Heart FailurePhase 3PITCH-ERNCT01960153
Phosphodiesterase Type 5 Inhibition With Tadalafil Changes Outcomes in Heart Failure: Extent of Renal Damage
A Phase 3 study testing Tadalafil in people with Heart Failure and Pulmonary Hypertension, run by Massachusetts General Hospital at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 21 years and older
- Conditions the study is for
- Heart Failure, Pulmonary Hypertension
- What is being tested?
- Tadalafil
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2013to May 2018
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts General Hospital
Boston, Massachusetts, 02114
About this study
Official title: 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.
Read the 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.
- Conditions
- Heart Failure, Pulmonary Hypertension
- Being tested
- Tadalafil, Placebo
- Keywords
- Heart failure, Pulmonary hypertension, tadalafil, Phosphodiesterase Type 5 Inhibition
- Medical subject headings
- Heart Failure, Hypertension, Pulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TadalafilDrug
Also called Adcirca
Tadalafil tablets, 20 mg to 40 mg per day x 48 weeks
PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Tadalafil | Experimental | 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. Receives: Drug: Tadalafil |
| Placebo | Placebo comparator | 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in renal function
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)
Measured: Baseline to 48 months
Incidence of acute kidney injury (AKI) events (clinical and subclinical)
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).
Measured: Baseline to 48 months
Secondary outcomes (2)
Changes in renal function stratified by diabetes/no diabetes
As for the primary outcome, measurements will be eGFR and UACR
Measured: Baseline to 48 months
Incidence of AKI events stratified by diabetes/no diabetes
As for the primary outcome, AKI events will be adjudicated and N-GAL and KIM-1 will be measured
Measured: Baseline to 48 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Oct 2013 (estimated)
- Study startOct 2013
- Primary completionDec 2017 (estimated)
- Study completionMay 2018 (estimated)
Why it stopped: Award was ended by NIH for parent study
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), Carelon Research
- Responsible party
- Principal investigator, Ravi Thadhani, Massachusetts General Hospital
- Investigators
- Ravi I Thadhani, MD, MPH, Principal investigator, Massachusetts General HospitalIshir Bhan, MD, MPH, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01960153
- Sponsor's protocol ID
- 2013P001412
- Other IDs
- R01HL119155-01A1
- Acronym
- PITCH-ER
- Status last verified
- Sep 2017
- First submitted
- 8 Oct 2013
- Last updated
- 12 Sep 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 12 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phosphodiesterase Type 5 Inhibition With Tadalafil Changes Outcomes in Heart Failure: Extent of Renal Damage (PITCH-ER)
- ClinicalTrials.gov ID
- NCT01960153
- Acronym / sponsor ID
- PITCH-ER / 2013P001412
- Conditions
- Heart Failure, Pulmonary Hypertension
- Keywords
- Heart failure, Pulmonary hypertension, tadalafil, Phosphodiesterase Type 5 Inhibition
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Award was ended by NIH for parent study
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), Carelon Research
- Study start
- Oct 2013
- Primary completion
- Dec 2017 (estimated)
- Study completion
- May 2018 (estimated)
- First posted
- 10 Oct 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tadalafil | Experimental | Drug: TadalafilTadalafil 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. |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo 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. |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 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)
Key exclusion criteria (1 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TadalafilAlso: AdcircaTadalafil tablets, 20 mg to 40 mg per day x 48 weeks | Drug | Tadalafil |
| PlaceboPlacebo 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 |
Primary outcome
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)
Incidence of acute kidney injury (AKI) events (clinical and subclinical)
Time frame: Baseline to 48 months
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).
2 secondary outcomes
Changes in renal function stratified by diabetes/no diabetes
Time frame: Baseline to 48 months
Incidence of AKI events stratified by diabetes/no diabetes
Time frame: Baseline to 48 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Sep 2017.
- PITCH-HF Parent StudyLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ravi I Thadhani, MD, MPH principal investigator
Massachusetts General Hospital
Ishir Bhan, MD, MPH principal investigator
Massachusetts General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Tadalafil in people with Heart Failure and Pulmonary Hypertension, run by Massachusetts General Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 12 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in renal function (time frame: Baseline to 48 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Sep 2017.