Assessment of Cardiac Resynchronization Therapy in Patients With Wide QRS and Non-specific Intraventricular Conduction Delay: a Randomized Trial

• Sponsor: University Hospital, Clermont-Ferrand
• Collaborator: Boston Scientific Corporation
• Information provided by (Responsible Party): University Hospital, Clermont-Ferrand

Study Description

Brief Summary:

The aim of the NICD-CRT study is to assess whether CRT may be clinically beneficial in HF patients with NICD and reduced ejection fraction on 12-month HF status.

In effect, the effectiveness of cardiac resynchronization therapy in heart failure (HF) with reduced ejection fraction patients with non specific intraventricular conduction delay (NICD) has never been confirmed even if it is recommended.

At the moment, no dedicated study has already been performed to assess the benefit of CRT in patients with NICD. Results from CRT therapy are contradictory in this patient group and have only been obtained from subgroup analysis. Some of them don't show clinical benefit but others show a benefit in term of an end-diastolic and/or end-systolic left ventricular volume (decrease of the size and the volumes of left ventricule).

The AHA/ACCF guidelines, published in 2005 and updated in 2009, considered only QRS duration (≥120 ms) for the indication of CRT implantation, without any consideration for the type of conduction disorder (i.e. LBBB vs. non-LBBB), current updated 2012 ACCF/AHA/HRS guidelines, consider QRS morphology (i.e. LBBB) as the first step for CRT candidate selection in addition to QRS duration (>150 ms). Indications for resynchronization have been restricted since indication of CRT in non-LBBB patients (e.g. NICD) is only a class IIa (>150 ms, only in NYHA III and ambulatory IV; level of evidence A). The same modifications have been applied between 2011 and 2013 in the European guidelines. None is known about patients with NICD and QRS > 130 ms.

Condition or disease	Intervention/treatment	Phase
Heart Failure	Other: CRT implantation	Phase 4

Detailed Description:

This is a pilot, prospective, controlled, two-parallel arm, randomized, double-blind design and multicentric clinical trial comparing a CRT-D or CRT-P ON group vs. CRT-D or CRT-P OFF group in HF with reduced ejection fraction patients with NICD.

Patients will be included in twelve French centers (Clermont-Ferrand University Hospital, Côte Basque Hospital, Bordeaux University Hospital, Saint-Augustin Clinic, Limoges University Hospital, Grenoble University Hospital, Nantes University Hospital, Nantes New Clinic, Rennes University Hospital, Saint-Etienne University Hospital, Tours University Hospital, Toulouse University Hospital).

1. At baseline a preimplantation evaluation is performed: clinical examination, ECG, six minute walk test, biology analysis, quality of life assessment, echocardiography, peak oxygen consumption.

2. At 6 months, evaluation of efficacy which is the secondary assessment criteria:

   • Quality of life: Minnesota Living With Heart Failure Questionnary: MLWHFQ) : improvement of at least 20 points
   • Functionnal capacity :

   NYHA classification reduction ≥ 1 class, 6-minute walk test improvement of at least 10 % in distance, Peak oxygen consumption increased by 1.0 ml/kg/minNYHA response to CRT is the primary endpoint. It is a composite primary endpoint, including modification of: Quality of Life Score (MINNESOTA scale), NYHA functional status , 6-minute walk test and volume of the left ventricle.

   - Percentage of hospitalizations for HF, for cardiovascular reasons and for all causes Decrease >15% in end-diastolic and/or end-systolic volumes of the left ventricle.

3. At 12 months, comparison of the proportion of improved, unchanged and worsend patients (Packer Score) in both group which is the primary endpoint and new evaluation of the CRT efficacy (same as 6 months)

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	200 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Double (Participant, Investigator)
Official Title:	Assessment of Cardiac Resynchronization Therapy in Patients With Wide QRS and Non-specific Intraventricular Conduction Delay: a Randomized Trial
Study Start Date :	May 2015
Estimated Primary Completion Date :	May 2018
Estimated Study Completion Date :	November 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: CRT-D or CRT-P ON; This is a pilot, prospective, controlled, two-parallel arm, randomized, double-blind design and multicentric clinical trial comparing a CRT-D or CRT-P ON group vs. CRT-D or CRT-P OFF group in HF with reduced ejection fraction patients with NICD.	Other: CRT implantation
CRT-D or CRT-P OFF; This is a pilot, prospective, controlled, two-parallel arm, randomized, double-blind design and multicentric clinical trial comparing a CRT-D or CRT-P ON group vs. CRT-D or CRT-P OFF group in HF with reduced ejection fraction patients with NICD.	Other: CRT implantation

