Atrial Fibrillation, ParoxysmalPhase 4CANREN-AFNCT03536806
Clinical Efficacy of Potassium Canrenoate in Sinus Rhythm Restoration Among Patients With Atrial Fibrillation.
A Phase 4 study testing Saline 0.9% and Canrenone in people with Atrial Fibrillation, Paroxysmal, run by National Institute of Cardiology, Warsaw, Poland.
Trial summary
The purpose of this randomized, double blind, placebo-controlled, superiority clinical trial was to assess clinical efficacy of potassium canrenoate - canrenone in rapid conversion of atrial fibrillation to sinus rhythm. Read more about this study
- Who is it for?
- Ages 40 to 75 years
- Conditions the study is for
- Atrial Fibrillation, Paroxysmal
- What is being tested?
- Saline 0.9% and Canrenone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- No sites listed yet
- Study dates
- Jun 2018to Dec 2020
- 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 40 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- written informed consent for enrolment
- patients aged between 40 and 75 years
- atrial fibrillation episode lasting for less than 48 hours, documented by the ECG
- potassium plasma levels < 4.5 mmol/l
- blood pressure > 120/80 mmHg
- stable cardiopulmonary status (according to attending physician's assessment)
- in case of left ventricle injury suspicion or unclear medical history of cardiac insufficiency, enrolment will be possible after echocardiographic examination
Who cannot join
- no written informed consent for enrollment
- allergy to canrenone
- cardiac insufficiency or LVEF (left ventricular ejection fraction) < 40%
- systolic BP < 120/80 mmHg
- history of canrenone treatment in the 30 days before enrollment
- average QRS rate > 160 p.m.
Show all 11Show fewer
- advanced hepatic or renal failure
- history of acute coronary syndrome, CABG (coronary artery bypass grafting), TIA (transient ischemic attack) or stroke within the previous 30 days
- pre-excitation syndrome (which has not been treated with accessory pathway ablation).
- atrial fibrillation due to a valvular heart disease
- atrial fibrillation episode resulting in myocardial ischemia (chest pain, ischemic changes in the ECG)
Trial locations and contacts
No sites are listed yet.
About this study
Official title: Clinical Efficacy of Potassium Canrenoate - Canrenone in Sinus Rhythm Restoration Among Patients With Atrial Fibrillation and Elevated Blood Pressure - a Pilot Randomized Controlled Trial.
The purpose of this randomized, double blind, placebo-controlled, superiority clinical trial was to assess clinical efficacy of potassium canrenoate - canrenone in rapid conversion of atrial fibrillation to sinus rhythm.
Read the detailed description
Canrenone is a specific antagonist of aldosterone. It is a competitive inhibitor of aldosterone receptors and inhibits the effects of aldosterone. Spironolactone is a prodrug which is active after its conversion into canrenone. By inhibiting the effects of aldosterone it increases aqueous and sodium diuresis and is classified as a diuretic. It decreases urinary elimination of potassium and increases urinary excretion of calcium. Canrenone is used for the treatment of primary or secondary hyperaldosteronism, edema and ascites of congestive heart failure and cirrhosis, and in the treatment of the arterial hypertension. Current evidence supports renin-angiotensin-alodsterone (RAAS) inhibition: angiotensin-converting-enzyme inhibitors (ACE-I), angiotensin receptor blockers (ARB) or, potentially, mineralocorticoid receptor antagonists (MRA) as an upstream therapy for atrial fibrillation (AF) management. It has been demonstrated that plasma aldosterone concentration may be increased in patients with AF episode, and it lowers after cardioversion. Only canrenone (potassium canrenoate) may be administered intravenously. Canrenone increases plasma level of potassium, lowers blood pressure and reduces preload at the same time.
To show superiority of canrenone over placebo a sample size of 80 patients was calculated based on following assumptions: two-tailed test, a type I error of 0.01, a power of 90%, efficacy of placebo 5%, efficacy of canrenone 50% and 20% drop-out rate to fulfill the criteria of intention-to-treat analysis. Due to presumed lack of statistical power the secondary end points and safety endpoints will be considered exploratory.
- Conditions
- Atrial Fibrillation, Paroxysmal
- Being tested
- Saline 0.9%, Canrenone
- Keywords
- Pharmacological cardioversion, Canrenone
- Medical subject headings
- Atrial Fibrillation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Saline 0.9%Drug
Also called saline 0.9% in bolus of 10 cm3
Patients assigned to control group will be administered saline 0.9% in bolus of 10 cm3 within 2-3 minutes. BP will be measured before injection.
