Heart Failure (HF)Phase 4STOP-CRTNCT02200822
Systematic Withdrawal of Neurohumoral Blocker Therapy in Optimally Responding CRT Patients
A Phase 4 study testing beta blockers and RAAS blockers in people with Heart Failure (HF), run by Hasselt University at 1 site in Belgium.
Trial summary
The primary objective of this study is to demonstrate that in patients with recuperated/normalized left ventricular function, defined as an ejection fraction (EF) ≥ 50%, after implantation of cardiac resynchronization therapy, device treatment is sufficient and neurohumoral blocker therapy can safely be withdrawn Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure (HF)
- What is being tested?
- beta blockers and RAAS blockers
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteBelgium
- Study dates
- Jul 2014to Feb 2019
- Phase
- Phase 4
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ≥18 years
- CRT implantation
- based on class I recommendations of ESC (European society of CArdiology) guidelines:
- Left bundle branch block (LBBB) with QRS duration >150 ms and left ventricular ejection fraction (LVEF) ≤35% who remained NYHA functional class II, III and ambulatory IV despite adequate medical treatment
- LBBB with QRS duration 120-150 ms and LVEF ≤ 35% who remain in NYHA functional class II, III and ambulatory IV despite adequate medical treatment
- At the moment of inclusion: ≥ 6 months after implantation
- At the moment of inclusion: normalised LVEF (≥ 50%), LVIDD/BSA (left ventricular internal diastolic diameter indexed to body surface area) ≤3.2 cm/m²(woman) en ≤3.1 cm/m² (men) or LVDV/BSA (left ventricular diastolic volume indexed to body surface area) ≤75 ml/m² (women) or ≤75 ml/m² (men)
- euvolemic clinical state and functioning in NYHA class I
Who cannot join
- contraindication for withdrawal of ACE-I/ARB such as diabetic nephropathy and proteinuria > 1g / 24 h
- severe ventricular arrythmia (sustained VT or ventricular fibrillation) occuring at the time LV function was normalized
- ischemic cardiomyopathy with evidence of scarring (scarring on MRI or severe hypokinesia/akinesia in >1 LV wall segment on echocardiography)
- known severe coronary atherosclerosis (stenosis ≥ 80%)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Systematic Withdrawal of Neurohumoral Blocker Therapy in Optimally Responding Patients to Cardiac Resynchronization Therapy: the STOP-CRT Trial
The primary objective of this study is to demonstrate that in patients with recuperated/normalized left ventricular function, defined as an ejection fraction (EF) ≥ 50%, after implantation of cardiac resynchronization therapy, device treatment is sufficient and neurohumoral blocker therapy can safely be withdrawn
- Conditions
- Heart Failure (HF)
- Being tested
- beta blockers, RAAS blockers
- Keywords
- neurohumoral blocker therapy, renin-angiotensin-aldosterone system (RAAS), RAAS-blocker, beta blocker, spironolactone, angiotensin converting enzyme inhibitor (ACE-I), angiotensin receptor blocker (ARB), cardiac resynchronization therapy (CRT), heart failure, dyssynchrony, left bundle branch block
- Medical subject headings
- Heart Failure, Bundle-Branch Block
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
beta blockersDrug
RAAS blockersDrug
RAAS blockers (combination of ACE-I/ARB and a mineralocorticoid receptor antagonist)
| Study group | Role | What they receive |
|---|---|---|
| non-intervention arm | No intervention | continuation of neurohumoral blocker therapy based on maximum tolerated guideline recommended dose (this group is the control arm for as well withdrawal of beta blocker therapy as withdrawal of RAAS blocker therapy) |
| withdrawal of beta blockers | Active comparator | Intervention arm with systematic withdrawal of beta blocker therapy at a reverse sequence of guideline recommended uptitration.
