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Heart RatePhase 4NCT05261464

Heart Rate Controller in Computed Tomography Coronary Angiography

A Phase 4 study testing Metoprolol tartrate, Ivabradine and Diltiazem in people with Heart Rate and Coronary Computed Tomography Angiography, run by Mahidol University at 1 site in Thailand.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Metoprolol tartrate, Ivabradine and Diltiazem
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
246 participants
Where
1 siteThailand
Study dates
30 Jan 2021to 30 Jun 2022
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

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

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

Prichapol Thantassanee, M.D. contact

+66896754200

char_uc0093@hotmail.com

Thananya Boonyasirinant, M.D. contact

+66860173767

drthananyaa@yahoo.com

Thailand1 site, 1 recruiting

  • Department of Internal Medicine, Faculty of Medicine, Siriraj Hospital Mahidol University

    Bangkok, Bangkoknoi, 10700

    Prichapol Thantassanee, M.D., +66896754200, char_uc0093@hotmail.com

    Thananya Boonyasirinant, M.D., +66860173767, drthananyaa@yahoo.com

    Recruiting

Other trials in Thailand

About this study

Official title: 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.

Read the 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.

Being tested
Metoprolol tartrate, Ivabradine, Diltiazem
Keywords
coronary computed tomography angiography (CCTA), Target Heart rate

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Metoprolol tartrateDrug

    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.

  • IvabradineDrug

    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.

  • DiltiazemDrug

    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.

Study groups in NCT05261464
Study groupRoleWhat they receive
Metoprolol protocolActive comparator1. 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.
Receives: Drug: Metoprolol tartrate
Ivabradine protocolExperimental1. 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.
Receives: Drug: Ivabradine
Diltiazem protocolExperimental1. 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.
Receives: Drug: Diltiazem

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percent of patient achieving target heart rate (HR)

    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

    Measured: 3 hours

Secondary outcomes (3)

  1. Side effects

    To compare side effects between oral Ivabradine, metoprolol and diltiazem during CCTA

    Measured: 3 hours

  2. Time to achieve target HR

    To compare time to achieve target HR of less than 60 bpm

    Measured: 3 hours

  3. Image quality

    To compare image quality using 5 point grade scale and modified 15-segment American College of Cardiology and American Heart Association (AHA)

    Measured: 1 week

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Mar 2022
  2. Study start30 Jan 2021
  3. Primary completion20 Jun 2022 (estimated)
  4. Study completion30 Jun 2022 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Factorial
Model description
1. Extract patients who undergo routine Computed Tomography Coronary Angiography (CCTA) with heart rate (HR) \> 60 bpm at rest 2. Enroll patients using Inform consent from the first date of study period until reach the required sample size 3. Randomize patients to 1:1:1 using 6 block randomization by nQuery program 4. Assign sequential encapsulated drugs distribute from Siriraj's dispensary to patients according to randomization and protocol prior to CCTA. 5. Assigned encapsulated until patient reaches target HR or until full dose according to each drugs protocol prior to CCTA. 6. Continuous monitor blood pressure and heart rate every 15 minutes and closed observe side effects and complication until at least 1 hr after finish CCTA. 7. Review medical record and CCTA results, then fill in case record forms.
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
246 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05261464
Sponsor's protocol ID
Si047/2021
Status last verified
May 2022
First submitted
6 Feb 2022
Last updated
17 May 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Budoff MJ, Dowe D, Jollis JG, Gitter M, Sutherland J, Halamert E, Scherer M, Bellinger R, Martin A, Benton R, Delago A, Min JK. Diagnostic performance of 64-multidetector row coronary computed tomographic angiography for evaluation of coronary artery stenosis in individuals without known coronary artery disease: results from the prospective multicenter ACCURACY (Assessment by Coronary Computed Tomographic Angiography of Individuals Undergoing Invasive Coronary Angiography) trial. J Am Coll Cardiol. 2008 Nov 18;52(21):1724-32. doi: 10.1016/j.jacc.2008.07.031.

    PubMed 19007693

  • Mollet NR, Cademartiri F, van Mieghem CA, Runza G, McFadden EP, Baks T, Serruys PW, Krestin GP, de Feyter PJ. High-resolution spiral computed tomography coronary angiography in patients referred for diagnostic conventional coronary angiography. Circulation. 2005 Oct 11;112(15):2318-23. doi: 10.1161/CIRCULATIONAHA.105.533471. Epub 2005 Oct 3.

    PubMed 16203914

  • Raff GL, Gallagher MJ, O'Neill WW, Goldstein JA. Diagnostic accuracy of noninvasive coronary angiography using 64-slice spiral computed tomography. J Am Coll Cardiol. 2005 Aug 2;46(3):552-7. doi: 10.1016/j.jacc.2005.05.056.

    PubMed 16053973

  • Pugliese F, Mollet NR, Runza G, van Mieghem C, Meijboom WB, Malagutti P, Baks T, Krestin GP, deFeyter PJ, Cademartiri F. Diagnostic accuracy of non-invasive 64-slice CT coronary angiography in patients with stable angina pectoris. Eur Radiol. 2006 Mar;16(3):575-82. doi: 10.1007/s00330-005-0041-0. Epub 2005 Nov 16.

