Heart Rate Controller in Computed Tomography Coronary Angiography

May 15, 2022 updated by: Mahidol University

Heart Rate Controller in Computed Tomography Coronary Angiography: A Randomized Controlled Trial of Metoprolol, Diltiazem and Ivabradine

Coronary computed tomography angiography (CCTA) is one of important non-invasive test for diagnosis of coronary artery disease. Cardiac motion artifact by heart rate (HR) has impact on CCTA interpretation. Current recommendation suggests HR reduction at less than 60 bpm with using of oral metoprolol. However, there are populations that are contraindicated for beta blockers. There were scantly data of calcium channel blocker and ivabradine. Moreover, there is no data comparing these 3 drug groups within single trial This double-blinded randomized controlled trial compares oral metoprolol immediate release, diltiazem immediate release and ivabradine with primary endpoint of patients' percentage to achieve target HR lower than 60 bpm prior to CCTA.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Coronary computed tomography angiography (CCTA) is one of important non-invasive test for diagnosis coronary artery disease. Information of CCTA can provide information such as coronary artery lumen, vessel wall, degree of stenosis and component of coronary arterial plaque. Most of studies in CCTA represent high negative predictive value (NPV) approximately 93-100 %.However, motion artifact has impact on CCTA interpretation, especially when heart rate (HR) at more than 70 beat-per-minute (bpm). Therefore, HR reduction maneuver is necessary for CCTA. Current recommendation suggests HR reduction at < 60 bpm for best quality of CCTA imaging and to minimized duration of exposure to radiation using either beta blockers or non-dihydropyridine calcium channel blockers. According to North American Society for Cardiovascular Imaging (NASCI) recommendation in 2016, oral beta blocker prior to CCTA in patient with HR > 60 bpm is the preferred intervention. The recommended oral beta blocker usually is metoprolol 50-100 mg 1 hour prior to CCTA. The dosage of metoprolol must not exceed 400 mg/day. However, there are populations that are contraindicated or need to avoid beta blockers, such as uncontrolled obstructive airway disease, patient with baseline SBP < 100 mmHg, etc. Also, data in many clinical trials suggested that even high dose beta blockers can't controlled HR to target prior to CCTA in some patients. These pieces of information lead to alternative drugs to control HR prior to CCTA.

In previous clinical trials, the effective of non-dihydropyridine calcium channel blockers to control HR prior to CCTA compare to beta blockers had unclear results. In one study, Intravenous (IV) diltiazem is as effective in HR lowering to target to less than 60 bpm as IV metoprolol. Another study expressed inferior result of oral verapamil 1 hour before CCTA compared to oral metoprolol. However, there was heterogeneity in population of metoprolol and verapamil groups. According to FDA, immediate release (IR) diltiazem has onset of action faster than verapamil IR at 30 & 60-120 min., respectively. Initial dose of diltiazem in patients with chronic stable coronary artery disease and supraventricular tachycardia is at 30 - 60 mg oral every 6 hour and not exceed 360 mg/day.

Another agent that started to gain more evidence in HR control is ivabradine. Ivabradine has high selective and inhibitive property to If current channel which related to sinus node pace maker activity. Thus, other ion current channel normally doesn't get involved and doesn't have direct other cardiovascular effect. From meta-analysis, patients received ivabradine significantly achieving target HR to at least 65 bpm more than beta blockers group prior to CCTA (OR 5.02; 95% CI 3.16- 7.98, p < 0.00001, I 2 = 20%). In current recommendation, dosage of ivabradine shouldn't exceed 15 mg per day in patients with heart failure and chronic stable coronary artery disease. However, ivabradine has contraindication in patient with atrial fibrillation and/or sinus node disease, which require other agent to achieve target HR prior to CCTA. In current situation, there is no clinical trial to compare effect of beta blocker, non-dihydropyridine calcium channel blocker and Ivabradine in HR reduction to achieve target prior to CCTA.

The aim of this study is to compare percentage of patients achieving target HR < 60 bpm medication prior to CCTA by using oral beta blockers, non-dihydropyridine calcium channel blocker and ivabradine for HR lowering. Our study is double-blinded randomized controlled trial using Metoprolol immediate release as representative of beta blockers for controlled group, Diltiazem immediate release as representative of non-dihydropyridine calcium channel blocker and ivabradine. We blinded both investigators and patients using encapsulated drugs distribute from Siriraj's dispensary and randomly assign to our patients. The secondary objective of this study is to compare side effects, time to achieve target HR & CCTA image quality using 5 point grade scale and modified 15-segment American College of Cardiology and American Heart Association (AHA) between oral Metoprolol immediate, Diltiazem immediate release and ivabradine.

