Pilot Study to Investigate the Creation of Physiological Rhythm by Closed Loop Stimulation in hEart Failure pAtients With chronoTropic incompEtence (BIO|CREATE)

BIO|CREATE Pilot Study

The study assesses the effect of Closed Loop Stimulation (CLS) on the ventilatory efficiency slope and estimates the patient responder rate to CLS in patients with severe chronotropic incompetence treated with a cardiac resynchronization therapy (CRT) device.

Study Overview

• Status: Completed
• Conditions: Heart Failure; CPX
• Intervention / Treatment: Device: Cardiac Resynchronization therapy device with Closed Loop Stimulation (CLS)

Detailed Description

In patients with pharmacological refractory heart failure (HF), systolic dysfunction, and cardiac dyssynchrony, the cardiac resynchronization therapy (CRT) reduces the risk of death, and improves symptoms and quality of life.

A considerable portion (80%) of patients with a CRT indication has a chronotropic incompetence (CI). CI usually induces a stress intolerance which negatively affects the quality of life. In addition of being a marker of diminished exercise capacity, severe CI (sCI) may be an independent predictor of mortality.

The sensor-based rate adaption provided by the implanted CRT device delivers a possible therapeutic approach for the CI.

Usually, rate adaption is achieved by an accelerometer. The previous studies in terms of effectiveness of rate adaption in CRT patients with CI showed inconsistent results.

In addition to an accelerometer to deliver the rate adaption BIOTRONIK provides closed loop stimulation (CLS) as unique feature in a CRT device. CLS determines the appropriate heart rate based on intra-cardiac impedance measurements. These measurements reflect changes of the cardiac contraction dynamics in reaction to information coming from the autonomic nervous system. CLS takes the information on the contraction dynamics and translates it into an adequate heart rate adaptation, thus delivering physiologically appropriate therapy.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany
    • Charité Universitätsklinikum - Campus Benjamin Franklin

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:

• CRT class I indication at time of implantation, according to current guidelines
• Implantation of CRT-device including CLS > 6 months prior to enrollment
• Stable heart failure status for at least 1 month
• Optimal cardiovascular drug treatment according to current guidelines
• NYHA class II or III
• Patient is able to comply with the protocol
• Patient provided written informed consent
• Stable location of residence

Exclusion Criteria:

• Planned cardiovascular intervention within the next 3 months
• Admission for decompensated heart failure or acute coronary syndrome in the preceding 3 months
• Ongoing symptoms of myocardial ischemia
• Known persistent, long-standing persistent or permanent atrial fibrillation
• COPD with GOLD ≥ 3
• Planned absence of residence for more than one week during study period
• Pregnant or breast-feeding women
• Participation in another interventional clinical investigation
• Age < 18 years
• Placed in an institution due to official decree or judicial order
• Dependent from the sponsor, the clinical site or the investigators

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Pacing mode with CLS	Device: Cardiac Resynchronization therapy device with Closed Loop Stimulation (CLS); The feature CLS will be programmed ON or Off according to a randomization list after one month after baseline visit. One month later the alternate will be programmed.; Other Names: Cardiac Resynchronization therapy device without Closed Loop Stimulation (CLS)
ACTIVE_COMPARATOR: Intrinsic mode	Device: Cardiac Resynchronization therapy device with Closed Loop Stimulation (CLS); The feature CLS will be programmed ON or Off according to a randomization list after one month after baseline visit. One month later the alternate will be programmed.; Other Names: Cardiac Resynchronization therapy device without Closed Loop Stimulation (CLS)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ventilatory efficiency slope	The slope of VE/VCO2 describes the ventilatory efficiency during effort, showing the amount of air that must be ventilated to eliminate 1 litre of CO2.	2 months

Collaborators and Investigators

• Sponsor: Biotronik SE & Co. KG
• Investigators: Principal Investigator: Mattias Roser, Dr., Charité Universitätsklinikum - Campus Benjamin Franklin

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 19, 2017
• Primary Completion (ACTUAL): March 31, 2019
• Study Completion (ACTUAL): April 30, 2019

Study Registration Dates

• First Submitted: May 16, 2017
• First Submitted That Met QC Criteria: May 16, 2017
• First Posted (ACTUAL): May 17, 2017

Study Record Updates

• Last Update Posted (ACTUAL): May 24, 2019
• Last Update Submitted That Met QC Criteria: May 23, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: CR019

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No