    PubMed 16292649

  • Giesler T, Baum U, Ropers D, Ulzheimer S, Wenkel E, Mennicke M, Bautz W, Kalender WA, Daniel WG, Achenbach S. Noninvasive visualization of coronary arteries using contrast-enhanced multidetector CT: influence of heart rate on image quality and stenosis detection. AJR Am J Roentgenol. 2002 Oct;179(4):911-6. doi: 10.2214/ajr.179.4.1790911.

    PubMed 12239036

  • Abbara S, Arbab-Zadeh A, Callister TQ, Desai MY, Mamuya W, Thomson L, Weigold WG. SCCT guidelines for performance of coronary computed tomographic angiography: a report of the Society of Cardiovascular Computed Tomography Guidelines Committee. J Cardiovasc Comput Tomogr. 2009 May-Jun;3(3):190-204. doi: 10.1016/j.jcct.2009.03.004. Epub 2009 Mar 31. No abstract available.

    PubMed 19409872

  • Qiu S, Shi S, Ping H, Zhou S, Wang H, Yang B. Efficacy of Ivabradine versus beta-Blockers for Heart Rate Reduction during Computed Tomography Coronary Angiography: A Meta-Analysis of Randomized Controlled Trials. Cardiology. 2016;135(3):133-140. doi: 10.1159/000447236. Epub 2016 Jun 22.

    PubMed 27328446

  • Maffei E, Palumbo AA, Martini C, Tedeschi C, Tarantini G, Seitun S, Ruffini L, Aldrovandi A, Weustink AC, Meijboom WB, Mollet NR, Krestin GP, de Feyter PJ, Cademartiri F. "In-house" pharmacological management for computed tomography coronary angiography: heart rate reduction, timing and safety of different drugs used during patient preparation. Eur Radiol. 2009 Dec;19(12):2931-40. doi: 10.1007/s00330-009-1509-0.

    PubMed 19597820

  • Degertekin M, Gemici G, Kaya Z, Bayrak F, Guneysu T, Sevinc D, Mutlu B, Aytaclar S. Safety and efficacy of patient preparation with intravenous esmolol before 64-slice computed tomography coronary angiography. Coron Artery Dis. 2008 Feb;19(1):33-6. doi: 10.1097/MCA.0b013e3282f27c20.

    PubMed 18281813

  • Shapiro MD, Pena AJ, Nichols JH, Worrell S, Bamberg F, Dannemann N, Abbara S, Cury RC, Brady TJ, Hoffmann U. Efficacy of pre-scan beta-blockade and impact of heart rate on image quality in patients undergoing coronary multidetector computed tomography angiography. Eur J Radiol. 2008 Apr;66(1):37-41. doi: 10.1016/j.ejrad.2007.05.006. Epub 2007 Jun 22.

    PubMed 17587526

  • Rochitte CE, Azevedo GS, Shiozaki AA, Azevedo CF, Kalil Filho R. Diltiazem as an alternative to beta-blocker in coronary artery computed tomography angiography. Arq Bras Cardiol. 2012 Aug;99(2):706-13. doi: 10.1590/s0066-782x2012005000059. Epub 2012 Jun 26. English, Portuguese.

    PubMed 22735866

  • Roberts WT, Wright AR, Timmis JB, Timmis AD. Safety and efficacy of a rate control protocol for cardiac CT. Br J Radiol. 2009 Apr;82(976):267-71. doi: 10.1259/bjr/24574758. Epub 2008 Dec 19.

    PubMed 19098083

  • Bois P, Bescond J, Renaudon B, Lenfant J. Mode of action of bradycardic agent, S 16257, on ionic currents of rabbit sinoatrial node cells. Br J Pharmacol. 1996 Jun;118(4):1051-7. doi: 10.1111/j.1476-5381.1996.tb15505.x.

    PubMed 8799581

  • DiFrancesco D, Camm JA. Heart rate lowering by specific and selective I(f) current inhibition with ivabradine: a new therapeutic perspective in cardiovascular disease. Drugs. 2004;64(16):1757-65. doi: 10.2165/00003495-200464160-00003.

    PubMed 15301560

  • Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JGF, Coats AJS, Falk V, Gonzalez-Juanatey JR, Harjola VP, Jankowska EA, Jessup M, Linde C, Nihoyannopoulos P, Parissis JT, Pieske B, Riley JP, Rosano GMC, Ruilope LM, Ruschitzka F, Rutten FH, van der Meer P; ESC Scientific Document Group. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2016 Jul 14;37(27):2129-2200. doi: 10.1093/eurheartj/ehw128. Epub 2016 May 20. No abstract available.

    PubMed 27206819

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Metoprolol tartrate, Ivabradine and Diltiazem in people with Heart Rate and Coronary Computed Tomography Angiography, run by Mahidol University at 1 site in Thailand.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 17 May 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Thailand. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Prichapol Thantassanee, M.D. (+66896754200, char_uc0093@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percent of patient achieving target heart rate (HR) (time frame: 3 hours). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05261464, which also lists 21 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 May 2022; AzTrials last refreshed its copy on 3 Nov 2026.

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