Re-evaluation of Optimal Re-synchronisation Therapy in Patients With Chronic Heart Failure

NCT ID: NCT03494933

Last Updated: 2023-08-03

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 959 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-09-01
• Study Completion Date: 2023-02-21

Brief Summary

The objective of the study is to demonstrate that in patients with chronic heart failure who receive optimal medical treatment for this condition and have indication for Cardiac Resynchronisation Therapy, the implantation of a pacemaker (index group) is not inferior to defibrillator (control group) with respect to all-cause mortality.

Detailed Description

Heart failure is a leading cause of death, hospitalisation, impaired quality of life and health expenditure. Symptoms and survival can be significantly improved by implantation of a device for Cardiac Resynchronisation Therapy (CRT). CRT devices are available as biventricular pacemakers (CRT-P) or as significantly more complex and cost-intensive biventricular defibrillators (CRT-D).

In patients who have previously experienced a life-threatening arrhythmia, the choice of the CRT-D (and not the CRT-P) is imperative but these are a small minority of patients. For the vast majority of patients receiving CRT therapy, there is currently considerable uncertainty as to whether the defibrillator function is needed and whether its benefits outweigh its risks. The defibrillator function may protect patients from sudden cardiac death. On the other hand, device-associated complications such as device infections appear to be increased; furthermore the defibrillator comes along with specific adverse events, particularly inappropriate shocks. These shocks are common and not only traumatic to patients (potentially leading to post-traumatic stress syndrome, anxiety disorders and depression), they also are negatively associated with overall survival.

The objective of the trial is to demonstrate that in patients with chronic heart failure who receive optimal medical treatment for this condition and have indication for CRT, the implantation of a CRT-P (index group) is not inferior to CRT-D (control group) with respect to all-cause mortality. Patients with an indication for CRT will be randomised to CRT-P or CRT-D.

RESET-CRT is an event-driven trial with a planned number of randomised and treated patients of at least n=1,356 (maximum of 2,004) and of 361 primary endpoints within an estimated median follow-up period of about 29 to 40 months.

No investigational medical product is defined to be used within RESET-CRT since only the therapeutic strategy (CRT-D versus CRT-P) is a pre-defined study treatment and allocated by random group (Proof of Strategy Trial). The devices to be implanted will be decided by the treating physician on the basis of the situation of the individual study patient and in line with local policies in routine clinical care.

Duration of study period:

Enrolment of 1,356 patients is expected to be completed within 52 months after inclusion of the first patient, i.e., by 31 December 2022. With an overall annual event rate between 9.0% and 12.5%, 361 primary endpoints will have occurred within 9 to 20 months of randomisation of the last patient (between 30 September 2023 and 31 August 2024). Under these circumstances, the total study duration will be between 62 and 73 months.

The Steering Committee of the study might prolong the recruitment period, for instance by 12 months, in the event of an unexpected slower recruitment rate or an overall event rate < 9.0% for the primary endpoint.

For individual patients, the expected median follow-up time is between 29 and 40 months, with a minimum between 9 and 20 months and a maximum between 61 and 72 months. Follow-up may be prolonged by 12 months in the event of a prolonged recruitment period.

Conditions

Chronic Heart Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

CRT-P group

Intervention: CRT-P implantation

Group Type: EXPERIMENTAL

CRT-P implantation

Intervention Type: PROCEDURE

Patients will be treated according to Optimal Medical Therapy defined by ESC Guidelines for treatment of patients with heart failure and will receive on top a CRT-P device.

CRT-D group

Intervention: CRT-D implantation

Group Type: ACTIVE_COMPARATOR

CRT-D implantation

Intervention Type: PROCEDURE

Patients will be treated according to Optimal Medical Therapy defined by ESC Guidelines for treatment of patients with heart failure and will receive on top a CRT-D device.