(this group is the experimental arm for beta blocker withdrawal. This group receives no intervention with regards to the withdrawal of RAAS blockade). Per 2 weeks:
* bisoprolol: 10mg/d → 5 mg/d → 2,5 mg/d → 1,25 mg/d stop
* metoprolol: 200 mg/d → 100 mg/d → 50 mg/d → 25 mg/d → stop
* nebivolol: 10mg/d → 5 mg/d → 2,5 mg/d → 1,25 mg/d stop
* carvedilol: 50 mg bid → 25 mg bid → 12,5 mg bid → 6,25 mg bid → stop Receives: Drug: beta blockers |
| withdrawal of RAAS blockers | Active comparator | intervention arm with systematic withdrawal of spironolactone followed by withdrawal of ACE-I/ARB at a reverse sequence of guideline recommended uptitration (this group receives no intervention regarding the withdrawal of beta blockers. This group is the experimental arm for withdrawal of RAAS blockers)
* first spironolactone/eplerenone: per two weeks: 25 mg/d→12,5 mg/d → stop
* after 2 weeks stop spironolactone/eplerenone start withdrawal of ACE-I/ARB per two weeks:
* captopril: 50 mg tid→25 mg tid→12,5 mg tid→6,25 mg tid→stop
* enalapril: 10 mg bid→5 mg bid→2,5 mg bid→1,25 mg bid→stop
* lisinopril: 20 mg/d→10 mg/d→5 mg/d→2,5 mg/d→stop
* ramipril: 10 mg/d→5 mg/d→2,5 mg/d→1,25 mg/d→stop
* candesartan: 32 mg/d→16 mg/d→8 mg/d→4 m/d→stop
* valsartan: 160 mg bid→80 mg bid→40 mg bid→20 mg bid→stop Receives: Drug: RAAS blockers |
| withdrawal of RAAS - and beta blockers | Active comparator | intervention arm with systematic withdrawal of spironolactone, secondly ACE-I/ARB and finally beta blockers. (this group is the experimental group for both study interventions (withdrawal of beta blockers and RAAS blockers)
* First: spironolactone/eplerenone cfr reduction schedule supra
* After 2 weeks of stop spironolactone withdrawal of ACE-I or ARB cfr reduction schedule supra
* After 2 weeks of stop ACE-I/ARB withdrawal of beta blocker cfr reduction schedule supra Receives: Drug: beta blockers; Drug: RAAS blockers |
What is being measured
The primary outcome is the main question the study is designed to answer.
a > 15% increase in left ventricular end systolic volume
Measured: at 12 months
Secondary outcomes (3)
- Incidence of HF related hospitalizations defined as admission to hospital / presentation to emergency room with need for parental therapy
Measured: at 12 months
All cause mortality
Measured: at 12 months
VO2 max change
Measured: at 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jul 2014 (estimated)
- Study startJul 2014
- Primary completionFeb 2019
- Study completionFeb 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Heart Failure (HF)Studies of the same condition, open and under way.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hasselt University
- Sponsor type
- University, hospital or other
- Collaborators
- Ziekenhuis Oost-Limburg
- Responsible party
- Principal investigator, Wilfried Mullens, MD PhD, Hasselt University
- Investigators
- Petra Nijst, MD, Principal investigator, Ziekenhuis Oost-Limburg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02200822
- Sponsor's protocol ID
- ZOL-STOP-CRT
- Acronym
- STOP-CRT
- Status last verified
- Jul 2019
- First submitted
- 24 Jul 2014
- Last updated
- 1 Aug 2019
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Nijst P, Martens P, Dauw J, Tang WHW, Bertrand PB, Penders J, Bruckers L, Voros G, Willems R, Vandervoort PM, Dupont M, Mullens W. Withdrawal of Neurohumoral Blockade After Cardiac Resynchronization Therapy. J Am Coll Cardiol. 2020 Mar 31;75(12):1426-1438. doi: 10.1016/j.jacc.2020.01.040.
PubMed 32216911
Study at a glance
From the registry record, last updated by the sponsor on 1 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Systematic Withdrawal of Neurohumoral Blocker Therapy in Optimally Responding Patients to Cardiac Resynchronization Therapy: the STOP-CRT Trial
- ClinicalTrials.gov ID
- NCT02200822
- Acronym / sponsor ID
- STOP-CRT / ZOL-STOP-CRT
- Conditions
- Heart Failure (HF)
- Keywords
- neurohumoral blocker therapy, renin-angiotensin-aldosterone system (RAAS), RAAS-blocker, beta blocker, spironolactone, angiotensin converting enzyme inhibitor (ACE-I), angiotensin receptor blocker (ARB), cardiac resynchronization therapy (CRT)
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- Hasselt UniversityUniversity, hospital or other
- Collaborators
- Ziekenhuis Oost-Limburg
- Study start
- Jul 2014
- Primary completion
- Feb 2019 (actual)
- Study completion
- Feb 2019 (actual)
- First posted
- 25 Jul 2014 (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.
