Prednisone for Heart Failure Patients With Hyperuricemia (PUSH-PATH-2)

Prednisone in Uric Acid Lowering in Symptomatic Heart Failure PATients With Hyperuricemia (PUSH-PATH Study 2)

Hyperuricemia is a very common finding in patients with heart failure. It is usually related to diuretic use and deteriorated renal function. The recently evidence showed that prednisone and allopurinol may have similar effect on uric acid (UA) lowering in symptomatic heart failure patients with hyperuricemia, but prednisone may be superior over allopurinol in renal function improvement. Thus the investigators design this randomized head to head study to test their hypothesis that prednisone is superior over allopurinol in renal function improvement despite their similar effect on UA lowering in heart failure patients with hyperuricemia.

Study Overview

• Status: Completed
• Conditions: Heart Failure, Hyperuricemia
• Intervention / Treatment: Drug: Prednisone; Drug: Allopurinol

Detailed Description

Hyperuricemia in heart failure (HF) is linked to renal impairment, hemodynamic compromise, and inflammation. Hyperuricemic HF patients are characterized by worsening of renal function and fragile volume state, both of which restrict the use of non-steroidal anti-inflammatory drugs (NSAIDs) when treating concurrent inflammatory diseases. Recent small studies suggest that steroidal anti-inflammatory drug, prednisone, may have renal protective, UA lowering, and potentiating diuretic effects in hyperuricemic HF patients. However, general acceptance of prednisone as a treatment option for anti-inflammation therapy in patients with hyperuricemic HF requires more safety data. We therefore designed a randomized study to compare the safety and renal protective effects of short-term use of prednisone with allopurinol, a widely used xanthine oxidase inhibitor with a well-established safety profile in HF, in hyperuricemic HF patients.

• Study Type: Interventional
• Enrollment (Actual): 205
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• China
  • Hebei
    • Shijiazhuang, Hebei, China, 050031

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• chronic congestive heart failure
• 18-80 years old
• NYHA Class II-IV
• Serum uric acid > 7mg/dl
• left ventricular ejection fraction ≤ 45%

Exclusion Criteria:

• Acute gouty arthritis;
• Any condition (other than heart failure) that could limit the use of prednisone or xanthine oxidase inhibitors;
• Acute decompensated heart failure;
• Any concurrent disease that likely limits life expectancy;
• Active myocarditis, or an hypertrophic obstructive or restrictive cardiomyopathy;
• Myocardial infarction, stroke, unstable angina, or cardiac surgery within the previous 3 months;
• Indication for hemodialysis
• Creatinine> 3.0 mg per deciliter at admission to the hospital
• Uncontrolled systolic blood pressure > 140 mmHg
• Known bilateral renal artery stenosis
• Complex congenital heart disease
• Any signs of infections
• Enrollment in another clinical trial involving medical or device-based interventions

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Prednisone; Prednisone will be given 30mg/day for 2 weeks and then tapered off.	Drug: Prednisone
ACTIVE_COMPARATOR: Allopurinol; Allopurinol will be given 100 mg/day initially, and then titrated to 200 mg/day.	Drug: Allopurinol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in serum creatinine levels	Change from baseline in serum creatinine levels at the end of study, i.e. 2 weeks	2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in uric acid levels	Change from baseline in uric acid levels at the end of study, i.e. 2 weeks	2 weeks
Change from baseline in Cystatin C	Change from baseline in cystatin c at the end of study, i.e. 2 weeks.	2 weeks
the levels of tumor necrosis factor (TNF) alfa,IL-6 in the circulation, high-sensitivity C-reactive Protein (hs-CRP)	Change of plasma TNF-alfa, IL-6, and hs-CRP levels at the end of study, i.e. 2 weeks (expressed as percentage of baseline)	2 weeks
The levels of angiotensin II and aldosterone in the circulation.	Change of plasma angiotensin II and aldosterone at end of week-1 (i.e. on day 7) and at the end of week-2 (i.e. on day 14), the values were expressed as percentage of baseline)	2 weeks
Daily urine output	24-hour urine output at week-1 (i.e. on day 7) and at week-2 (i.e. on day 14)	2 weeks
New York Heart Association (NYHA) functional class	Change of NHHA functional class at the end of study	2 weeks
24h urinary sodium excretion	24-hour urinary sodium excretion at week-1 (i.e. on day 7) and at week-2 (i.e. on day 14)	2 weeks

Collaborators and Investigators

• Sponsor: Hebei Medical University

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 1, 2013
• Primary Completion (ACTUAL): February 1, 2018
• Study Completion (ACTUAL): August 31, 2018

Study Registration Dates

• First Submitted: April 30, 2014
• First Submitted That Met QC Criteria: April 30, 2014
• First Posted (ESTIMATE): May 2, 2014

Study Record Updates

• Last Update Posted (ACTUAL): October 16, 2018
• Last Update Submitted That Met QC Criteria: October 12, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Heart Failure; Hyperuricemia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antimetabolites; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protective Agents; Antioxidants; Free Radical Scavengers; Gout Suppressants; Prednisone; Allopurinol
• Other Study ID Numbers: PUSH-PATH 2