Interventions

CRT-P implantation

Patients will be treated according to Optimal Medical Therapy defined by ESC Guidelines for treatment of patients with heart failure and will receive on top a CRT-P device.

Intervention Type: PROCEDURE

CRT-D implantation

Patients will be treated according to Optimal Medical Therapy defined by ESC Guidelines for treatment of patients with heart failure and will receive on top a CRT-D device.

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Age ≥18 years.
• Symptomatic chronic heart failure due to ischemic or non-ischemic cardiomyopathy with NYHA class II, III or ambulatory IV.
• Reduced left ventricular ejection fraction ≤35% in transthoracic echocardiography (TTE) or cardiac magnetic resonance imaging (MRI) assessed verifiably within 4 weeks prior to or on the day of enrolment.
• On Optimal Medical Therapy (OMT) for at least 3 months prior to enrolment.
• Class I or IIa indication for implantation of a device for cardiac resynchronisation therapy (according to 2016 Guidelines of the European Society of Cardiology for the diagnosis and treatment of acute and chronic heart failure).
• Signed informed consent.

Exclusion Criteria

• Class I or IIa indication for implantation of an ICD for secondary prevention of sudden cardiac death and ventricular tachycardia (according to the 2015 Guidelines of the European Society of Cardiology for the management of patients with ven-tricular arrhythmias and the prevention of sudden cardiac death).
• Violation of Instruction For Use of the selected device by at least one of the random group treatments.
• Ventricular tachycardia induced in an electrophysiological study.
• Carrying any implanted cardiac pacemaker, defibrillator or CRT device.
• Unexplained syncope.
• Hospitalised with unstable heart failure with NYHA class IV within 1 month prior to enrolment.
• Acute coronary syndrome or cardiac revascularization therapy by coronary angioplasty or coronary artery bypass grafting within 6 weeks prior to enrolment.
• Cardiac valve surgery or percutaneous cardiac valvular intervention such as transcatheter aortic valve replacement or transcatheter mitral valve repair performed within 3 months prior to enrolment.
• Reversible non-ischemic cardiomyopathy such as acute viral myocarditis or discontinuation of alcohol in alcohol-induced heart disease.
• On the waiting list for heart transplant.
• Any disease that limits life expectancy to less than 2 years.
• Severe chronic renal disease (GFR<15 ml/min and/or the need for dialysis)
• Participation in another clinical trial, either within the past 3 months or still ongoing (participation in sub-studies connected to this trial and participation in observational studies permitted).
• Previous participation in RESET-CRT.
• Pregnant women or women of childbearing potential not on adequate birth control.
• Drug abuse or clinically manifest alcohol abuse.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Heart Center Leipzig - University Hospital

