NCT02695992

Brief Summary

The RATAF II study is a randomized, prospective, parallel group study, designed to compare the effects of two different drug regimens for rate control in permanent AF (atrial fibrillation). We will investigate on the difference in effects on exercise capacity, biomarkers (NT-proBNP (N-terminal pro-brain natriuretic peptide), troponins, hs-CRP), heart rate, echocardiographic measurements and symptoms. Our main hypothesis is that six months' treatment with the calcium channel blocker diltiazem will lower NT-proBNP and increase exercise capacity (peak VO2) compared to treatment with the beta blocker metoprolol in permanent AF.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
122

participants targeted

Target at P25-P50 for phase_4 atrial-fibrillation

Timeline
Completed

Started Feb 2016

Longer than P75 for phase_4 atrial-fibrillation

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 28, 2015

Completed
9 months until next milestone

Study Start

First participant enrolled

February 1, 2016

Completed
1 month until next milestone

First Posted

Study publicly available on registry

March 2, 2016

Completed
5.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2021

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

November 12, 2021

Completed
Last Updated

January 5, 2022

Status Verified

January 1, 2022

Enrollment Period

5.7 years

First QC Date

April 28, 2015

Last Update Submit

January 4, 2022

Conditions

Atrial FibrillationPermanent Atrial Fibrillation

Keywords

Rate control in atrial fibrillationBeta blockersCalcium channel blockersPermanent atrial fibrillationManagement of atrial fibrillationAtrial fibrillation and biomarkersArrhythmias, cardiacHeart DiseasesPathological processesDiltiazemMetoprololAdrenergic AgentsAdrenergic AntagonistsAdrenergic beta-1 Receptor AntagonistsAdrenergic beta-AntagonistsAnti-Arrhythmia AgentsAntihypertensive AgentsAutonomic AgentsCardiovascular AgentsMembrane Transport ModulatorsMolecular Mechanisms of Pharmacological ActionNeurotransmitter AgentsPeripheral Nervous System AgentsPhysiological Effects of DrugsSympatholyticsTherapeutic UsesVasodilator AgentsTroponinsNT-proBNPBiomarkers

Outcome Measures

Primary Outcomes (2)

  • Levels of NT-proBNP

    Levels of NT-proBNP will be measured at baseline and after 4 weeks to assess change

    4 weeks

  • Levels of NT-proBNP

    Levels of NT-proBNP will be measured after 6 months

    6 months

Secondary Outcomes (26)

  • Exercise capacity defined as peak VO2

    4 weeks

  • Exercise capacity defined as peak VO2

    6 months

  • Ventricular heart rate

    4 weeks

  • Ventricular heart rate

    6 months

  • Other biomarkers

    4 weeks

  • +21 more secondary outcomes

Other Outcomes (2)

  • Blood pressure

    4 weeks

  • Blood pressure

    6 months

Study Arms (2)

Metoprolol

ACTIVE COMPARATOR

Metoprolol, extended release tablets. 100 mg daily

Drug: Metoprolol

Diltiazem

ACTIVE COMPARATOR

Diltiazem, extended release tablets. 360 mg daily

Drug: Diltiazem

Interventions

MetoprololDRUG

Dosage 100 mg o.d.

Also known as: Selo-Zok Metoprolol Astra Zeneca depot
Metoprolol
DiltiazemDRUG

Dosage 360 mg o.d.

Also known as: Cardizem Diltiazem Uno depot
Diltiazem

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Above 18 years of age
  • Symptomatic, permanent AF of at least three months duration
  • Resting heart rate ≥80 bpm
  • Signed informed consent

You may not qualify if:

  • Congestive heart failure
  • Ischemic heart disease
  • Hypotension (Systolic blood pressure \<100 mmHg)
  • Treatment with class I or III antiarrhythmic drugs
  • Severe hepatic or renal failure
  • Pregnancy or lactation
  • Hypersensitivity or contradictions to study drugs
  • Atrio-ventricular conduction disturbances
  • Thyrotoxicosis
  • Life limiting disease or substance abuse which may affect participation

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Vestre Viken Hospital Trust, Baerum Hospital

Rud, Akershus, 1309, Norway

Location

Related Publications (8)

  • Ulimoen SR, Enger S, Pripp AH, Abdelnoor M, Arnesen H, Gjesdal K, Tveit A. Calcium channel blockers improve exercise capacity and reduce N-terminal Pro-B-type natriuretic peptide levels compared with beta-blockers in patients with permanent atrial fibrillation. Eur Heart J. 2014 Feb;35(8):517-24. doi: 10.1093/eurheartj/eht429. Epub 2013 Oct 17.

