Clinical trial NCT02769611: Ruboxistaurin in New York Heart Failure Classification III-IV Patients
Official title: A Prospective Phase I/II Dose Escalation Pilot Analysis of Ruboxistaurin (LY333531) for Safety in New York Heart Failure Classification III-IV Patients, As Well As For Efficacy in Acutely Augmenting Cardiac Function.
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: Heart Failure
Lead sponsor: University of Tennessee
Sponsor class: OTHER
Collaborators: name: The Christ Hospital
First posted: 2016-05-11
Enrollment: 0
Sex: ALL
Minimum age (years): 30
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study evaluates the effect of ruboxistaurin for its safety, tolerability, and effectiveness in treating adult patients with heart failure. Patients will receive 1 dose of oral ruboxistaurin.

Detailed description: Ruboxistaurin is a drug initially developed for treatment of diabetic peripheral retinopathy. The proposed indication for ruboxistaurin in this study is the treatment of adult patients with New York Heart Failure Association (NYHA) Class III-IV heart failure. Ruboxistaurin is a protein kinase c-alpha (PKC-alpha) inhibitor and thus will produce an inotropic effect in the heart which holds the potential to improve cardiac function.

Eligibility criteria: Inclusion Criteria:

1. Male or female, 30-75 years of age, inclusive
2. NYHA Class III-IV heart failure (HF) confirmed left ventricular systolic dysfunction with left ventricular ejection fraction (LVEF) \<40% as assessed by noninvasive imaging studies such as echocardiography or cardiac MRI within the last 6 months admitted with decompensated heart failure and almost ready for clinical discharge
3. Patient must have had adequate therapy for acute decompensated HF (heart failure) episode prior to enrollment

Exclusion Criteria:

1. Patients with acute coronary syndrome
2. Resynchronization therapy initiated less than 90 days prior to enrollment
3. (LVAD) left ventricular assist device or heart transplantation expected within the next 3 months
4. Patients on hemodialysis or end stage renal disease (ESRD)
5. Patients with serum albumin less than 3 g/dL or evidence of liver cirrhosis
6. Patients with uncontrolled arterial hypertension (systolic blood pressure \> 180 or diastolic blood pressure \>110)
7. Patients with severe valvular heart disease
8. Patients with acute myocarditis
9. Patients with serum creatinine \>3.0 mg/dl or BUN \>70 mg/dL
10. Patients with hemodynamic instability or significant active arrhythmias
11. Patients currently on intravenous inotropic therapy or those that have received inotropic therapy within the last 24 hours prior to study enrollment
12. Patients currently on CYP3A inhibitors, or patients that have taken CYP3A inhibitors within 3 months prior to enrollment
13. Patients with ongoing ischemia
14. Patients who have had a myocardial infarction within 30 days prior to study enrollment
15. Patients who are pregnant, nursing, or planning to become pregnant during the study period

Primary outcomes:
measure: Percent of patients with a new onset, clinically significant arrhythmia or conduction system disease,
timeFrame: 48 hours
measure: Percent of patients with significant prolongation in the corrected QT (QTc) interval
timeFrame: 24 hours
measure: Percent of patients with significant increase in liver function tests
timeFrame: 12 hours
measure: Percent of patients with a significant increase in serum creatinine not explained by diuretic use.
timeFrame: 12 hours
measure: Percent of patient with a significant increase in serum creatine phosphokinase (CPK) levels
timeFrame: 12 hours
Secondary outcomes:
measure: Percent of patients experiencing at least one adverse event
timeFrame: 30 days
measure: Change in cardiac contractility as assessed by echocardiography.
timeFrame: 4 hours
measure: Change in self-reported well-being, fatigue and dyspnea
timeFrame: 8 hours, 24 hours
Other outcomes:
Locations:
city: Cincinnati
country: United States
facility: The Lindner Center for Research and Education at The Christ Hospital
state: Ohio
Study officials:
affiliation: Children's Hospital Medical Center, Cincinnati
name: John L Jefferies, MD
role: PRINCIPAL_INVESTIGATOR
References: