Phosphodiesterase Type 5 Inhibition With Tadalafil Changes Outcomes in Heart Failure: Extent of Renal Damage (PITCH-ER)

This study has been withdrawn prior to enrollment.
(Award was ended by NIH for parent study)
Sponsor:
Collaborators:
New England Research Institutes
Information provided by (Responsible Party):
Ravi Thadhani, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT01960153
First received: October 8, 2013
Last updated: June 27, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Heart Failure
Pulmonary Hypertension
Drug: Tadalafil
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Phosphodiesterase Type 5 Inhibition With Tadalafil Changes Outcomes in Heart Failure: Extent of Renal Damage (PITCH-ER)

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Change in renal function [ Time Frame: Baseline to 48 months ] [ Designated as safety issue: No ]
    Between-group differences in changes from baseline in: (1a) eGFR using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and (1b) spot urine albumin-to-creatinine ratio (UACR)

  • Incidence of acute kidney injury (AKI) events (clinical and subclinical) [ Time Frame: Baseline to 48 months ] [ Designated as safety issue: No ]
    Impact of treatment on (2a) incidence of AKI events (adjudicated) based on new Kidney Disease Improving Global Outcomes criteria; and (2b) changes from baseline in the urine biomarkers of subclinical kidney injury: Neutrophil Gelatinase-Associated Lipocalin (NGAL) and Kidney Injury Marker 1 (KIM-1).


Secondary Outcome Measures:
  • Changes in renal function stratified by diabetes/no diabetes [ Time Frame: Baseline to 48 months ] [ Designated as safety issue: No ]
    As for the primary outcome, measurements will be eGFR and UACR

  • Incidence of AKI events stratified by diabetes/no diabetes [ Time Frame: Baseline to 48 months ] [ Designated as safety issue: No ]
    As for the primary outcome, AKI events will be adjudicated and N-GAL and KIM-1 will be measured


Enrollment: 0
Study Start Date: October 2013
Estimated Study Completion Date: May 2018
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tadalafil
Tadalafil is supplied in 20 mg tablets. Subjects will take 20 mg (one tablet) once per day and will be titrated to 40 mg (two tablets once per day) after one week. Subjects are on study drug for the duration of the trial.
Drug: Tadalafil
Tadalafil tablets, 20 mg to 40 mg per day x 48 weeks
Other Name: Adcirca
Placebo Comparator: Placebo
Placebo of tadalafil. Subjects will take one tablet once per day and will be titrated to two tablets once per day after one week. Subjects are on study drug for the duration of the trial.
Drug: Placebo
Placebo of tadalafil. Subjects will take one tablet once per day and will be titrated to two tablets once per day after one week. Subjects are on study drug for the duration of the trial.

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

Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01960153

Locations
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Massachusetts General Hospital
New England Research Institutes
Investigators
Principal Investigator: Ravi I Thadhani, MD, MPH Massachusetts General Hospital
Principal Investigator: Ishir Bhan, MD, MPH Massachusetts General Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: Ravi Thadhani, Chief, Division of Nephrology, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01960153     History of Changes
Other Study ID Numbers: 2013P001412, R01HL119155-01A1
Study First Received: October 8, 2013
Last Updated: June 27, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Massachusetts General Hospital:
Heart failure
Pulmonary hypertension
tadalafil
Phosphodiesterase Type 5 Inhibition

Additional relevant MeSH terms:
Heart Failure
Hypertension
Hypertension, Pulmonary
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Lung Diseases
Respiratory Tract Diseases
Tadalafil
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Vasodilator Agents
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 26, 2014