Atrial FibrillationPhase 4SMAC AFNCT00438113
Atrial Substrate Modification With Aggressive Blood Pressure Lowering to Prevent AF
A Phase 4 study of Atrial Fibrillation, run by Nova Scotia Health Authority at 1 site in Canada.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Atrial Fibrillation
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 184 participants
- Where
- 1 siteCanada
- Study dates
- Dec 2009to Sep 2016
- 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
- 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)
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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.
- Conditions
- Atrial Fibrillation
- Being tested
- Aggressive Blood Pressure control
- Keywords
- blood pressure, atrial fibrillation, catheter ablation
- Medical subject headings
- Atrial Fibrillation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Aggressive Blood Pressure controlDrug
Also called Accupril, Atenolol, Norvasc, Terazosin
Aggressive Blood Pressure therapy, alone or combination therapy, to reach a target BP equal to or less than 120/80 mmHg
| Study group | Role | What they receive |
|---|---|---|
| Aggressive Blood Pressure control | Active comparator | 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. Receives: Drug: Aggressive Blood Pressure control |
| Standard Blood Pressure control | No intervention | 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to symptomatic AF/atrial tachycardia (AT)/atrial flutter (AFl) lasting > 30 seconds more than 3 months post ablation.
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.
Measured: at least 3 months post catheter ablation
Secondary outcomes (8)
Any recurrent atrial fibrillation/atrial tachycardia/atrial flutter post randomization
Measured: up to 30 months post randomization
Recurrent atrial fibrillation/atrial tachycardia/atrial flutter (symptomatic or asymptomatic) post ablation
Measured: up to 30 months post randomization
atrial fibrillation/atrial tachycardia/atrial flutter burden (pre and post ablation)
Measured: up to 30 months post randomization
Generic and disease specific quality of life
Measured: 12 months
Correlation of BNP and CRP and recurrence of atrial fibrillation/atrial tachycardia/atrial flutter
Measured: 12 months
Recurrent AF ablation therapy
Measured: up to 30 months post randomization
Visits to the ER or hospitalization for atrial arrhythmia
Measured: up to 30 months post randomization
Thromboembolic events
Measured: up to 30 months post randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2007 (estimated)
- Study startDec 2009
- Primary completionSep 2016
- Study completionSep 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Atrial FibrillationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 184 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nova Scotia Health Authority
- Sponsor type
- University, hospital or other
- Collaborators
- Nova Scotia Health Research Foundation
- Responsible party
- Principal investigator, Ratika Parkash, Nova Scotia Health Authority
- Investigators
- Ratika Parkash, MD MSc, Principal investigator, Dalhousie University/QEII HSC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00438113
- Sponsor's protocol ID
- RP-001
- Acronym
- SMAC AF
- Status last verified
- Jun 2017
- First submitted
- 7 Feb 2007
- Last updated
- 20 Jun 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Weng W, Choudhury R, Sapp J, Tang A, Healey JS, Nault I, Rivard L, Greiss I, Bernick J, Parkash R. The role of brain natriuretic peptide in atrial fibrillation: a substudy of the Substrate Modification with Aggressive Blood Pressure Control for Atrial Fibrillation (SMAC-AF) trial. BMC Cardiovasc Disord. 2021 Sep 16;21(1):445. doi: 10.1186/s12872-021-02254-5.
PubMed 34530738Parkash R, Wells GA, Sapp JL, Healey JS, Tardif JC, Greiss I, Rivard L, Roux JF, Gula L, Nault I, Novak P, Birnie D, Ha A, Wilton SB, Mangat I, Gray C, Gardner M, Tang ASL. Effect of Aggressive Blood Pressure Control on the Recurrence of Atrial Fibrillation After Catheter Ablation: A Randomized, Open-Label Clinical Trial (SMAC-AF [Substrate Modification With Aggressive Blood Pressure Control]). Circulation. 2017 May 9;135(19):1788-1798. doi: 10.1161/CIRCULATIONAHA.116.026230. Epub 2017 Feb 22.
PubMed 28228428
Study at a glance
From the registry record, last updated by the sponsor on 20 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Atrial Substrate Modification With Aggressive Blood Pressure Lowering to Prevent AF
- ClinicalTrials.gov ID
- NCT00438113
- Acronym / sponsor ID
- SMAC AF / RP-001
- Conditions
- Atrial Fibrillation
- Keywords
- blood pressure, atrial fibrillation, catheter ablation
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 184 participants (actual)
- Lead sponsor
- Nova Scotia Health AuthorityUniversity, hospital or other
- Collaborators
- Nova Scotia Health Research Foundation
- Study start
- Dec 2009
- Primary completion
- Sep 2016 (actual)
- Study completion
- Sep 2016 (actual)
- First posted
- 21 Feb 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Aggressive Blood Pressure control | Active comparator | Drug: Aggressive Blood Pressure controlThe 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. |
| Standard Blood Pressure control | No intervention | –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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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)
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Aggressive Blood Pressure controlAlso: Accupril, Atenolol, Norvasc, TerazosinAggressive Blood Pressure therapy, alone or combination therapy, to reach a target BP equal to or less than 120/80 mmHg | Drug | Aggressive Blood Pressure control |
Primary outcome
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
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.
8 secondary outcomes
Any recurrent atrial fibrillation/atrial tachycardia/atrial flutter post randomization
Time frame: up to 30 months post randomization
Recurrent atrial fibrillation/atrial tachycardia/atrial flutter (symptomatic or asymptomatic) post ablation
Time frame: up to 30 months post randomization
atrial fibrillation/atrial tachycardia/atrial flutter burden (pre and post ablation)
Time frame: up to 30 months post randomization
Generic and disease specific quality of life
Time frame: 12 months
Correlation of BNP and CRP and recurrence of atrial fibrillation/atrial tachycardia/atrial flutter
Time frame: 12 months
Recurrent AF ablation therapy
Time frame: up to 30 months post randomization
Visits to the ER or hospitalization for atrial arrhythmia
Time frame: up to 30 months post randomization
Thromboembolic events
Time frame: up to 30 months post randomization
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jun 2017.
- Derived from this study: PubMed 34530738Weng W, Choudhury R, Sapp J, Tang A, Healey JS, Nault I, Rivard L, Greiss I, Bernick J, Parkash R. The role of brain natriuretic peptide in atrial fibrillation: a substudy of the Substrate Modification with Aggressive Blood Pressure Control for Atrial Fibrillation (SMAC-AF) trial. BMC Cardiovasc Disord. 2021 Sep 16;21(1):445. doi: 10.1186/s12872-021-02254-5.
- Derived from this study: PubMed 28228428Parkash R, Wells GA, Sapp JL, Healey JS, Tardif JC, Greiss I, Rivard L, Roux JF, Gula L, Nault I, Novak P, Birnie D, Ha A, Wilton SB, Mangat I, Gray C, Gardner M, Tang ASL. Effect of Aggressive Blood Pressure Control on the Recurrence of Atrial Fibrillation After Catheter Ablation: A Randomized, Open-Label Clinical Trial (SMAC-AF [Substrate Modification With Aggressive Blood Pressure Control]). Circulation. 2017 May 9;135(19):1788-1798. doi: 10.1161/CIRCULATIONAHA.116.026230. Epub 2017 Feb 22.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ratika Parkash, MD MSc principal investigator
Dalhousie University/QEII HSC
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study of Atrial Fibrillation, run by Nova Scotia Health Authority at 1 site in Canada.
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 2 inclusion and 8 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: finished, as of the sponsor's last update on 20 Jun 2017. 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 Canada. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). 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 NCT00438113, which also lists 2 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 20 Jun 2017.