The primary objective of this study is to demonstrate that in patients with recuperated/normalized left ventricular function, defined as an ejection fraction (EF) ≥ 50%, after implantation of cardiac resynchronization therapy, device treatment is sufficient and neurohumoral blocker therapy can safely be withdrawn
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| non-intervention arm | No intervention | –continuation of neurohumoral blocker therapy based on maximum tolerated guideline recommended dose (this group is the control arm for as well withdrawal of beta blocker therapy as withdrawal of RAAS blocker therapy) |
| withdrawal of beta blockers | Active comparator | Drug: beta blockersIntervention arm with systematic withdrawal of beta blocker therapy at a reverse sequence of guideline recommended uptitration. (this group is the experimental arm for beta blocker withdrawal. This group receives no intervention with regards to the withdrawal of RAAS blockade). Per 2 weeks: * bisoprolol: 10mg/d → 5 mg/d → 2,5 mg/d → 1,25 mg/d stop * metoprolol: 200 mg/d → 100 mg/d → 50 mg/d → 25 mg/d → stop * nebivolol: 10mg/d → 5 mg/d → 2,5 mg/d → 1,25 mg/d stop * carvedilol: 50 mg bid → 25 mg bid → 12,5 mg bid → 6,25 mg bid → stop |
| withdrawal of RAAS blockers | Active comparator | Drug: RAAS blockersintervention arm with systematic withdrawal of spironolactone followed by withdrawal of ACE-I/ARB at a reverse sequence of guideline recommended uptitration (this group receives no intervention regarding the withdrawal of beta blockers. This group is the experimental arm for withdrawal of RAAS blockers) * first spironolactone/eplerenone: per two weeks: 25 mg/d→12,5 mg/d → stop * after 2 weeks stop spironolactone/eplerenone start withdrawal of ACE-I/ARB per two weeks: * captopril: 50 mg tid→25 mg tid→12,5 mg tid→6,25 mg tid→stop * enalapril: 10 mg bid→5 mg bid→2,5 mg bid→1,25 mg bid→stop * lisinopril: 20 mg/d→10 mg/d→5 mg/d→2,5 mg/d→stop * ramipril: 10 mg/d→5 mg/d→2,5 mg/d→1,25 mg/d→stop * candesartan: 32 mg/d→16 mg/d→8 mg/d→4 m/d→stop * valsartan: 160 mg bid→80 mg bid→40 mg bid→20 mg bid→stop |
| withdrawal of RAAS - and beta blockers | Active comparator | Drug: beta blockers, Drug: RAAS blockersintervention arm with systematic withdrawal of spironolactone, secondly ACE-I/ARB and finally beta blockers. (this group is the experimental group for both study interventions (withdrawal of beta blockers and RAAS blockers) * First: spironolactone/eplerenone cfr reduction schedule supra * After 2 weeks of stop spironolactone withdrawal of ACE-I or ARB cfr reduction schedule supra * After 2 weeks of stop ACE-I/ARB withdrawal of beta blocker cfr reduction schedule supra |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- ≥18 years
- CRT implantation
- At the moment of inclusion: ≥ 6 months after implantation
- At the moment of inclusion: normalised LVEF (≥ 50%), LVIDD/BSA (left ventricular internal diastolic diameter indexed to body surface area) ≤3.2 cm/m²(woman) en ≤3.1 cm/m² (men) or LVDV/BSA (left ventricular diastolic volume indexed to body surface area) ≤75 ml/m² (women) or ≤75 ml/m² (men)
- euvolemic clinical state and functioning in NYHA class I
Key exclusion criteria (4 listed)
- contraindication for withdrawal of ACE-I/ARB such as diabetic nephropathy and proteinuria > 1g / 24 h
- severe ventricular arrythmia (sustained VT or ventricular fibrillation) occuring at the time LV function was normalized
- ischemic cardiomyopathy with evidence of scarring (scarring on MRI or severe hypokinesia/akinesia in >1 LV wall segment on echocardiography)
- known severe coronary atherosclerosis (stenosis ≥ 80%)
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 |
|---|---|---|
| beta blockers | Drug | withdrawal of RAAS - and beta blockers, withdrawal of beta blockers |
| RAAS blockersRAAS blockers (combination of ACE-I/ARB and a mineralocorticoid receptor antagonist) | Drug | withdrawal of RAAS - and beta blockers, withdrawal of RAAS blockers |
Primary outcome
a > 15% increase in left ventricular end systolic volume
Time frame: at 12 months
3 secondary outcomes
- Incidence of HF related hospitalizations defined as admission to hospital / presentation to emergency room with need for parental therapy
Time frame: at 12 months
All cause mortality
Time frame: at 12 months
VO2 max change
Time frame: at 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Aug 2019.
- Derived from this study: PubMed 32216911Nijst P, Martens P, Dauw J, Tang WHW, Bertrand PB, Penders J, Bruckers L, Voros G, Willems R, Vandervoort PM, Dupont M, Mullens W. Withdrawal of Neurohumoral Blockade After Cardiac Resynchronization Therapy. J Am Coll Cardiol. 2020 Mar 31;75(12):1426-1438. doi: 10.1016/j.jacc.2020.01.040.
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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.
Petra Nijst, MD principal investigator
Ziekenhuis Oost-Limburg
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing beta blockers and RAAS blockers in people with Heart Failure (HF), run by Hasselt University at 1 site in Belgium.
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 8 inclusion and 4 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: finished, as of the sponsor's last update on 1 Aug 2019. 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 Belgium. 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. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
a > 15% increase in left ventricular end systolic volume (time frame: at 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02200822, which also lists 1 linked publication.
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 1 Aug 2019.