CanrenoneDrug
Also called canrenone in bolus of 200 mg diluted to 10 cm3
Patients assigned to canrenone group will be administered canrenone in bolus of 200 mg diluted to 10 cm3 within 2-3 minutes in one dose. Drug administration will be stopped in case of serious adverse event. Further treatment of the patient will depend on clinical condition and will follow appropriate clinical guidelines.
| Study group | Role | What they receive |
|---|---|---|
| Placebo Comparator: Placebo | Placebo comparator | Any patient fulfilling the inclusion criteria will be prepared to pharmacological cardioversion in a standard way comprising of standard baseline 12-lead ECG, continuous ECG monitoring, periodic noninvasive blood pressure monitoring (BP) and iv line. Patients assigned to control group will be administered saline 0.9% in bolus of 10 cm3 within 2-3 minutes. After drug administration the patient will be observed for 2 hours after the last dose with exit ECG and BP measure taken at the end of observation. Further treatment of the patient will depend on clinical condition and will follow appropriate clinical guidelines. Receives: Drug: Saline 0.9% |
| Experimental: canrenone | Experimental | Any patient fulfilling the inclusion criteria will be prepared to pharmacological cardioversion in a standard way comprising of standard baseline 12-lead ECG, continuous ECG monitoring, periodic noninvasive blood pressure monitoring (BP) and iv line. After administration of canrenone: dose 200 mg (1 ampule a 10 ml) within 2-3 minutes the patient will be observed for 2 hours after the dose with exit ECG and BP measure taken at the end of observation. Receives: Drug: Canrenone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Conversion of atrial fibrillation to sinus rhythm.
Conversion of atrial fibrillation to sinus rhythm confirmed in standard 12-lead ECG during observation period after first iv bolus.
Measured: Time Frame: 2 hours.
Secondary outcomes (4)
Time to conversion of atrial fibrillation to sinus rhythm.
Time to conversion of atrial fibrillation to sinus rhythm in minutes since injection.
Measured: Time Frame: 2 hours.
Atrial fibrillation recurrence within observation period.
Atrial fibrillation recurrence within observation period.
Measured: Time Frame: 2 hours.
Serious adverse reactions.
Serious adverse reactions, which refer to every event requiring admission to a hospital or extended observation.
Measured: Time Frame: 24 hours.
Safety outcome (exploratory analysis).
hypotension < 90 mm Hg, cardiac conduction abnormalities, new arrhythmia occurrence, other
Measured: Time Frame: 24 hours.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 May 2018
- Study startJun 2018 (estimated)
- Primary completionDec 2019 (estimated)
- Study completionDec 2020 (estimated)
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 Fibrillation, ParoxysmalStudies 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Parallel Assignment
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Institute of Cardiology, Warsaw, Poland
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Rafał Dąbrowski, National Institute of Cardiology, Warsaw, Poland
- Investigators
- Rafał Dąbrowski, MD, PhD, Principal investigator, Institute of CardiologyTomasz Hryniewiecki, MD, PhD, Study chair, Institute of Cardiology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03536806
- Sponsor's protocol ID
- 2.62/VII/16
- Acronym
- CANREN-AF
- Status last verified
- May 2018
- First submitted
- 12 May 2018
- Last updated
- 25 May 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Dabrowski R, Segiet-Swiecicka A, Sawicki S, Kowalik I, Jaworski K, Farkowski M, Kubaszek-Kornatowska A, Michalek P, Dluzniewski M, Szwed H, Hryniewiecki T, Karwowski J; CANREN-AF investigators. Clinical Efficacy of Canrenone in Restoring Sinus Rhythm in Patients With Atrial Fibrillation-A Pilot, Randomized, Double-Blind Study. J Cardiovasc Pharmacol Ther. 2025 Jan-Dec;30:10742484251356361. doi: 10.1177/10742484251356361. Epub 2025 Jul 29.
PubMed 40734383Dabrowski R, Syska P, Maczynska J, Farkowski M, Sawicki S, Kubaszek-Kornatowska A, Michalek P, Kowalik I, Szwed H, Hryniewiecki T. Clinical efficacy of potassium canreonate-canrenone in sinus rhythm restoration among patients with atrial fibrillation - a protocol of a pilot, randomized, double -blind, placebo-controlled study (CANREN-AF trial). Trials. 2020 May 12;21(1):397. doi: 10.1186/s13063-020-04277-3.