    PMID: 24135831BACKGROUND

  • Ulimoen SR, Enger S, Carlson J, Platonov PG, Pripp AH, Abdelnoor M, Arnesen H, Gjesdal K, Tveit A. Comparison of four single-drug regimens on ventricular rate and arrhythmia-related symptoms in patients with permanent atrial fibrillation. Am J Cardiol. 2013 Jan 15;111(2):225-30. doi: 10.1016/j.amjcard.2012.09.020. Epub 2012 Oct 27.

    PMID: 23111138BACKGROUND

  • Go AS, Hylek EM, Phillips KA, Chang Y, Henault LE, Selby JV, Singer DE. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. JAMA. 2001 May 9;285(18):2370-5. doi: 10.1001/jama.285.18.2370.

    PMID: 11343485BACKGROUND

  • Van Gelder IC, Groenveld HF, Crijns HJ, Tuininga YS, Tijssen JG, Alings AM, Hillege HL, Bergsma-Kadijk JA, Cornel JH, Kamp O, Tukkie R, Bosker HA, Van Veldhuisen DJ, Van den Berg MP; RACE II Investigators. Lenient versus strict rate control in patients with atrial fibrillation. N Engl J Med. 2010 Apr 15;362(15):1363-73. doi: 10.1056/NEJMoa1001337. Epub 2010 Mar 15.

    PMID: 20231232BACKGROUND

  • European Heart Rhythm Association; European Association for Cardio-Thoracic Surgery; Camm AJ, Kirchhof P, Lip GY, Schotten U, Savelieva I, Ernst S, Van Gelder IC, Al-Attar N, Hindricks G, Prendergast B, Heidbuchel H, Alfieri O, Angelini A, Atar D, Colonna P, De Caterina R, De Sutter J, Goette A, Gorenek B, Heldal M, Hohloser SH, Kolh P, Le Heuzey JY, Ponikowski P, Rutten FH. Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Eur Heart J. 2010 Oct;31(19):2369-429. doi: 10.1093/eurheartj/ehq278. Epub 2010 Aug 29. No abstract available.

    PMID: 20802247BACKGROUND

  • Ulimoen SR, Enger S, Norseth J, Pripp AH, Abdelnoor M, Arnesen H, Gjesdal K, Tveit A. Improved rate control reduces cardiac troponin T levels in permanent atrial fibrillation. Clin Cardiol. 2014 Jul;37(7):422-7. doi: 10.1002/clc.22281. Epub 2014 Apr 3.

    PMID: 24700386BACKGROUND

  • Van Gelder IC, Hobbelt AH, Mulder BA, Rienstra M. Rate control in atrial fibrillation: many questions still unanswered. Circulation. 2015 Oct 27;132(17):1597-9. doi: 10.1161/CIRCULATIONAHA.115.018952. Epub 2015 Sep 17. No abstract available.

    PMID: 26384161BACKGROUND

  • Enge K, Ulimoen SR, Enger S, Onarheim S, Olufsen M, Pripp AH, Steinsvik T, Hall C, Hetland M, Tveit A. Effects of diltiazem and metoprolol on levels of high-sensitivity troponin I in patients with permanent atrial fibrillation: a randomized trial. BMC Cardiovasc Disord. 2025 Mar 14;25(1):181. doi: 10.1186/s12872-025-04574-2.

    PMID: 40087560DERIVED

MeSH Terms

Conditions

Atrial FibrillationArrhythmias, CardiacHeart DiseasesPathologic Processes

Interventions

MetoprololDiltiazem

Condition Hierarchy (Ancestors)

Cardiovascular DiseasesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

PhenoxypropanolaminesPropanolaminesAmino AlcoholsAlcoholsOrganic ChemicalsPropanolsAminesBenzazepinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic Compounds

Study Officials

  • Sara Reinvik Ulimoen, MD PhD

    Vestre Viken HF Baerum Hospital

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
MD PhD postdoc fellow

Study Record Dates

First Submitted

April 28, 2015

First Posted

March 2, 2016

Study Start

February 1, 2016

Primary Completion

October 1, 2021

Study Completion

November 12, 2021

Last Updated

January 5, 2022

Record last verified: 2022-01

Data Sharing

IPD Sharing
Will not share

Locations

NO(1)