Cardiomyopathy, Dilated, 3B Clinical Trial
— CRT-REALITYOfficial title:
CRT-P or CRT-D in Patients With Dilated Cardiomyopathy and Heart Failure Without LGE-CMR High-risk Markers
The ICD-Reality study is a non-commercial, investigator-led, multicenter, prospective,
randomized, controlled trial. We aim to determine the effect of CRT-D or CRT-P implantation
in non-ischemic cardiomyopathy and heart failure patients.
The reason why we initiated this trial is the lack of evidence-based treatment for the
significant number of these patients. In these patients, 5-year mortality remains as high as
20% despite recent therapeutic advances. Based on currently available evidence, because of a
significant decrease in mortality due to modern pharmacotherapy, it is not certain which of
these patients should receive a CRT-P and who should receive a CRT-D. No dedicated and
adequately powered trial has addressed this important question.
We hypothesize that patients with symptomatic HF, LVEF ≤35%, without left ventricular
mid-wall fibrosis on LGE-CMR, will not benefit from CRT-D implantation compared with CRT-P
only implantation.
If our hypothesis is confirmed, this could provide evidence for the management of these
patients with a significant impact on common daily praxis and health care expenditures.
We aim to enroll 600 patients in the trial. 924 patients are needed to be screened for these
600 patients to be randomized.
Patients with non-ischemic HF visiting an out-patient department and possibly eligible for
the trial will have their pharmacotherapy optimized.
Patients with a significant amount of fibrosis will be excluded from the study and treated
according to local practice with an emphasis on ICD implantation to prevent SCD.
After fulfilling all eligibility criteria, including maximally tolerated pharmacotherapy,
subjects will be randomized by the physicians who enrolled them in a 1:1 ratio to receive
CRT-D or CRT-P implantation.
All patients will be followed-up for at least 3 years after the implantation.
Status | Not yet recruiting |
Enrollment | 924 |
Est. completion date | January 2026 |
Est. primary completion date | January 2026 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 99 Years |
Eligibility |
Inclusion Criteria: - = 18 years of age at the time of screening - Documented non-ischemic HF with an LVEF = 35 - QRS=130ms; NYHA class II-IV - Signed written informed consent - NT-proBNP above 200 pg/ml Exclusion Criteria: - Uncorrected congenital heart disease or valve obstruction - obstructive cardiomyopathy - active myocarditis - constrictive pericarditis - untreated hypothyroidism or hyperthyroidism - adrenal insufficiency - active vasculitis due to collagen vascular disease - Presence on the urgent waiting list for a heart transplant (UNOS category 1A or 1B, or equivalent) - Patients on the non-urgent waiting list for a heart transplant (UNOS category 2 or 7, or equivalent) are eligible for inclusion in the study - Recipient of any major organ transplant (e.g., lung, liver, heart) - Receiving or has received cytotoxic or cytostatic chemotherapy and/or radiation therapy for treatment of a malignancy within 6 month before randomization or clinical evidence of current malignancy, with the following exceptions: basal or squamous cell carcinoma of the skin, cervical intraepithelial neoplasia, prostate cancer (if stable localized disease, with a life expectancy of > 2.5 years in the opinion of the investigator) - Known to be human immunodeficiency virus positive with an expected survival of less than 5 years due to HIV - Chronic kidney disease with glomerular filtration rate <30 ml/min - Chronic dialysis treatment - Recent (within 3 months) history of alcohol or illicit drug abuse disorder, based on self-report - Any condition (e.g., psychiatric illness) or situation that, in the investigator's opinion, could put the subject at significant risk, confound the study results, or interfere significantly with the subject's participation in the study - Unwilling to participate Additional information related to inclusion and exclusion criteria: - The qualifying LVEF and NT-proBNP level has to be measured after a maximal tolerated pharmacotherapy of heart failure has been achieved. - A non-ischemic cause of HF has to be determined by coronary angiography. Patients could be included even if they will have one or two coronary arteries with stenosis, if the extent of coronary artery disease will not be considered to be sufficient to account for the reduced LVEF. Patients with a significant coronary heart disease (CAD) will be excluded. - Patients with an existing conventional pacemaker could be included if they will be willing to have the device changed or upgraded. - Patients with any form of atrial fibrillation will not be excluded. |
