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

Chronic Heart Failure Clinical Trial

— RESET-CRT  

Official title:

Re-evaluation of Optimal Re-synchronisation Therapy in Patients With Chronic Heart Failure - An Investigator-initiated, Event-driven, Prospective, Parallel-group, Randomised, Open, Blinded Outcome Assessment (PROBE), Multi-centre Trial Without Investigational Medical Products (Proof of Strategy Trial)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03494933
• Other study ID #: HRC048864
• Status: Terminated
• Phase: N/A
• Start date: September 1, 2018
• Est. completion date: February 21, 2023

Study information

• Verified date: August 2022
• Source: Helios Health Institute GmbH
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 959
• Est. completion date: February 21, 2023
• Est. primary completion date: February 21, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Heart Failure
• Heart Failure

Intervention

Procedure:
• 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.
• 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.

Locations

Country	Name	City	State
Germany	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	Charité Campus Virchow-Klinikum	Berlin
Germany	Helios Klinikum Berlin-Buch	Berlin
Germany	Helios Klinikum Emil von Behring	Berlin
Germany	Jüdisches Krankenhaus Berlin	Berlin
Germany	Sana Klinikum Lichtenberg	Berlin
Germany	Unfallkrankenhaus Berlin	Berlin
Germany	Vivantes Klinikum Spandau	Berlin
Germany	Immanuel Klinikum Bernau - Herzzentrum Brandenburg	Bernau bei Berlin
Germany	Klinikum Bielefeld	Bielefeld
Germany	Augusta Kliniken Bochum	Bochum
Germany	Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil	Bochum
Germany	Universitätsklinikum Bonn	Bonn
Germany	Knappschaftskrankenhaus Bottrop	Bottrop
Germany	REGIOMED-KLINIKEN Klinikum Coburg	Coburg
Germany	Carl-Thiem-Klinikum	Cottbus
Germany	Helios Amper-Klinikum Dachau	Dachau
Germany	Klinikum Lippe Detmold	Detmold
Germany	Herz Zentrum Westfalen - Knappschaftskrankenhaus Dortmund	Dortmund
Germany	St.-Johannes-Hospital Dortmund	Dortmund
Germany	Herzzentrum Dresden Universitätsklinik	Dresden
Germany	Praxisklinik Herz und Gefäße	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 (Saale)
Germany	Universitätsklinikum Halle (Saale)	Halle (Saale)
Germany	Albertinen Herz- und Gefäßzentrum - Albertinen Krankenhaus	Hamburg
Germany	Asklepios Kliniken Hamburg GmbH	Hamburg
Germany	Asklepios Kliniken Hamburg GmbH - Asklepios Klinikum Harburg	Hamburg
Germany	Universitätsklinikum Hamburg-Eppendorf (UKE)	Hamburg
Germany	St. Marien-Hospital Hamm	Hamm
Germany	Medizinische Hochschule Hannover (MHH)	Hannover
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	Städtisches Krankenhaus Kiel	Kiel
Germany	Universitätsklinikum Schleswig-Holstein Campus Kiel	Kiel
Germany	Katholisches Klinikum Koblenz - Montabaur	Koblenz
Germany	Herzzentrum Uniklinik Köln	Köln
Germany	Krankenhaus Porz am Rhein	Köln
Germany	St. Vinzenz-Hospital	Köln
Germany	Helios Klinikum Krefeld	Krefeld
Germany	Herzzentrum Leipzig	Leipzig
Germany	Universitätsklinikum Leipzig	Leipzig
Germany	Klinikum Leverkusen	Leverkusen
Germany	Universitätsklinikum Schleswig-Holstein	Lübeck
Germany	Klinikum Lüdenscheid	Lüdenscheid
Germany	Cardio Centrum Ludwigburg	Ludwigsburg
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	München Klinik Neuperlach	München
Germany	Technische Universität München	München
Germany	Universitätsklinikum Münster	Münster
Germany	Havelland Kliniken	Nauen
Germany	Marienhaus Klinikum St. Elisabeth Neuwied	Neuwied
Germany	Klinikum Nürnberg Süd	Nürnberg
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/Oder
Germany	Helios Kliniken Schwerin	Schwerin
Germany	Helios Klinikum Siegburg	Siegburg
Germany	Diakonie Klinikum Jung-Stilling	Siegen
Germany	Marien Kliniken	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
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

Sponsors (2)

Lead Sponsor	Collaborator
Helios Health Institute GmbH	Heart Center Leipzig - University Hospital

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time from randomisation to the occurrence of all-cause death	Time from randomisation to the occurrence of all-cause death	Randomization to end of study (event-driven, expected about 9 to 20 months after last patient in)
Secondary	Time from randomisation to death from cardiac causes	Time from randomisation to death from cardiac causes	Randomization to end of study (event-driven, expected about 9 to 20 months after last patient in)
Secondary	Time from randomisation to sudden cardiac death	Time from randomisation to sudden cardiac death	Randomization to end of study (event-driven, expected about 9 to 20 months after last patient in)
Secondary	Time from randomisation to life-threatening arrhythmias	Time from randomisation to life-threatening arrhythmias	Randomization to end of study (event-driven, expected about 9 to 20 months after last patient in)
Secondary	Time from randomisation to first composite of Major Adverse Cardiac Event (MACE)	Time from randomisation to first composite of Major Adverse Cardiac Event (MACE)	Randomization to end of study (event-driven, expected about 9 to 20 months after last patient in)
Secondary	Time from randomisation to first hospitalisation for cardiovascular reasons	Time from randomisation to first hospitalisation for cardiovascular reasons	Randomization to end of study (event-driven, expected about 9 to 20 months after last patient in)
Secondary	Nights spent in hospital for cardiovascular reasons per year of follow-up	Number of nights spent in hospital is calculated as time difference in days from hospital discharge to hospital admission. All hospital stays are serious adverse event by definition and will be assessed by an independent Endpoint Review Committee. The Endpoint Review Committee will also evaluate if a hospital stay for cardiovascular reasons is given. Per year of follow-up refers to a calculated number related to total follow-up duration of each patient normalised to years of follow-up.	Randomization to end of study (event-driven, expected about 9 to 20 months after last patient in)
Secondary	Number of hospital readmissions for cardiovascular reasons after randomisation	Number of hospital readmissions for cardiovascular reasons after randomisation	Randomization to end of study (event-driven, expected about 9 to 20 months after last patient in)
Secondary	Changes in quality of life (EQ-5D) comparing inclusion/enrolment with 12 and 24 months	Quality of life will be measured using the European Quality of life 5 Dimension (EQ5D) questionnaire including its visual-analogue scale (Scores range from 0-100 where 0 is the worst score).	at baseline, 12 and 24 months after randomisation
Secondary	Total cost of treatment as compound endpoint of MACEs, number of hospital days for cardiovascular reasons and ambulatory visits for cardiovascular reasons	otal cost of treatment as compound endpoint of MACEs, number of hospital days for cardiovascular reasons and ambulatory visits for cardiovascular reasons	Randomization to end of study (event-driven, expected about 9 to 20 months after last patient in)