The Impact of Heart Rate on Central Blood Pressure in Sick Sinus Syndrome Patients With a Permanent Cardiac Pacemaker

• ClinicalTrials.gov Identifier: NCT03245996
• Recruitment Status: Completed
• First Posted: August 10, 2017
• Last Update Posted: July 10, 2018
• Sponsor: Tartu University Hospital
• Information provided by (Responsible Party): Tuuli Teeäär, Tartu University Hospital

Tracking Information

• First Submitted Date: August 8, 2017
• First Posted Date: August 10, 2017
• Last Update Posted Date: July 10, 2018
• Study Start Date: June 2015
• Actual Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 6, 2018)

• First part of the study: central systolic blood pressure [ Time Frame: 3 minutes after heart rate change ]
• Second part of the study: systolic blood pressure amplification [ Time Frame: 3 hours after drug administration and 3 minutes after heart rate change ]
  difference between peripheral and central systolic blood pressure

• Original Primary Outcome Measures (submitted: August 9, 2017): central systolic blood pressure [ Time Frame: 3 minutes after heart rate change ]
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: The Impact of Heart Rate on Central Blood Pressure in Sick Sinus Syndrome Patients With a Permanent Cardiac Pacemaker
• Official Title: The Impact of Heart Rate on Central Hemodynamics in Sick Sinus Syndrome Patients With a Permanent Cardiac Pacemaker

Brief Summary

This study is divided into two parts:

• The first part evaluates the acute effect of non-pharmacological heart rate change on central hemodynamic parameters noninvasively in sick sinus syndrome patients with a permanent cardiac pacemaker
• The second part evaluates the acute effects of atenolol, nebivolol and ivabradine on central hemodynamic parameters noninvasively in sick sinus syndrome patients with a permanent cardiac pacemaker at different pacing rate levels

Detailed Description

Patients with sick sinus syndrome and a double-chamber cardiac pacemaker are studied.

• To investigate the role of non-pharmacological heart rate change on central hemodynamics in the first part of the study, the investigators acutely change pacing rate from atrial paced-atrial sensed (AAI)-mode 60 to 40 to 90 bpm and obtain hemodynamic parameters noninvasively after a short stabilisation period after each pacemaker rate change.
• Subsequently, to investigate the acute effects of beta-blockers or ivabradine on central hemodynamics in the second part of the study, the investigators obtain central hemodynamic parameters noninvasively after acute administration of atenolol, nebivolol or ivabradine at the same pacing rate levels used in the first part of the study (AAI-mode 60, 40 and 90 bpm).

• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Intervention Model: Single Group Assignment; Masking: Single; Primary Purpose: Basic Science
• Condition: Aortic Blood Pressure

Intervention

• Device: AAI 40 bpm
  Cardiac pacemaker of the subjects is set to AAI-mode 40 bpm in the first and second part of the study
• Device: AAI 60 bpm
  Cardiac pacemaker of the subjects is set to AAI-mode 60 bpm in the first and second part of the study
• Device: AAI 90 bpm
  Cardiac pacemaker of the subjects is set to AAI-mode 90 bpm in the first and second part of the study
• Drug: Atenolol Pill
  50 or 100 mg of atenolol is administered to subjects in the second part of the study
• Drug: Nebivolol Pill
  5 mg of nebivolol is administered to subjects in the second part of the study
• Drug: Ivabradine Pill
  5 or 7,5 mg of ivabradine is administered to subjects in the second part of the study

Study Arms

Experimental: Subjects

Subjects with a cardiac pacemaker

Interventions:

• Device: AAI 40 bpm
• Device: AAI 60 bpm
• Device: AAI 90 bpm
• Drug: Atenolol Pill
• Drug: Nebivolol Pill
• Drug: Ivabradine Pill

• Publications *: Teeäär T, Serg M, Paapstel K, Kals J, Kals M, Zilmer M, Eha J, Kampus P. Heart rate reduction decreases central blood pressure in sick sinus syndrome patients with a permanent cardiac pacemaker. J Hum Hypertens. 2018 May;32(5):377-384. doi: 10.1038/s41371-018-0051-4. Epub 2018 Mar 27.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 9, 2017): 27
• Original Actual Enrollment: Same as current
• Actual Study Completion Date: September 2016
• Actual Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• age 18-75 years;
• dual-chamber pacemaker implanted due to sick sinus syndrome at least six months before; sinus rhythm

Exclusion Criteria:

• average seated office brachial systolic BP ≥160 mmHg and/or diastolic BP ≥ 100 mmHg; atrial pacing <40%;
• ventricular pacing >25%;
• unpaced QRS >120 ms and/or QTc >500 ms on 12-lead ECG;
• atrioventricular blockage at AAI-mode 90 bpm; resting HR >60 bpm at AAI-mode 40 bpm; irregular heart rate;
• automatic mode switching >10%;
• implantable cardioverter defibrillator or cardiac resynchronisation therapy pacemaker; treatment with digoxin, class Ic or III antiarrhythmic drugs;
• history of acute coronary syndrome;
• stable angina pectoris;
• heart failure with reduced left ventricular ejection fraction;
• history of cerebrovascular event;
• diabetes mellitus;
• chronic kidney disease with eGFR <30 ml/min/m2;
• peripheral artery disease;
• clinically relevant heart valve disease;
• active cancer;
• acute or chronic inflammatory disease;
• severe chronic respiratory or liver disease;
• pregnancy or breastfeeding
• contraindication or intolerance to atenolol, nebivolol, ivabradine or adjuvants

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Not Provided

Administrative Information

• NCT Number: NCT03245996
• Other Study ID Numbers: 14058
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: all data shared after completion of study as supplement to journal article

• Responsible Party: Tuuli Teeäär, Tartu University Hospital
• Study Sponsor: Tartu University Hospital
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Tartu University Hospital
• Verification Date: July 2018