- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01960153
Phosphodiesterase Type 5 Inhibition With Tadalafil Changes Outcomes in Heart Failure: Extent of Renal Damage (PITCH-ER)
Phosphodiesterase Type 5 Inhibition With Tadalafil Changes Outcomes in Heart Failure: Extent of Renal Damage (PITCH-ER)
Study Overview
Status
Conditions
Intervention / Treatment
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:
- 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.
- 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.
Study Type
Phase
- Phase 3
Contacts and Locations
Study Locations
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Massachusetts
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Boston, Massachusetts, United States, 02114
- Massachusetts General Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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.
|
Tadalafil tablets, 20 mg to 40 mg per day x 48 weeks
Other Names:
|
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.
|
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in renal function
Time Frame: Baseline to 48 months
|
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)
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Baseline to 48 months
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Incidence of acute kidney injury (AKI) events (clinical and subclinical)
Time Frame: Baseline to 48 months
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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).
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Baseline to 48 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Changes in renal function stratified by diabetes/no diabetes
Time Frame: Baseline to 48 months
|
As for the primary outcome, measurements will be eGFR and UACR
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Baseline to 48 months
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Incidence of AKI events stratified by diabetes/no diabetes
Time Frame: Baseline to 48 months
|
As for the primary outcome, AKI events will be adjudicated and N-GAL and KIM-1 will be measured
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Baseline to 48 months
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Ravi I Thadhani, MD, MPH, Massachusetts General Hospital
- Principal Investigator: Ishir Bhan, MD, MPH, Massachusetts General Hospital
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Heart Diseases
- Cardiovascular Diseases
- Vascular Diseases
- Respiratory Tract Diseases
- Lung Diseases
- Heart Failure
- Hypertension
- Hypertension, Pulmonary
- Molecular Mechanisms of Pharmacological Action
- Vasodilator Agents
- Urological Agents
- Enzyme Inhibitors
- Phosphodiesterase Inhibitors
- Phosphodiesterase 5 Inhibitors
- Tadalafil
Other Study ID Numbers
- 2013P001412
- R01HL119155-01A1 (U.S. NIH Grant/Contract)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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