Right Ventricular Resynchronization Therapy (RVRT)

Long-term Right Ventricular Resynchronization Therapy for Chronic Thromboembolic Pulmonary Hypertension

The purpose of this study is to determine whether cardiac resynchronization therapy with the use of an implanted electronic pacemaker reduces morbidity associated with chronic thromboembolic pulmonary hypertension

Study Overview

• Status: Unknown
• Conditions: Pulmonary Hypertension; Chronic Thromboembolic Pulmonary Hypertension; Right Ventricular Failure
• Intervention / Treatment: Device: Implantation of 3-chamber pacemaker

Detailed Description

Rationale: The clinical severity of right ventricular disease is largely determined by right-to-left ventricular dyssynchrony, i.e., delay of electrical activity between the right and left ventricles. Moreover, in patients with chronic thromboembolic pulmonary hypertension (CTEPH), we found that acute correction of this dyssynchrony by temporary pacing (prior to pulmonary endarterectomy, presently the therapy of choice for CTEPH) results in significant improvement in cardiac output. In this study, we aim to establish whether chronic pacing with the use of implanted pacemakers confers long-lasting improvements in cardiac output and functional class.

Objective: To study whether chronic pacing with implanted pacemakers confers long-lasting improvements in cardiac output and functional class in severely symptomatic CTEPH patients who are not eligible for pulmonary endarterectomy, or those in whom pulmonary endarterectomy has failed.

Study design: Chronic intervention study, double-blinded, randomized, cross-over.

Study population: Adult CTEPH patients who are not eligible for pulmonary endarterectomy, or those in whom pulmonary endarterectomy has failed.

Intervention (if applicable): chronic right ventricular resynchronization therapy (RVRT), i.e., chronic right atrial, right ventricular, and left ventricular pacing with the use of implanted pacemakers.

Main study parameters/endpoints: (Duration of) improvements (in l/min) in cardiac output as measured using Doppler echocardiography, and functional class as measured using 6-minute walking distance (6-MWD), right and left ventricular dimensions and ejection fractions (99mTechnetium scintigraphy), biomarkers for heart failure (serum NT-proBNP levels), and quality of life (SF-36) questionnaire.

Design: Randomized, double-blind, cross-over study with 2 arms of 10 patients each (arms 1 and 2). In arm 1, RVRT is switched on immediately after pacemaker implant, is switched of in week 5, and switched on at the start of week 6 until study end (32 weeks). In arm 2, RVRT is switched at the start of week 5 after pacemaker implant until study end (32 weeks). At various follow-up visits at weeks 1, 4, 5, 6, 8, 12, 16, the main study parameters/endpoints (see previous paragraph) will be assessed.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Academic Medical Center, University of Amsterdam

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Adult patients with chronic thromboembolic pulmonary hypertension (CTEPH) who are ineligible for pulmonary endarterectomy, and those in whom pulmonary endarterectomy has failed

Exclusion Criteria:

None

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Immediate RVRT; RVRT switched on immediately after pacemaker implant	Device: Implantation of 3-chamber pacemaker; Implantation of pacemaker with leads in right atrium, right ventricle, and coronary sinus (left ventricle) with the aim of providing right ventricular resynchronization therapy (RVRT); this is accomplished by pacing the right ventricle ahead of the left ventricle, e.g., by setting (shortening) the A-V delay between right atrium and right ventricle to an optimal level.; Other Names: Medtronic CRT pacemaker systems will be implanted
Placebo Comparator: Delayed RVRT; RVRT switched on 4 weeks after pacemaker implant	Device: Implantation of 3-chamber pacemaker; Implantation of pacemaker with leads in right atrium, right ventricle, and coronary sinus (left ventricle) with the aim of providing right ventricular resynchronization therapy (RVRT); this is accomplished by pacing the right ventricle ahead of the left ventricle, e.g., by setting (shortening) the A-V delay between right atrium and right ventricle to an optimal level.; Other Names: Medtronic CRT pacemaker systems will be implanted

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Improvement in right/left ventricular synchrony measured using tissue Doppler echocardiography	within 8 months after pacemaker implantation
Increase in cardiac output measured using Doppler echocardiography and scintigraphy	within 8 months after pacemaker implantation
Increase in functional capacity measured with six-minute walking distance	within 8 months after pacemaker implantation

Secondary Outcome Measures

Outcome Measure	Time Frame
Increase in well-being assessed with questionnaire	within 8 months after pacemaker implantation

Collaborators and Investigators

• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Collaborators: Medtronic
• Investigators: Principal Investigator: Hanno L Tan, MD,PhD, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Study record dates

Study Major Dates

• Study Start: July 1, 2010
• Primary Completion (Anticipated): July 1, 2012
• Study Completion (Anticipated): July 1, 2012

Study Registration Dates

• First Submitted: July 14, 2010
• First Submitted That Met QC Criteria: July 14, 2010
• First Posted (Estimate): July 15, 2010

Study Record Updates

• Last Update Posted (Estimate): July 15, 2010
• Last Update Submitted That Met QC Criteria: July 14, 2010
• Last Verified: December 1, 2009

More Information

Terms related to this study

• Keywords: Pulmonary hypertension; Cardiac resynchronization therapy; Pacemaker; Right ventricular failure
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension; Hypertension, Pulmonary
• Other Study ID Numbers: MEC 09/307