Opportunities for Collaboration in Trials
These trials are occurring in various NECCA sites; please contact the PI if you have interest or patients to share:
Fontan Udenafil Exercise Longitudinal Assessment Trial (FUEL)
As you may know, the Pediatric Heart Network has initiated a study examining the effect of udenafil (a b.i.d. medication similar to sildenafil) on the exercise function of Fontan patients. The study is a randomized, double blind, placebo controlled trial. Patients will be treated with udenafil or placebo for 6 months. Patients between 12 and 18 yrs of age are eligible to participate. All patients will have an exercise test, echo and vascular function test (Endopat) and then will be randomized to the udenafil or placebo arm. These tests will be repeated at the end of the 6 months of treatment. Two brief visits during the 6 months of treatment are also required. Patients will receive $300 compensation for participating in the study. Parking (and for out-of-town patients, hotel accommodations) will also be covered.
This is an important study examining the value of this type of pulmonary vasodilator therapy in Fontan patients. The study hopes to recruit 400 patients. 24 centers across the US are participating in the study. Boston Children’s Hospital is the New England center, and the PHN is hoping that we recruit 40-60 subjects. That is a pretty ambitious target, and any assistance from the NECCA community would be greatly appreciated. Please call Jonathan Rhodes (617-355-8165) if you have any questions or comments.
Neurocognitive Function of Adolescents and Young Adults with Repaired Complex Congenital Heart Disease after Recent Cardiac Re-Interventions Comparison Study
The University of Michigan has initiated a study aiming to compare the neurological differences between patients undergoing surgical versus transcatheter-based pulmonary valve replacements. Patients between 13 and 30 years old who have congenital heart disease that required an open heart operation during infancy (before 1 year of age) and have a planned surgical or catheter-based PVR are eligible to participate. Participants will fill out a depression screen survey, a quality of life survey, and a neurocognitive survey before their planned procedure. Three months post-procedure, the patients will fill out the quality of life survey and neurocognitive again by mail. One year post-procedure, the patients will fill out the quality of life and neurocognitive surveys again by mail, the depression screen survey by phone, and will undergo a clinical assessment, which can be completed at their local cardiologist’s office. Patients will receive a total of $50 compensation for participating in the study: one $25 gift card to Au Bon Pain at enrollment, and one check for $25 at study completion.
This study hopes to recruit 120 patients. 6 centers across the United States participate in the study. Boston Children’s Hospital hopes to recruit 20 patients – 10 for the surgical cohort and 10 for the catheter-based cohort. Any assistance from the NECCA community would be greatly appreciated in reaching this target. Please call Lisa Bergersen (617-355-8228) if you have any questions or comments.
Evaluation of the safety and efficacy of Entresto® in children (1 month to <18 years) with heart failure due to systemic left ventricular Systolic dysfunction (PANORAMA_HF Study)
Entresto® (LCZ696) is a first-in-class combination of an angiotensin receptor blocker (valsartan) and a neprilysin inhibitor (sacubitril) designed for treatment for chronic heart failure. Neprilysin inhibition slows the breakdown of small endogenous vasoactive peptides which potentiates their activity when secreted by the heart in response to cardiac stress and increases intravascular volume. PARADIGM-HF, a recent randomized controlled study in adults with heart failure and reduced ejection fraction, demonstrated that Entresto® was superior to enalapril in delaying time to first occurrence of cardiovascular death or hospitalization. Importantly, the time to cardiovascular death was longer in patients receiving Entresto®.1
The PANORAMA-HF Study will be performed in children between the ages of 1 month and 18 years with two ventricle physiology and heart failure due to reduced ejection fraction of the systemic left ventricle (LVEF ≤ 40%). The study consists of two parts; Part 1 is a dose escalation study to evaluate the pharmacokinetics and pharmacodynamics of Entresto® and Part 2 is a 52-week randomized, double blind study that will evaluate the efficacy, safety and tolerability of LCZ696 compared to enalapril in addition to conventional HF treatment in pediatric patients with heart failure. Enrolled participants will receive either enalapril or LCZ696 but will be blinded to their treatment. Participants will have clinic visits every three months with telephone visits in between.
Part 1: Recruitment is now open to subjects aged 1 to 6 years old. Recruitment for 1 month to 1 year olds will follow. This part involves administration of Entresto® at dose of 0.8 mg/kg and/or 3.1 mg/kg. Subjects will have an IV placed for pharmacokinetic blood draws over a 10 hour post-dose interval. Testing will also include a physical exam, an EKG and an ECHO. Patients will continue to be followed with clinic visits every three months until Part 2 starts for their age group with telephone visits in between. Subjects will receive reimbursement for travel expenses ($190 per visit). Telephone visits pay $50.
Part 2: Recruitment is expected to start for 6 to 18 year old patients once the data from Part 1 is reviewed by the FDA. This may occur in the summer of 2017. Each participant will receive one active drug and one placebo dispensed by the research pharmacy. Participants will have clinic visits every three months with telephone visits in between. Assessments performed at each research visit include physical examination, heart failure classification, quality of life questionnaires, adverse events screen, and laboratory studies. Subjects will receive reimbursement for travel expenses ($190 per visit). Telephone visits pay $50.
The study is sponsored by Novartis Pharmaceuticals Corporation and is enrolling subjects at Boston Children’s Hospital. Please contact the study PI, Dr. Kevin Daly at 617-355-6329 or firstname.lastname@example.org, for further information.
1 McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, Rouleau JL, Shi VC, Solomon SD, Swedberg K and Zile MR. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371:993-1004.