Clinical trial NCT02454439: Assessment of Cardiac Resynchronization Therapy in Patients With Wide QRS and Non-specific Intraventricular Conduction Delay: a Randomized Trial
Official title: Assessment of Cardiac Resynchronization Therapy in Patients With Wide QRS and Non-specific Intraventricular Conduction Delay: a Randomized Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Heart Failure
Keywords: 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
Lead sponsor: University Hospital, Clermont-Ferrand
Sponsor class: OTHER
Collaborators: name: Boston Scientific Corporation
First posted: 2015-05-27
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

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 thirteen sites in France(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, Georges Pompidou European Hospital) and two sites in the Netherlands (Maastricht University Hospital and Radboud University Medical Center)

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)and comparison of the death and percentage of hospitalization in both group which is the primary endpoint.

Eligibility 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

Non inclusion criteria :

* Inability to understand nor decline the study,
* Impaired mobility,
* Unable to fill out questionnaire independently,
* Patients with permanent atrial fibrillation,
* Pregnant women,
* Dependant adult,
* Patients minor,
* Life expectancy \< 1 year due to other causes than HF.

Primary outcomes:
measure: Composite of 2 clinical endpoints combined (12 months all-cause deaths and percentage of hospitalizations for HF at 12 months) combined using an average z-score.
timeFrame: at 12 months
Secondary outcomes:
measure: Evaluation of efficacy, analysis of 12- month deaths
timeFrame: at 6 and 12 months
measure: Evaluation of efficacy, analysis of - Quality-of-life questionnaires
timeFrame: at 6 and 12 months
measure: Evaluation of efficacy, analysis of Functional capacity
timeFrame: at 6 and 12 months
measure: Evaluation of efficacy, analysis of Percentage of hospitalizations for HF
timeFrame: at 6 and 12 months
measure: Evaluation of efficacy, analysis of left ventricule volume by echocardiography transthoracic
timeFrame: at 6 and 12 months
measure: Evaluation of efficacy, Packer score
timeFrame: at 6 and 12 months
Other outcomes:
Locations:
city: Clermont-Ferrand
country: France
facility: CHU Clermont-Ferrand
Study officials:
affiliation: University Hospital, Clermont-Ferrand
name: Romain ESCHALIER
role: PRINCIPAL_INVESTIGATOR
References:
citation: Eschalier R, Ploux S, Pereira B, Clementy 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.