PubMed 32398047
Study at a glance
From the registry record, last updated by the sponsor on 25 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Efficacy of Potassium Canrenoate - Canrenone in Sinus Rhythm Restoration Among Patients With Atrial Fibrillation and Elevated Blood Pressure - a Pilot Randomized Controlled Trial.
- ClinicalTrials.gov ID
- NCT03536806
- Acronym / sponsor ID
- CANREN-AF / 2.62/VII/16
- Conditions
- Atrial Fibrillation, Paroxysmal
- Keywords
- Pharmacological cardioversion, Canrenone
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- National Institute of Cardiology, Warsaw, PolandUniversity, hospital or other
- Study start
- Jun 2018 (estimated)
- Primary completion
- Dec 2019 (estimated)
- Study completion
- Dec 2020 (estimated)
- First posted
- 25 May 2018 (actual)
- 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.
The purpose of this randomized, double blind, placebo-controlled, superiority clinical trial was to assess clinical efficacy of potassium canrenoate - canrenone in rapid conversion of atrial fibrillation to sinus rhythm.
Detailed description
Canrenone is a specific antagonist of aldosterone. It is a competitive inhibitor of aldosterone receptors and inhibits the effects of aldosterone. Spironolactone is a prodrug which is active after its conversion into canrenone. By inhibiting the effects of aldosterone it increases aqueous and sodium diuresis and is classified as a diuretic. It decreases urinary elimination of potassium and increases urinary excretion of calcium. Canrenone is used for the treatment of primary or secondary hyperaldosteronism, edema and ascites of congestive heart failure and cirrhosis, and in the treatment of the arterial hypertension. Current evidence supports renin-angiotensin-alodsterone (RAAS) inhibition: angiotensin-converting-enzyme inhibitors (ACE-I), angiotensin receptor blockers (ARB) or, potentially, mineralocorticoid receptor antagonists (MRA) as an upstream therapy for atrial fibrillation (AF) management. It has been demonstrated that plasma aldosterone concentration may be increased in patients with AF episode, and it lowers after cardioversion. Only canrenone (potassium canrenoate) may be administered intravenously. Canrenone increases plasma level of potassium, lowers blood pressure and reduces preload at the same time.
To show superiority of canrenone over placebo a sample size of 80 patients was calculated based on following assumptions: two-tailed test, a type I error of 0.01, a power of 90%, efficacy of placebo 5%, efficacy of canrenone 50% and 20% drop-out rate to fulfill the criteria of intention-to-treat analysis. Due to presumed lack of statistical power the secondary end points and safety endpoints will be considered exploratory.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
- Model description
- Parallel Assignment
| Arm | Type | Receives |
|---|---|---|
| Placebo Comparator: Placebo | Placebo comparator | Drug: Saline 0.9%Any patient fulfilling the inclusion criteria will be prepared to pharmacological cardioversion in a standard way comprising of standard baseline 12-lead ECG, continuous ECG monitoring, periodic noninvasive blood pressure monitoring (BP) and iv line. Patients assigned to control group will be administered saline 0.9% in bolus of 10 cm3 within 2-3 minutes. After drug administration the patient will be observed for 2 hours after the last dose with exit ECG and BP measure taken at the end of observation. Further treatment of the patient will depend on clinical condition and will follow appropriate clinical guidelines. |
| Experimental: canrenone | Experimental | Drug: CanrenoneAny patient fulfilling the inclusion criteria will be prepared to pharmacological cardioversion in a standard way comprising of standard baseline 12-lead ECG, continuous ECG monitoring, periodic noninvasive blood pressure monitoring (BP) and iv line. After administration of canrenone: dose 200 mg (1 ampule a 10 ml) within 2-3 minutes the patient will be observed for 2 hours after the dose with exit ECG and BP measure taken at the end of observation. |
Who may qualify
- Ages
- 40 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- written informed consent for enrolment
- patients aged between 40 and 75 years
- atrial fibrillation episode lasting for less than 48 hours, documented by the ECG
- potassium plasma levels < 4.5 mmol/l
- blood pressure > 120/80 mmHg
Key exclusion criteria (11 listed)
- no written informed consent for enrollment
- allergy to canrenone
- cardiac insufficiency or LVEF (left ventricular ejection fraction) < 40%
- systolic BP < 120/80 mmHg
- history of canrenone treatment in the 30 days before enrollment
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 |
|---|---|---|
| Saline 0.9%Also: saline 0.9% in bolus of 10 cm3Patients assigned to control group will be administered saline 0.9% in bolus of 10 cm3 within 2-3 minutes. BP will be measured before injection. | Drug | Placebo Comparator: Placebo |
| CanrenoneAlso: canrenone in bolus of 200 mg diluted to 10 cm3Patients assigned to canrenone group will be administered canrenone in bolus of 200 mg diluted to 10 cm3 within 2-3 minutes in one dose. Drug administration will be stopped in case of serious adverse event. Further treatment of the patient will depend on clinical condition and will follow appropriate clinical guidelines. | Drug | Experimental: canrenone |
Primary outcome
Conversion of atrial fibrillation to sinus rhythm.