Outcome Measures

Primary Outcome Measures :

1. proportion of improved, unchanged and worsened patients in both groups. [ Time Frame: at 12 months ]

   According to composite Packer classification:

   • Patients are considered improved if at the final visit they experienced a favorable change in NYHA functional class or in the patient global assessment (or both) of a prespecified magnitude but did not experience any major adverse clinical events during the course of the trial.
   • Patients are considered worse if they experienced a major clinical event during the planned duration of double-blind treatment or reported worsening of their NYHA class or global assessment at the final visit.

   Patients are considered unchanged if they are neither improved nor worse.

Secondary Outcome Measures :

1. Evaluation of efficacy, analysis of 12- month deaths [ Time Frame: at 6 and 12 months ]
   HF, cardiovascular and all causes deaths
2. Evaluation of efficacy, analysis of - Quality-of-life questionnaires [ Time Frame: at 6 and 12 months ]
   Minnesota Living With Heart Failure Questionnaire: MLWHFQ): improvement of at least 20 points
3. Evaluation of efficacy, analysis of Functional capacity [ Time Frame: at 6 and 12 months ]
   NYHA classification reduction ≥ 1 class, 6-minute walk test improvement of at least 10 % in distance, Peak oxygen consumption increased by 1.0 ml/kg/min
4. Evaluation of efficacy, analysis of Percentage of hospitalizations for HF [ Time Frame: at 6 and 12 months ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• Patients over 18 years' old
• NYHA class II to IV ambulatory
• QRS duration > 130 ms
• Patients with sinus rhythm
• LVEF < 35%
• QRS morphology: NICD according to the AHA/ACCF/HRS Recommendations (non-LBBB and non-RBBB):
• Not broad notched or slurred R wave in leads I, aVL, V5 and V6;
• Presence of a Q wave in leads I, V5, V6;
• No rsr', rsR' or rSR' pattern in leads V1 or V2.
• Life expectancy expected to exceed one year with a good functional status
• Optimal pharmacological therapy of heart failure according to clinician

Exclusion Criteria:

Contacts and Locations

Contacts

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Contact: Patrick LACARIN	04 73 75 11 95	placarin@chu-clermontferrand.fr

Locations

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France
CHU Clermont-Ferrand	Recruiting
Clermont-Ferrand, France, 63003
Contact: Patrick LACARIN 04 73 75 11 95 placarin@chu-clermontferrand.fr
Principal Investigator: Romain ESCHALIER

Sponsors and Collaborators

University Hospital, Clermont-Ferrand

Boston Scientific Corporation

Investigators

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Principal Investigator:	Romain ESCHALIER	University Hospital, Clermont-Ferrand

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Eschalier R, Ploux S, Pereira B, Clémenty N, Da Costa A, Defaye P, Garrigue S, Gourraud JB, Gras D, Guy-Moyat B, Leclercq C, Mondoly P, Bordachar P. Assessment of cardiac resynchronisation therapy in patients with wide QRS and non-specific intraventricular conduction delay: rationale and design of the multicentre randomised NICD-CRT study. BMJ Open. 2016 Nov 11;6(11):e012383. doi: 10.1136/bmjopen-2016-012383.

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Responsible Party:	University Hospital, Clermont-Ferrand
ClinicalTrials.gov Identifier:	NCT02454439 History of Changes
Other Study ID Numbers:	CHU-0233; 2014-A01848-39 ( Registry Identifier: 2014-A01848-39 )
First Posted:	May 27, 2015
Last Update Posted:	September 22, 2015
Last Verified:	September 2015

Keywords provided by University Hospital, Clermont-Ferrand:

Heart Failure with reduced ejection fraction (<35%); Cardiac Resynchronisation Therapy; Non specific intraventricular conduction; Efficacy	Life expectancy expected to exceed one year with a good functional status; QRS morphology : NICD according to the AHA/ACCF/HRS Recommendations (non-LBBB and non-RBBB): QRS duration > 130 ms

Additional relevant MeSH terms:

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Heart Failure; Heart Diseases; Cardiovascular Diseases