scale - Communication Problems Subscale(26 weeks)
- Change in Pediatric Cardiac Quality of Life Inventory (PCQLI) Total Score-Ages 8 to 12 (Child Reported)(26 weeks)
- Change in Pediatric Cardiac Quality of Life Inventory (PCQLI) Total Score-Ages 8 to 12 (Parent Reported)(26 weeks)
- Change in Pediatric Cardiac Quality of Life Inventory (PCQLI) Total Score-Ages 13 to 18 (Child Reported)(26 weeks)
- Change in Pediatric Cardiac Quality of Life Inventory (PCQLI) Total Score-Ages 13 to 18 (Parent Reported)(26 weeks)
Investigators
Study Sites (30)
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