Country | Name | City | State |
---|---|---|---|
Czechia | University hospital Olomouc | Olomouc | Ceská Republika |
Lead Sponsor | Collaborator |
---|---|
University Hospital Olomouc |
Czechia,
Bänsch D, Antz M, Boczor S, Volkmer M, Tebbenjohanns J, Seidl K, Block M, Gietzen F, Berger J, Kuck KH. Primary prevention of sudden cardiac death in idiopathic dilated cardiomyopathy: the Cardiomyopathy Trial (CAT). Circulation. 2002 Mar 26;105(12):1453-8. — View Citation
Bardy GH, Lee KL, Mark DB, Poole JE, Packer DL, Boineau R, Domanski M, Troutman C, Anderson J, Johnson G, McNulty SE, Clapp-Channing N, Davidson-Ray LD, Fraulo ES, Fishbein DP, Luceri RM, Ip JH; Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) Investigators. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med. 2005 Jan 20;352(3):225-37. Erratum in: N Engl J Med. 2005 May 19;352(20):2146. — View Citation
Barra S, Providência R, Boveda S, Duehmke R, Narayanan K, Chow AW, Piot O, Klug D, Defaye P, Gras D, Deharo JC, Milliez P, Da Costa A, Mondoly P, Gonzalez-Panizo J, Leclercq C, Heck P, Virdee M, Sadoul N, Le Heuzey JY, Marijon E. Device complications with addition of defibrillation to cardiac resynchronisation therapy for primary prevention. Heart. 2018 Sep;104(18):1529-1535. doi: 10.1136/heartjnl-2017-312546. Epub 2018 Mar 14. — View Citation
Bristow MR, Saxon LA, Boehmer J, Krueger S, Kass DA, De Marco T, Carson P, DiCarlo L, DeMets D, White BG, DeVries DW, Feldman AM; Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) Investigators. Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med. 2004 May 20;350(21):2140-50. — View Citation
Dichtl W, Wolber T, Paoli U, Brüllmann S, Stühlinger M, Berger T, Spuller K, Strasak A, Pachinger O, Haegeli LM, Duru F, Hintringer F. Appropriate therapy but not inappropriate shocks predict survival in implantable cardioverter defibrillator patients. Clin Cardiol. 2011 Jul;34(7):433-6. doi: 10.1002/clc.20910. Epub 2011 Jun 15. — View Citation
Disertori M, Masè M, Ravelli F. Myocardial fibrosis predicts ventricular tachyarrhythmias. Trends Cardiovasc Med. 2017 Jul;27(5):363-372. doi: 10.1016/j.tcm.2017.01.011. Epub 2017 Feb 2. Review. — View Citation
Dixon T, Lim LL, Oldridge NB. The MacNew heart disease health-related quality of life instrument: reference data for users. Qual Life Res. 2002 Mar;11(2):173-83. — View Citation
Farrington CP, Manning G. Test statistics and sample size formulae for comparative binomial trials with null hypothesis of non-zero risk difference or non-unity relative risk. Stat Med. 1990 Dec;9(12):1447-54. — View Citation
Felker GM, Thompson RE, Hare JM, Hruban RH, Clemetson DE, Howard DL, Baughman KL, Kasper EK. Underlying causes and long-term survival in patients with initially unexplained cardiomyopathy. N Engl J Med. 2000 Apr 13;342(15):1077-84. — View Citation
Gart JJ, Nam J. Approximate interval estimation of the ratio of binomial parameters: a review and corrections for skewness. Biometrics. 1988 Jun;44(2):323-38. Review. — View Citation
Gart JJ, Nam JM. Approximate interval estimation of the difference in binomial parameters: correction for skewness and extension to multiple tables. Biometrics. 1990 Sep;46(3):637-43. Erratum in: Biometrics 1992 Sep;48(3):979. — View Citation
Gulati A, Jabbour A, Ismail TF, Guha K, Khwaja J, Raza S, Morarji K, Brown TD, Ismail NA, Dweck MR, Di Pietro E, Roughton M, Wage R, Daryani Y, O'Hanlon R, Sheppard MN, Alpendurada F, Lyon AR, Cook SA, Cowie MR, Assomull RG, Pennell DJ, Prasad SK. Association of fibrosis with mortality and sudden cardiac death in patients with nonischemic dilated cardiomyopathy. JAMA. 2013 Mar 6;309(9):896-908. doi: 10.1001/jama.2013.1363. Erratum in: JAMA. 2013 Jul 3;310(1):99. — View Citation
Haugaa KH, Tilz R, Boveda S, Dobreanu D, Sciaraffia E, Mansourati J, Papiashvili G, Dagres N. Implantable cardioverter defibrillator use for primary prevention in ischaemic and non-ischaemic heart disease-indications in the post-DANISH trial era: results of the European Heart Rhythm Association survey. Europace. 2017 Apr 1;19(4):660-664. doi: 10.1093/europace/eux089. — View Citation
Hawkins NM, Grubisic M, Andrade JG, Huang F, Ding L, Gao M, Bashir J. Long-term complications, reoperations and survival following cardioverter-defibrillator implant. Heart. 2018 Feb;104(3):237-243. doi: 10.1136/heartjnl-2017-311638. Epub 2017 Jul 26. — View Citation
Kadish A, Dyer A, Daubert JP, Quigg R, Estes NA, Anderson KP, Calkins H, Hoch D, Goldberger J, Shalaby A, Sanders WE, Schaechter A, Levine JH; Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation (DEFINITE) Investigators. Prophylactic defibrillator implantation in patients with nonischemic dilated cardiomyopathy. N Engl J Med. 2004 May 20;350(21):2151-8. — View Citation
