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Atrial Substrate Modification With Aggressive Blood Pressure Lowering to Prevent AF (SMAC AF)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Nova Scotia Health Research Foundation
Information provided by (Responsible Party):
Ratika Parkash, Nova Scotia Health Authority
ClinicalTrials.gov Identifier:
NCT00438113
First received: February 7, 2007
Last updated: June 6, 2016
Last verified: June 2016
  Purpose
Atrial fibrillation (AF) is a very common arrhythmia causing many symptoms resulting in numerous hospitalizations. Catheter ablation is a technique that has evolved significantly to improve symptomatic recurrences, but does not offer a 100% cure rate. We hypothesize that the use of aggressive BP lowering will reduce the rate of recurrent AF after catheter ablation for AF. We plan a randomized clinical trial of aggressive BP lowering versus standard BP control to investigate this.

Condition Intervention Phase
Atrial Fibrillation
Drug: Aggressive Blood Pressure control
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Atrial Substrate Modification With Aggressive Blood Pressure Lowering to Prevent AF

Resource links provided by NLM:


Further study details as provided by Nova Scotia Health Authority:

Primary Outcome Measures:
  • Time to symptomatic AF/atrial tachycardia (AT)/atrial flutter (AFl) lasting > 30 seconds more than 3 months post ablation. [ Time Frame: at least 3 months post catheter ablation ] [ Designated as safety issue: No ]
    This has been altered since the inception of the study to include atrial tachycardia and atrial flutter, as there have been changes to how ablation is performed since the study began. Specifically, the STAR AF2 study found that PVI is similar to PVI in addition to either complex fractionated electrogram ablation or PVI in addition to linear ablation. Given this, the occurrence of AT/AFL was thought to be iatrogenic and occur as a consequence of various ablation strategies, rather than to the substrate, hence was excluded from the primary endpoint. Given the change in strategy of ablation, the inclusion of AT/AFl in the primary outcome is now necessary as it may reflect change in substrate, rather than ablation strategy, as previously thought. In addition, from a patient perspective, the occurence of AT/AFl is indistinguishable from a symptoms point of view.


Secondary Outcome Measures:
  • Any recurrent atrial fibrillation/atrial tachycardia/atrial flutter post randomization [ Time Frame: up to 30 months post randomization ] [ Designated as safety issue: No ]
  • Recurrent atrial fibrillation/atrial tachycardia/atrial flutter (symptomatic or asymptomatic) post ablation [ Time Frame: up to 30 months post randomization ] [ Designated as safety issue: No ]
  • atrial fibrillation/atrial tachycardia/atrial flutter burden (pre and post ablation) [ Time Frame: up to 30 months post randomization ] [ Designated as safety issue: No ]
  • Generic and disease specific quality of life [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Correlation of BNP and CRP and recurrence of atrial fibrillation/atrial tachycardia/atrial flutter [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Recurrent AF ablation therapy [ Time Frame: up to 30 months post randomization ] [ Designated as safety issue: No ]
  • Visits to the ER or hospitalization for atrial arrhythmia [ Time Frame: up to 30 months post randomization ] [ Designated as safety issue: No ]
  • Thromboembolic events [ Time Frame: up to 30 months post randomization ] [ Designated as safety issue: No ]

Enrollment: 184
Study Start Date: December 2009
Estimated Study Completion Date: November 2016
Estimated Primary Completion Date: October 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Aggressive Blood Pressure control

The experimental arm will receive open label therapy to achieve a target systolic blood pressure less than or equal to 120 mmHg.

If the average BP is found to be > 120 mmHg at the baseline, telephone or clinic followup visits, treatment will be recommended based on the following regimen (For details, please see Appendix 4):

Step 1 - Accupril, titrated to maximum tolerated dose, beginning at 20 mg po od followed by 40 mg successively Step 2 - combination of Accupril with Hydrochlorothiazide 12.5 mg po od. Step 3 - Addition of Atenolol 50 mg po od. Step 4 - Addition of Norvasc 2.5-10 mg po od. Step 5 - Addition of Terazosin 1 mg po od.