OTHER

Sponsor Role: collaborator

Helios Health Institute GmbH

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gerhard Hindricks, MD

Role: PRINCIPAL_INVESTIGATOR

Heart Center Leipzig - University Hospital

Locations

Helios Klinikum Aue

Aue, , Germany

Zentralklinik Bad Berka

Bad Berka, , Germany

Universitäts-Herzzentrum

Bad Krozingen, , Germany

Marienhaus Klinikum im Kreis Ahrweiler

Bad Neuenahr-Ahrweiler, , Germany

RHÖN-KLINIKUM Campus Bad Neustadt

Bad Neustadt A.d. Saale, , Germany

Herz- und Diabeteszentrum NRW - Universitätsklinik der Ruhr-Universität Bochum

Bad Oeynhausen, , Germany

Segeberger Kliniken

Bad Segeberg, , Germany

Maria-Hilf-Krankenhaus Bergheim

Bergheim, , Germany

Sana Klinikum Lichtenberg

Berlin, , Germany

Unfallkrankenhaus Berlin

Berlin, , Germany

Helios Klinikum Berlin-Buch

Berlin, , Germany

Jüdisches Krankenhaus Berlin

Berlin, , Germany

Charité Campus Virchow-Klinikum

Berlin, , Germany

Vivantes Klinikum Spandau

Berlin, , Germany

Helios Klinikum Emil von Behring

Berlin, , Germany

Immanuel Klinikum Bernau - Herzzentrum Brandenburg

Bernau bei Berlin, , Germany

Klinikum Bielefeld

Bielefeld, , Germany

Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil

Bochum, , Germany

Augusta Kliniken Bochum

Bochum, , Germany

Universitätsklinikum Bonn

Bonn, , Germany

Knappschaftskrankenhaus Bottrop

Bottrop, , Germany

REGIOMED-KLINIKEN Klinikum Coburg

Coburg, , Germany

St. Vinzenz-Hospital

Cologne, , Germany

Herzzentrum Uniklinik Köln

Cologne, , Germany

Krankenhaus Porz am Rhein

Cologne, , Germany

Carl-Thiem-Klinikum

Cottbus, , Germany

Helios Amper-Klinikum Dachau

Dachau, , Germany

Klinikum Lippe Detmold

Detmold, , Germany

St.-Johannes-Hospital Dortmund

Dortmund, , Germany

Herz Zentrum Westfalen - Knappschaftskrankenhaus Dortmund

Dortmund, , Germany

Praxisklinik Herz und Gefäße

Dresden, , Germany

Herzzentrum Dresden Universitätsklinik

Dresden, , Germany

Helios Klinikum Erfurt

Erfurt, , Germany

Hermann-Josef-Krankenhaus Erkelenz

Erkelenz, , Germany

Universitätsklinikum Erlangen

Erlangen, , Germany

Contilia Herz- und Gefäßzentrum

Essen, , Germany

Ev.-Luth. Diakonissenanstalt zu Flensburg

Flensburg, , Germany

Universitätsklinikum Frankfurt

Frankfurt am Main, , Germany

Kreiskrankenhaus Freiberg

Freiberg, , Germany

Klinikum Fulda

Fulda, , Germany

UKGM - Universitätsklinikum Gießen

Giessen, , Germany

Asklepios Harzklinik Goslar

Goslar, , Germany

Helios Klinikum Gotha

Gotha, , Germany

Universitätsmedizin Göttingen

Göttingen, , Germany

Universitätsmedizin Greifswald

Greifswald, , Germany

Klinikum Gütersloh gGmbH

Gütersloh, , Germany

Evangelisches Krankenhaus Hagen-Haspe

Hagen, , Germany

Krankenhaus Martha-Maria Halle-Dölau

Halle, , Germany

Universitätsklinikum Halle (Saale)

Halle, , Germany

Universitätsklinikum Hamburg-Eppendorf (UKE)

Hamburg, , Germany

Asklepios Kliniken Hamburg GmbH - Asklepios Klinikum Harburg

Hamburg, , Germany

Asklepios Kliniken Hamburg GmbH

Hamburg, , Germany

Albertinen Herz- und Gefäßzentrum - Albertinen Krankenhaus

Hamburg, , Germany

St. Marien-Hospital Hamm

Hamm, , Germany

Medizinische Hochschule Hannover (MHH)

