Phosphodiesterase Type 5 Inhibition With Tadalafil Changes Outcomes in Heart Failure: Extent of Renal Damage
Information source: Massachusetts General Hospital
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Heart Failure; Pulmonary Hypertension
Intervention: Tadalafil (Drug); Placebo (Drug)
Phase: Phase 3
Status: Withdrawn
Sponsored by: Massachusetts General Hospital Official(s) and/or principal investigator(s): Ravi I Thadhani, MD, MPH, Principal Investigator, Affiliation: Massachusetts General Hospital Ishir Bhan, MD, MPH, Principal Investigator, Affiliation: Massachusetts General Hospital
Summary
PITCH-ER is an ancillary study of PITCH-HF (NCT01910389). The goal of the PITCH-ER ancillary
study is to evaluate the rate of decline in renal function and frequency of development of
acute kidney injury (AKI) in patients enrolled in PITCH-HF (who have heart failure and
pulmonary hypertension) treated with chronic tadalafil treatment compared to placebo.
Clinical Details
Official title: Phosphodiesterase Type 5 Inhibition With Tadalafil Changes Outcomes in Heart Failure: Extent of Renal Damage (PITCH-ER)
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention
Primary outcome: Change in renal functionIncidence of acute kidney injury (AKI) events (clinical and subclinical)
Secondary outcome: Changes in renal function stratified by diabetes/no diabetesIncidence of AKI events stratified by diabetes/no diabetes
Detailed description:
The National Heart, Lung, and Blood Institute (NHLBI)-funded parent study (PITCH-HF) is the
first well-controlled, randomized, large-scale trial studying the effect of tadalafil, an
FDA-approved selective phosphodiesterase type 5 inhibitor (PDE5i), on cardiovascular and
heart failure-related deaths and hospitalizations in patients with heart failure and
secondary pulmonary hypertension.
Both chronic kidney disease (CKD), as reflected by albuminuria and reduced estimated
glomerular filtration rate (eGFR) and acute kidney injury (AKI) significantly contribute to
morbidity and mortality in the population of patients who will be enrolled in PITCH-HF.
Therapies that alter the course of renal disease in patients with heart failure are lacking.
The biology of treatment with PDE5i strongly suggests a potential protective effect of these
agents on renal function.
This ancillary PITCH-ER study leverages the PITCH-HF infrastructure and randomization,
adding only longitudinal collection of subjects' urine samples to 5 timepoints throughout
the study. With these urine samples collected, PITCH-ER will address 2 major
patient-oriented questions:
1. Does chronic tadalafil treatment slow the rate of GFR decline and/or modify the
development/progression of albuminuria vs placebo? To answer this question,
longitudinal measures of eGFR utilizing state-of-the-art equations that incorporate
serum creatinine and cystatin C and spot urine albumin-to-creatinine ratios (UACR) will
be measured.
2. Does PDE5i treatment reduce AKI frequency and/or the magnitude of urinary biomarker
changes reflecting subclinical renal injury vs placebo? An AKI adjudication committee
will monitor the incidence of AKI events and their severity using the Kidney Disease
Improving Global Outcomes (KDIGO) consensus criteria. Subclinical renal injury will be
detected using validated urinary biomarkers: neutrophil gelatinase-associated lipocalin
(NGAL) and kidney injury marker 1 (KIM-1).
Since 30% of the overall PITCH-HF population will likely have diabetes (which amplifies the
risk for renal injury in HF patients), PITCH-ER will repeat analyses in the population
stratified by baseline diabetes status as secondary endpoints.
Eligibility
Minimum age: 21 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- All subjects eligible for enrollment into the PITCH-HF parent trial are eligible to
enroll in this ancillary study (Refer to PITCH-HF NCT01910389 for specific
eligibility criteria)
Exclusion Criteria:
- Subjects who are not eligible for enrollment into the PITCH-HF parent trial may not
enroll in this ancillary study (Refer to PITCH-HF NCT01910389 for specific
eligibility criteria)
Locations and Contacts
Massachusetts General Hospital, Boston, Massachusetts 02114, United States
Additional Information
PITCH-HF Parent Study
Starting date: October 2013
Last updated: June 27, 2014
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