Time frame: Time Frame: 2 hours.
Conversion of atrial fibrillation to sinus rhythm confirmed in standard 12-lead ECG during observation period after first iv bolus.
4 secondary outcomes
Time to conversion of atrial fibrillation to sinus rhythm.
Time frame: Time Frame: 2 hours.
Atrial fibrillation recurrence within observation period.
Time frame: Time Frame: 2 hours.
Serious adverse reactions.
Time frame: Time Frame: 24 hours.
Safety outcome (exploratory analysis).
Time frame: Time Frame: 24 hours.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 May 2018.
- Derived from this study: PubMed 40734383Dabrowski R, Segiet-Swiecicka A, Sawicki S, Kowalik I, Jaworski K, Farkowski M, Kubaszek-Kornatowska A, Michalek P, Dluzniewski M, Szwed H, Hryniewiecki T, Karwowski J; CANREN-AF investigators. Clinical Efficacy of Canrenone in Restoring Sinus Rhythm in Patients With Atrial Fibrillation-A Pilot, Randomized, Double-Blind Study. J Cardiovasc Pharmacol Ther. 2025 Jan-Dec;30:10742484251356361. doi: 10.1177/10742484251356361. Epub 2025 Jul 29.
- Derived from this study: PubMed 32398047Dabrowski R, Syska P, Maczynska J, Farkowski M, Sawicki S, Kubaszek-Kornatowska A, Michalek P, Kowalik I, Szwed H, Hryniewiecki T. Clinical efficacy of potassium canreonate-canrenone in sinus rhythm restoration among patients with atrial fibrillation - a protocol of a pilot, randomized, double -blind, placebo-controlled study (CANREN-AF trial). Trials. 2020 May 12;21(1):397. doi: 10.1186/s13063-020-04277-3.
- Individual participant dataSharing planned: Undecided
Related trials for Atrial Fibrillation, Paroxysmal
Active, not recruiting
Horizon 360 Protocol for the Treatment of Paroxysmal Atrial Fibrillation With the Sphere-360™ Catheter and Affera™ Mapping and Ablation System (Horizon 360)
Paroxysmal AF
RecruitingObservational study
A Study of Varipulse Catheter in Participants With Paroxysmal Atrial Fibrillation Under Optimized Sedation
Atrial Fibrillation
Recruiting
A Study Assessing Arrhythmia Mapping With a Multi-Electrode Mapping Catheter
Scar-related Atrial Tachycardia, Persistent Atrial Fibrillation
Active, not recruiting
A Study of VARIPULSE Catheter and TRUPULSE Generator With VARIPULSE Pro Software in Participants With PAF or PsAF
Atrial Fibrillation
Not yet recruitingObservational study
Catheter Ablation Using a Novel Navigation and Imaging System
Paroxysmal Atrial Fibrillation
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.
Rafał Dąbrowski, MD, PhD principal investigator
Institute of Cardiology
Tomasz Hryniewiecki, MD, PhD study chair
Institute of Cardiology
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Saline 0.9% and Canrenone in people with Atrial Fibrillation, Paroxysmal, run by National Institute of Cardiology, Warsaw, Poland.
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 7 inclusion and 11 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 25 May 2018. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. 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 Rafał Dąbrowski, MD, PhD (+48 601250732, rdabrowski45@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Conversion of atrial fibrillation to sinus rhythm. (time frame: Time Frame: 2 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 NCT03536806, 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 25 May 2018.