Hanover, , Germany

Universitätsklinikum Heidelberg

Heidelberg, , Germany

Helios St. Marienberg Klinik Helmstedt

Helmstedt, , Germany

Oberhavel Kliniken

Hennigsdorf, , Germany

Helios Klinikum Hildesheim

Hildesheim, , Germany

Universitätsklinikum des Saarlandes

Homburg, , Germany

Klinikum Ingolstadt

Ingolstadt, , Germany

Universitätsklinikum Jena

Jena, , Germany

Westpfalz-Klinikum GmbH

Kaiserslautern, , Germany

Städtisches Klinikum Karlsruhe

Karlsruhe, , Germany

B. Braun Ambulantes Herzzentrum Kassel

Kassel, , Germany

Universitätsklinikum Schleswig-Holstein Campus Kiel

Kiel, , Germany

Städtisches Krankenhaus Kiel

Kiel, , Germany

Katholisches Klinikum Koblenz - Montabaur

Koblenz, , Germany

Helios Klinikum Krefeld

Krefeld, , Germany

Universitätsklinikum Leipzig

Leipzig, , Germany

Herzzentrum Leipzig

Leipzig, , Germany

Klinikum Leverkusen

Leverkusen, , Germany

Cardio Centrum Ludwigburg

Ludwigsburg, , Germany

Universitätsklinikum Schleswig-Holstein

Lübeck, , Germany

Klinikum Lüdenscheid

Lüdenscheid, , Germany

St.-Marien-Hospital Lünen

Lünen, , Germany

Universitätsklinikum Magdeburg

Magdeburg, , Germany

Johannes Wesling Klinikum Minden

Minden, , Germany

Ev. Krankenhaus Bethesda Mönchengladbach

Mönchengladbach, , Germany

Kliniken Maria Hilf

Mönchengladbach, , Germany

Städtische Kliniken Mönchengladbach - Elisabeth-Krankenhaus Rheydt

Mönchengladbach, , Germany

Klinik Augustinum

München, , Germany

LMU Klinikum

München, , Germany

Technische Universität München

München, , Germany

München Klinik Neuperlach

München, , Germany

Universitätsklinikum Münster

Münster, , Germany

Havelland Kliniken

Nauen, , Germany

Marienhaus Klinikum St. Elisabeth Neuwied

Neuwied, , Germany

Klinikum Nürnberg Süd

Nuremberg, , Germany

St. Vincenz-Krankenhaus

Paderborn, , Germany

Helios Vogtland-Klinikum Plauen

Plauen, , Germany

Harzklinikum Dorothea Christiane Erxleben Klinikum Quedlinburg

Quedlinburg, , Germany

Elblandklinikum Riesa

Riesa, , Germany

Universitätsmedizin Rostock

Rostock, , Germany

Asklepios Klinikum Uckermark

Schwedt, , Germany

Helios Kliniken Schwerin

Schwerin, , Germany

Helios Klinikum Siegburg

Siegburg, , Germany

Marien Kliniken

Siegen, , Germany

Diakonie Klinikum Jung-Stilling

Siegen, , Germany

Krankenhaus Maria-Hilf Stadtlohn Klinikum Westmünsterland

Stadtlohn, , Germany

Johanniter-Krankenhaus Genthin-Stendal

Stendal, , Germany

Robert-Bosch-Krankenhaus

Stuttgart, , Germany

Krankenhaus der Barmherzigen Brüder Trier

Trier, , Germany

Klinikum Landkreis Tuttlingen

Tuttlingen, , Germany

Universitätsklinikum Ulm

Ulm, , Germany

Aller-Weser-Klinik - Krankenhaus Verden

Verden an der Aller, , Germany

Schwarzwald-Baar Klinikum

Villingen-Schwenningen, , Germany

Helios Klinikum Warburg GmbH

Warburg, , Germany

Sophien- und Hufeland-Klinikum

Weimar, , Germany

Rems-Murr-Klinikum Winnenden

Winnenden, , Germany

Helios Universitätsklinikum Wuppertal

Wuppertal, , Germany

Universitätsklinikum Würzburg

Würzburg, , Germany

Heinrich-Braun-Klinikum

Zwickau, , Germany

Countries

Germany

References

Chatterjee NA, Poole JE. Cardiac Resynchronization Therapy in Nonischemic Cardiomyopathy: To D or P? JACC Heart Fail. 2021 Jun;9(6):450-452. doi: 10.1016/j.jchf.2021.04.001. Epub 2021 May 12. No abstract available.

Reference Type: DERIVED

PMID: 33992569 (View on PubMed)

Other Identifiers

HRC048864

Identifier Type: -

Identifier Source: org_study_id