Study Type

Interventional

Enrollment (Anticipated)

246

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Thailand
    • Bangkoknoi
      • Bangkok, Bangkoknoi, Thailand, 10700
        • Recruiting
        • Department of Internal Medicine, Faculty of Medicine, Siriraj Hospital Mahidol University
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Age of at least 18 year-old
  2. Received Coronary CT angiography at Siriraj Hospital to evaluate diagnosis of coronary artery disease or risk stratification of coronary artery disease
  3. Normal sinus rhythm with baseline HR > 60 bpm which cardiac imaging specialist suggest using HR lowering intervention

Exclusion Criteria:

  1. Atrial fibrillation
  2. Previous pacemaker implantation
  3. II- and III-degree atrio-ventricular-block
  4. NHYA class III - IV
  5. Documented LVEF < 40%
  6. Contraindication for CCTA: Impaired renal function (serum creatinine > 1.5 mg/dl), known allergy to iodinated contrast media, pregnancy, thyroid disease
  7. Blood pressure < 100/70 mmHg
  8. Uncontrolled asthma and/or chronic obstructive pulmonary disease (defined as GOLD stage D) and/or uncontrolled reactive airway disease
  9. Current medication which cause severe interaction with calcium channel blocker, beta blocker and/or Ivabradine
  10. Known allergy to calcium channel blocker, beta blocker and/or Ivabradine

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Factorial Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Metoprolol protocol
  1. Metoprolol tartrate 50 mg will be given if patient's HR is more than 60 bpm.
  2. Monitor BP and heart rate HR every 15 minute to assess targeted HR and side effects until patient's is sent to CCTA.
  3. If patient can not reach targeted HR (less than 60 bpm) at 30 minutes, then second dose of 50-mg metoprolol will be given.
  4. If patient can not reach targeted HR at next 30 minutes, then third dose of 50-mg metoprolol will be given.
  5. If patient can not reach targeted HR at next 30 minutes, then fourth dose of 50-mg metoprolol will be given.
  6. If patient's HR reach targeted HR for 15 minutes apart for 2 times or received total dose of 200 mg metoprolol tartrate, then total time will be recorded and patient will proceed to CCTA.
  7. If patient can not reach targeted HR according to protocol, cardiac imaging specialist will decide whether to give further medication for HR control or proceed to CCTA. Cardiac imaging specialist may be able to consult dispensary.
Drug: Metoprolol tartrate
Prescribe oral metoprolol tartrate according to doses and time duration until patient reach targeted HR of less than 60 bpm or maximize dose according to each drug protocols prior to CCTA.
Experimental: Ivabradine protocol
  1. Ivabradine 5 mg will be given if patient's HR is more than 60 bpm.
  2. Monitor BP and heart rate HR every 15 minute to assess targeted HR and side effects until patient's is sent to CCTA.
  3. If patient can not reach targeted HR (less than 60 bpm) at 30 minutes, then second dose of 5-mg Ivabradine will be given.
  4. If patient can not reach targeted HR at next 30 minutes, then third dose of 5-mg Ivabradine will be given.
  5. If patient can not reach targeted HR at next 30 minutes, then placebo will be given.
  6. If patient's HR reach targeted HR for 15 minutes apart for 2 times or received total dose of 15 mg ivabradine with 1 dose of placebo, then total time will be recorded and patient will proceed to CCTA.
  7. If patient can not reach targeted HR according to protocol, cardiac imaging specialist will decide whether to give further medication for HR control or proceed to CCTA. Cardiac imaging specialist may be able to consult dispensary.
Drug: Ivabradine
Prescribe oral ivabradine according to doses and time duration until patient reach targeted HR of less than 60 bpm or maximize dose according to each drug protocols prior to CCTA.
Experimental: Diltiazem protocol
  1. Diltiazem immediate release (IR) 30 mg will be given if patient's HR is more than 60 bpm.
  2. Monitor BP and heart rate HR every 15 minute to assess targeted HR and side effects until patient's is sent to CCTA.
  3. If patient can not reach targeted HR (less than 60 bpm) at 30 minutes, then second dose of 30-mg diltiazem will be given.
  4. If patient can not reach targeted HR at next 30 minutes, then third dose of 30-mg diltiazem will be given.
  5. If patient can not reach targeted HR at next 30 minutes, then fourth dose of 30-mg diltiazem will be given.
  6. If patient's HR reach targeted HR for 15 minutes apart for 2 times or received total dose of 120 mg 30-mg diltiazem IR, then total time will be recorded and patient will proceed to CCTA.
  7. If patient can not reach targeted HR according to protocol, cardiac imaging specialist will decide whether to give further medication for HR control or proceed to CCTA. Cardiac imaging specialist may be able to consult dispensary.
Drug: Diltiazem
Prescribe oral diltiazem immediate-release according to doses and time duration until patient reach targeted HR of less than 60 bpm or maximize dose according to each drug protocols prior to CCTA.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percent of patient achieving target heart rate (HR)
Time Frame: 3 hours
To compare percentage of patient in achieving adequate HR control (defined as target HR of 60 bpm) among oral Ivabradine, metoprolol and diltiazem during CCTA
3 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Side effects
Time Frame: 3 hours
To compare side effects between oral Ivabradine, metoprolol and diltiazem during CCTA
3 hours
Time to achieve target HR
Time Frame: 3 hours
To compare time to achieve target HR of less than 60 bpm
3 hours
Image quality
Time Frame: 1 week
To compare image quality using 5 point grade scale and modified 15-segment American College of Cardiology and American Heart Association (AHA)
1 week

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Mahidol University

Investigators

  • Principal Investigator: Prichapol Thantassanee, M.D., Department of Internal Medicine, Faculty of Medicine, Siriraj Hospital Mahidol University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 30, 2021

Primary Completion (Anticipated)

June 20, 2022

Study Completion (Anticipated)

June 30, 2022

Study Registration Dates

First Submitted

February 6, 2022

First Submitted That Met QC Criteria

February 28, 2022

First Posted (Actual)

March 2, 2022

Study Record Updates

Last Update Posted (Actual)

May 17, 2022

Last Update Submitted That Met QC Criteria

May 15, 2022

Last Verified

May 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Si047/2021

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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