Drug: Aggressive Blood Pressure control
Aggressive Blood Pressure therapy, alone or combination therapy, to reach a target BP equal to or less than 120/80 mmHg
Other Names:
  • Accupril
  • Atenolol
  • Norvasc
  • Terazosin
  • Hydrochlorothiazide
No Intervention: Standard Blood Pressure control
Treatment will be carried out as per the CHEP guidelines. These patients may require ACEi or ARBs for their treatment. No changes to their drug regimen will be made as long as BP measurements are congruent with current guidelines. These modifications will be made as per standard practice by the physician who is primarily involved with their care (this may be a family physician or a specialist, depending on the patient). Patients with diabetes in the standard arm will be treated to a target BP of <130/80 as per the CHEP guidelines.

Detailed Description:

Background: Atrial fibrillation (AF) is the most common sustained arrhythmia and is associated with significant morbidity, necessitating treatment. Radiofrequency ablation for atrial fibrillation/flutter has evolved significantly and is the closest we have come to a 'cure' for these dysrhythmias. Recurrence of atrial fibrillation in those who have undergone radiofrequency ablation as treatment AF is up to 40% at one year and higher in those with persistent AF. Hypertension is a potent risk factor for AF, but recent studies have demonstrated that even modest increases in BP may lead to a higher incidence of AF. There is no clinical trial evidence to date that has investigated aggressive BP control in patients post radiofrequency ablation for AF to prevent recurrent AF.

Objective: We propose to determine if aggressive BP control reduces recurrent AF post ablation.

Hypothesis: Aggressive BP lowering will reduce the incidence of recurrent AF post ablation.

Research Plan:

Study Design. This will be a randomized open label trial in patients who are post catheter ablation for atrial fibrillation. Randomization to either aggressive BP lowering or standard BP control will occur three to six months prior to the procedure.

Study Population. Patients will be included if they have persistent or high burden paroxysmal (refractory to class 1 or 3 antiarrhythmic medication) and intend to have a catheter ablation procedure for AF.

Followup. Patients will be followed at 3 month intervals for the first year, then every 6 months to a maximum of 30 months or the common study end date has been reached (1 year post randomization for the last patient enrolled).

Statistical Analysis. Kaplan-Meier analysis of the primary outcome will be performed. A Cox proportional hazards model will be constructed to assess the effect of variables chosen a priori on the primary outcome.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Documented systolic blood pressure greater than or equal to 130 mmHg
  • Undergoing planned catheter ablation for persistent AF (lasting > 7 days and < 365 days or requiring electrical or chemical cardioversion) OR High burden paroxysmal AF > 6 months (greater than or equal to 3 symptomatic episdes in past 6 months and refractory or inteolerant to at least 1 class 1 or 3 antiarrhythmic)

Exclusion Criteria:

  • Permanent atrial fibrillation
  • Contraindication to Accupril or any other ACE-I
  • Women of child-bearing potential
  • Life expectancy less than 1 year
  • Less than 18 years of age
  • Unable to give informed consent
  • Known moderate to several renal dysfunction (eGFR < 30 ml/min/1.73m2)
  • Prior AF catheter ablation
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00438113

Locations
Canada, Nova Scotia
QE II Health Sciences Centre
Halifax, Nova Scotia, Canada, B3H 3A7
Sponsors and Collaborators
Nova Scotia Health Authority
Nova Scotia Health Research Foundation
Investigators
Principal Investigator: Ratika Parkash, MD MSc Dalhousie University/QEII HSC
  More Information

Responsible Party: Ratika Parkash, Staff Cardiologist, Electrophysiology, Nova Scotia Health Authority
ClinicalTrials.gov Identifier: NCT00438113     History of Changes
Other Study ID Numbers: RP-001 
Study First Received: February 7, 2007
Last Updated: June 6, 2016
Health Authority: Canada: Ethics Review Committee
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by Nova Scotia Health Authority:
blood pressure
atrial fibrillation
catheter ablation

Additional relevant MeSH terms:
Atrial Fibrillation
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Atenolol
Quinapril
Hydrochlorothiazide
Amlodipine
Terazosin
Anti-Arrhythmia Agents
Antihypertensive Agents
Sympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Adrenergic beta-1 Receptor Antagonists
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Diuretics
Natriuretic Agents
Sodium Chloride Symporter Inhibitors
Membrane Transport Modulators
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Calcium Channel Blockers

ClinicalTrials.gov processed this record on December 09, 2016