Køber L, Thune JJ, Nielsen JC, Haarbo J, Videbæk L, Korup E, Jensen G, Hildebrandt P, Steffensen FH, Bruun NE, Eiskjær H, Brandes A, Thøgersen AM, Gustafsson F, Egstrup K, Videbæk R, Hassager C, Svendsen JH, Høfsten DE, Torp-Pedersen C, Pehrson S; DANISH Investigators. Defibrillator Implantation in Patients with Nonischemic Systolic Heart Failure. N Engl J Med. 2016 Sep 29;375(13):1221-30. doi: 10.1056/NEJMoa1608029. Epub 2016 Aug 27. — View Citation
Kutyifa V, Geller L, Bogyi P, Zima E, Aktas MK, Ozcan EE, Becker D, Nagy VK, Kosztin A, Szilagyi S, Merkely B. Effect of cardiac resynchronization therapy with implantable cardioverter defibrillator versus cardiac resynchronization therapy with pacemaker on mortality in heart failure patients: results of a high-volume, single-centre experience. Eur J Heart Fail. 2014 Dec;16(12):1323-30. doi: 10.1002/ejhf.185. Epub 2014 Nov 7. — View Citation
Petrie MC, Connelly DT, Gardner RS. Who needs an implantable cardioverter-defibrillator? Controversies and opportunities after DANISH. Eur J Heart Fail. 2018 Mar;20(3):413-416. doi: 10.1002/ejhf.1135. Epub 2018 Jan 12. — View Citation
Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JG, Coats AJ, Falk V, González-Juanatey JR, Harjola VP, Jankowska EA, Jessup M, Linde C, Nihoyannopoulos P, Parissis JT, Pieske B, Riley JP, Rosano GM, Ruilope LM, Ruschitzka F, Rutten FH, van der Meer P; Authors/Task Force Members; Document Reviewers. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail. 2016 Aug;18(8):891-975. doi: 10.1002/ejhf.592. Epub 2016 May 20. — View Citation
Shen L, Jhund PS, Petrie MC, Claggett BL, Barlera S, Cleland JGF, Dargie HJ, Granger CB, Kjekshus J, Køber L, Latini R, Maggioni AP, Packer M, Pitt B, Solomon SD, Swedberg K, Tavazzi L, Wikstrand J, Zannad F, Zile MR, McMurray JJV. Declining Risk of Sudden Death in Heart Failure. N Engl J Med. 2017 Jul 6;377(1):41-51. doi: 10.1056/NEJMoa1609758. — View Citation
Stavrakis S, Asad Z, Reynolds D. Implantable Cardioverter Defibrillators for Primary Prevention of Mortality in Patients With Nonischemic Cardiomyopathy: A Meta-Analysis of Randomized Controlled Trials. J Cardiovasc Electrophysiol. 2017 Jun;28(6):659-665. doi: 10.1111/jce.13204. Epub 2017 Apr 18. — View Citation
Strickberger SA, Hummel JD, Bartlett TG, Frumin HI, Schuger CD, Beau SL, Bitar C, Morady F; AMIOVIRT Investigators. Amiodarone versus implantable cardioverter-defibrillator:randomized trial in patients with nonischemic dilated cardiomyopathy and asymptomatic nonsustained ventricular tachycardia--AMIOVIRT. J Am Coll Cardiol. 2003 May 21;41(10):1707-12. — View Citation
Ware JE Jr, Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care. 1992 Jun;30(6):473-83. — View Citation
* Note: There are 23 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Re-hospitalization for heart failure | Event rate | 0-3 years after device implantation | |
Primary | Ventricular tachycardia | Event rate, sustained ventricular tachycardia documentation during follow-up | 0-3 years after device implantation | |
Primary | Major adverse cardiac events (MACE) | Event rate of MACE, defined as a composite of nonfatal stroke, nonfatal myocardial infarction, and cardiovascular death | 0-3 years after device implantation | |
Secondary | Sudden cardiac death | Event rate of sudden cardiac death | 0-3 years after device implantation | |
Secondary | Cardiovascular death | Event rate of cardiovascular death | 0-3 years after device implantation | |
Secondary | Resuscitated cardiac arrest or sustained ventricular tachycardia | Event rate of resuscitated cardiac arrest or sustained ventricular tachycardia | 0-3 years after device implantation | |
Secondary | Device-related complications | Event rate of any complication requiring hospitalization | 0-3 years after device implantation | |
Secondary | The impact in terms of overall quality of life by the SF-36 Questionnaire | The SF-36 measures eight scales: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100. The lower the score the more disability. The higher the score the less disability. | 3 years after device implantation | |
Secondary | The impact in terms of overall quality of life by the MacNew Questionnaire | The MacNew consists of 27 items which fall into three domains: 13-item physical limitations domain scale, 14-item emotional function domain scale, 13-item social function domain scale. The maximum possible score in any domain is 7 (high QoL). The minimum is 1 (low QoL). Missing responses do not contribute to the score. | 3 years after device implantation |