Tailoring Pacemaker Output to Physiology in Chronic Heart Failure

NCT03781427 | Unknown Phase 3

• 1 other identifier: 258781
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

Aims: To explore the clinical effect on exercise tolerance and quality of life, safety and tolerability of pacing at higher outputs in patients with chronic heart failure and a pacemaker. Background: Heart failure (HF) is a very common condition of breathlessness or fatigue associated with heart muscle weakness. In around 30% of people with HF, a pacemaker-based treatment known as cardiac resynchronization therapy (CRT) can improve symptoms and prognosis by retuning the timing of the contraction of the heart. However, the effect of CRT is variable and unpredictable, with around 1 in 3 of people obtaining no obvious symptomatic benefit. One of the reasons for this might be that the pacemaker pulse does not activate all of the heart muscle cells at the same time or at all. In order to provide the longest possible battery life span, the default programming for all pacemakers is to provide a stimulus at an arbitrary level above the capture threshold (at which the spike leads to contraction). Whilst this is reasonable in a normal heart where the aim is to treat a slow heart rate, in heart failure, where the aim is to retune all parts of the heart, it is possible that this is not enough to provide consistent contraction of all heart muscle cells. It is possible that providing a higher output electrical signal from the pacemaker will activate more of the heart muscle cells immediately and thereby improve the contraction of the heart. The investigators think that this might be important at rest, but even more important during activity. This concept has never been tested before in a systematic manner but could have large implications for people with heart failure and existing CRT devices which could simply be reprogrammed to derive greater benefits for patients during everyday activities. Design: The proposed project has two parts: Study 1 - 105 patients with a CRT pacemaker for heart failure but ongoing symptoms will be invited to attend the National Institute of Health Research Clinical Research Facility. Symptoms, medication, hospitalisation information will be collected and a heart ultrasound scan using the pacemaker to increase the heart rate will be done to describe the force frequency relationship. Patients will perform a cardiopulmonary exercise test. Of these patients, 40 will be invited to return for two further visits, to perform an exercise test each time with the pacemaker programmed to its usual output or high output pacing. At each visit, including the heart scans, the order of the programming will be random, and neither the observer nor the patient will know how the device has been programmed. Study 2 - 70 patients will be invited to participate in a longer term study of whether high output pacing is safe, well tolerated and has effects on walk time (on a treadmill) and heart pumping function. Participants will be randomly allocated to one of two groups: high output or standard pacemaker settings. In the high output group, the pacemaker will be programmed to deliver the highest output possible or tolerated. In the standard care group patients will have standard output settings.

Conditions

Chronic Heart Failure

Keywords

Pacemaker; Cardiac resynchronization therapy

Outcome Measures

Primary Outcomes (1)

• Change in treadmill based exercise time

  Time (seconds)

  6 months

Secondary Outcomes (5)

• Quality of life

  6 Months

• Modified Packer score

  6 months

• Left ventricular end diastolic and end systolic diameter

  6 months

• Left ventricular end diastolic and end systolic volumes

  6 months

• Left ventricular ejection fraction

  6 months

Study Arms (2)

Standard care

ACTIVE COMPARATOR

Cardiac resynchronization therapy: Usual output programming

Device: Cardiac resynchronization therapy

High output

EXPERIMENTAL

Cardiac resynchronization therapy: High output programming

Device: Cardiac resynchronization therapy

Interventions

Cardiac resynchronization therapy DEVICE

Left ventricular pacing

High output; Standard care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Symptomatic heart failure due to left ventricular systolic dysfunction (LVEF\<50%)
• Willing and able to give informed consent
• CRT-D or CRT-P device in situ (\>6 months)

You may not qualify if:

• Angina pectoris symptoms limiting exercise tolerance
• Unstable heart failure symptoms (medical therapy changes in last three months)
• Poor imaging quality (details of patients excluded for this reason will be recorded)
• Calcium channel blocker use (these depress the force of contraction at all heart rates)
• Uncontrolled heart rate (either atrial fibrillation or sinus rhythm (\>80bts/min))
• Co-morbidities significantly affecting exercise or symptoms such as severe chronic airways disease or arthritis
• Haemodynamically significant aortic stenosis

Sponsors & Collaborators

• University of Leeds: lead

Study Sites (1)

Leeds General Infirmary

Leeds, United Kingdom

RECRUITING

MeSH Terms

Interventions

Cardiac Resynchronization Therapy

Intervention Hierarchy (Ancestors)

Cardiac Pacing, Artificial; Electric Stimulation Therapy; Therapeutics

Study Officials

• Klaus K Witte

  University of Leeds

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Klaus K Witte, MD

CONTACT

+447768254073; k.k.witte@leeds.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Lecturer in Cardiology

Study Record Dates

• First Submitted: December 18, 2018
• First Posted: December 19, 2018
• Study Start: February 1, 2020
• Primary Completion: July 1, 2023
• Study Completion: August 1, 2023
• Last Updated: November 2, 2022

Record last verified: 2022-10

Locations

GB (1)