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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This study has been withdrawn prior to enrollment.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

October 8, 2013
June 27, 2014
October 2013
December 2017   (final data collection date for primary outcome measure)
  • 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).
Same as current
Complete list of historical versions of study NCT01960153 on ClinicalTrials.gov Archive Site
  • 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
Same as current
Not Provided
Not Provided
 
Phosphodiesterase Type 5 Inhibition With Tadalafil Changes Outcomes in Heart Failure: Extent of Renal Damage
Phosphodiesterase Type 5 Inhibition With Tadalafil Changes Outcomes in Heart Failure: Extent of Renal Damage (PITCH-ER)

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.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
  • Heart Failure
  • Pulmonary Hypertension
  • Drug: Tadalafil
    Tadalafil tablets, 20 mg to 40 mg per day x 48 weeks
    Other Name: Adcirca
  • 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.
  • 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.
    Intervention: Drug: Tadalafil
  • 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.
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Withdrawn
0
May 2018
December 2017   (final data collection date for primary outcome measure)

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)
Both
21 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01960153
2013P001412, R01HL119155-01A1
Yes
Ravi Thadhani, Massachusetts General Hospital
Massachusetts General Hospital
  • National Heart, Lung, and Blood Institute (NHLBI)
  • New England Research Institutes
Principal Investigator: Ravi I Thadhani, MD, MPH Massachusetts General Hospital
Principal Investigator: Ishir Bhan, MD, MPH Massachusetts General Hospital
Massachusetts General Hospital
June 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP