Atrial FibrillationAFISBIONCT03855540
Atrial Fibrillation in Relationship to Sleep Quality and Plasma Biomarkers
An observational study of Atrial Fibrillation, run by Premedix Academy at 4 sites in Slovakia.
Trial summary
A. Compare the plasmatic biomarkers between the cohort with and without AFib. B. Find sensitive and specific biomarkers that could be used for the diagnostic management of AFib. C. Compare the quality of sleep between the cohort with and without AFib by the means of sleeping quality questionnaire Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Atrial Fibrillation
- What is being tested?
- ECHOcardiography, Peripheral blood samples for plasmatic biomarkers and Athens insomnia scale questionnaire
- How many people
- 200 participants
- Where
- 4 sitesSlovakia
- Study dates
- 11 Apr 2018to 31 Dec 2019
- Phase
- Observational
- 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
Study population: Slovak hospitals and outpatients clinics
Who may be able to join
None listed.
Who cannot join
- Electrical cardioversion less than 7 days prior to inclusion
- Acute coronary syndrome less than 1 month prior to inclusion
- Cardiac surgery less than 3 months prior to inclusion
- Acute or decompensated heart failureat the time of inclusion
- Pregnancy
- Cardiomyopathy
Show all 14Show fewer
- Alcoholism (≥ 8 drinks/week)
- Thyrotoxicosis
- Renal Disease (Dialysis/ transplant/CrCl < 0,5ml/s)
- Liver disease (cirrhosis/ transaminase > 3x ULT/ bilirubin > 2x ULT)
- Mechanical proshetic valves
- Severe mitral stenosis
- Class I and IV antiarrhythmic drugs usage in last month
- Class III antiarrhythmic drugs usagein last 3 months
Trial locations and contacts
4 sites in 1 country.
Slovakia4 sites, 4 recruiting
- Recruiting
Allan Bohm
Bratislava, 81102
Allan Bohm, MD, 0259320111, allan.bohm@gmail.com
- Recruiting
East Slovak Institute of Cardiovascular Diseases
Košice
Marianna Vachalcová, MD, 421914241352, vachalcova@gmail.com
- Recruiting
Hospital
Malacky
Tomas Uher, MD, uher@gmail.com
- Recruiting
University hospital
Nitra
Peter Snopek, MD, snopek@gmail.com
Viera Kissová, MD
About this study
Official title: AFISBIO - Atrial Fibrillation in Relationship to Sleep Quality and Plasma Biomarkers.
- Compare the plasmatic biomarkers between the cohort with and without AFib.
- Find sensitive and specific biomarkers that could be used for the diagnostic management of AFib.
- Compare the quality of sleep between the cohort with and without AFib by the means of sleeping quality questionnaire
Read the detailed description
AFib is the most common sustained arrhythmia, associated with an increased risk of stroke, heart failure, and mortality. Despite the high prevalence, AFib may be asymptomatic and consequently subclinical. Detection of subclinical AFib is highly challenging as only a minority of the patients is diagnosed during a standard examinations with a 12 - lead ECG or a 24h ECG Holter monitoring. Documented AFib causes 15% of ischemic strokes, however approximately 25% of ischemic strokes is of an unknown etiology. It is believed that undetected subclinical AFib is responsible for these strokes. There is also evidence that asymptomatic AFib is associated with a higher incidence of strokes in comparison to symptomatic AFib.
Due to the fact that the standard ECG examination is not sufficient for AFib detection, various ECG screening methods have been introduced. Intermittent short ECG recording seems to be more effective than 24-hour Holter ECG in the detection of the arrhythmia however, it is not known whether it is superior to the 7 - day ECG Holter monitoring.
Plasmatic biomarkers might be of a paramount importance in the diagnostic management.
Several plasmatic biomarkers were tested to find an association with AFib. Perhaps the most studied ones were the natriuretic peptides that showed to be significantly increased in patients with AFib. Similarly, high sensitivity troponins are elevated in patients with the AFib. Another marker of left atrial stretching and also of ionotropic effects is apelin. Patients with lone AFib showed a significantly decreased levels of this peptide. Conflicting results were shown in studies with inflammatory biomarkers such as high sensitivity CRP Parameters reflecting thrombogenesis were also found to be associated with the arrhythmia. Fibrinogen and fibrin D-dimer were significantly increased in paroxysmal AFib. Finally, in the last years, the circulating micro RNAs emerged as a promising biomarker of AFib, having important function in suppression of messenger RNA responsible for thrombogenesis and ionotropic functions.
The weakness of the mentioned studies is, that the biomarkers were usually tested in patients with a few comorbidities. So, it is not known whether these biomarkers are specific for AFib "per se" or whether they just reflect pathophysiological mechanisms like inflammation, fibrogenesis or left atrium stretching that is also present in other cardiovascular diseases. Furthermore, the AFib cohorts were often not matched with the control groups adding more uncertainty. To clarify these questions, we designed a study where plasmatic biomarkers will be studied in high risk cohort of patients with AFib having several cardiovascular comorbidities. These patients will be subsequently matched with a control group according to the age, gender and the cardiovascular comorbidities.
Similarly, as the continuum of organic changes of the heart from the left ventricular diastolic dysfunction, left atrial dilatation ending with heart failure, there is also "arrhythmology continuum" in patients with arterial hypertension to supraventricular premature contractions via paroxysmal tachycardia of fibrillation up to the permanent atrial fibrillation (AFib). A common etiopathology factor of these disorders is increased sympathetic activity, which together with the catecholamine release during the stress causes arrhythmogenic substrates due to the atrial fibrogenesis. The relation between sleep disorders and the AFib is poorly understood. Micro awakenings during the night increases sympathetic activity and the arterial blood pressure. Other possible mechanism might be the decrease of plasmatic melatonin related to aging. Sleep disorders are linked to the increased heart rate, worsening of the heart rate variability, increased metabolism and body temperature, increased beta EEG activity and activation of the hypothalamic - pituitary - adrenal axis. In patients with arterial hypertension, there is an increased occurrence of premature atrial contractions that is linked to increased risk of AF incidence.
- Conditions
- Atrial Fibrillation
- Being tested
- ECHOcardiography, Peripheral blood samples for plasmatic biomarkers, Athens insomnia scale questionnaire, ECG Holter monitor, ECG event recorder
- Keywords
- Atrial fibrillation, ECG monitoring, quality of sleep, plasmatic biomarkers
- Medical subject headings
- Atrial Fibrillation, Sleep Initiation and Maintenance Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ECHOcardiographyDiagnostic test
ECHO parameters
- LA diameter
- LVEDD
- LVEF
- Diastolic dysfunction
- Valvular disease
Peripheral blood samples for plasmatic biomarkersDiagnostic test
- Coagulation
- D - dimer
- Fibrinogen
- Inflammation and fibrosis
- Hs - CRP
- AGEs
- Soluble RAGE
- Hemodynamics (LA stretch)
- Apelin
- NT - proBNP
- Hs - troponin
- MiRNA
- miRNA - 1
- miRNA - 133
- miRNA - 29b
- miRNA - 208a
- miRNA - 208b
- miRNA - 499
Athens insomnia scale questionnaireDiagnostic test
Athens insomnia scale questionnaire
ECG Holter monitorDiagnostic test
Patient receives ECG Holter monitor if included to the control group
ECG event recorderDiagnostic test
Patient receives ECG event recorder for twice daily (or if symptoms), 90 seconds duration ECG monitoring if included to the control group
| Study group | Role | What they receive |
|---|---|---|
| Study group | Adult patients with documented paroxysmal, nonvalvular atrial fibrillation with CHA2DS2-VASc score > 2 (for females > 3) and sinus rhythm at the time of inclusion. In total 100 patients will be included. Receives: Diagnostic Test: ECHOcardiography; Diagnostic Test: Peripheral blood samples for plasmatic biomarkers; Diagnostic Test: Athens insomnia scale questionnaire | |
| Control group | Patients without a history of palpitations or irregular heart rhythm. AFib will be excluded with the help of 7 days ECG Holter and ECG event recorder monitoring. In total 100 patients will be included.
Propensity matching according to the:
* CHA2DS2-VASc parameters
* LVEF: preserved (<40%), mid-range (40-49%) and reduced (>50%)
* Presence of diastolic dysfunction
* Glomerular filtration rate: (≥1,5 ml/s), (1,4-1 ml/s) and (0,9-0,5 ml/s)
* Drugs: ACE-I/ARB, betablockers, digoxin, amiodarone
* BMI: (<30kg/m2), (30-39kg/m2) and (≥40kg/m2)
* Smoking (>5 cigarettes per day) Receives: Diagnostic Test: ECHOcardiography; Diagnostic Test: Peripheral blood samples for plasmatic biomarkers; Diagnostic Test: Athens insomnia scale questionnaire; Diagnostic Test: ECG Holter monitor; Diagnostic Test: ECG event recorder |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasmatic biomarkers
Compare the plasmatic biomarkers between the cohort with and without atrial fibrillation:
- Coagulation a D - dimer b Fibrinogen
- Inflammation and fibrosis a Hs - CRP b AGEs c Soluble RAGE
- Hemodynamics (LA stretch) a Apelin b NT - proBNP c Hs - troponin
- MicroRNA a miRNA - 1 b miRNA - 19 c miRNA - 21 d miRNA - 124 e miRNA - 150 f miRNA - 328
Measured: Day of inclusion
Quality of sleep
Compare the quality of sleep between the cohort with and without atrial fibrillation by the means of Athens Insomnia Scale (AIS). It is measured by assessing eight factors amongst which first five factors are related to nocturnal sleep and last three factors are related to daytime dysfunction. These are rated on a 0-3 scale and the sleep is finally evaluated from the cumulative score of all factors and reported as an individual's sleep outcome. A cut-off score of ≥6 on the AIS is used to establish the diagnosis of insomnia.
Measured: Day of inclusion
Secondary outcomes (1)
Diagnostic plasmatic biomarker
Find sensitive and specific biomarker that could be used for the diagnostic management of atrial fibrillation:
- Coagulation a D - dimer b Fibrinogen
- Inflammation and fibrosis a Hs - CRP b AGEs c Soluble RAGE
- Hemodynamics (LA stretch) a Apelin b NT - proBNP c Hs - troponin
- MicroRNA a miRNA - 1 b miRNA - 19 c miRNA - 21 d miRNA - 124 e miRNA - 150 f miRNA - 328
Measured: Day of inclusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Feb 2019
- Study start11 Apr 2018
- Primary completion31 Dec 2019 (estimated)
- Study completion31 Dec 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Premedix Academy
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Allan Bohm, MD, Principal investigator, The National Institution of Cardiovascular DiseasesStefan Farsky, Associate professor, Principal investigator, Slovak league against hypertension
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03855540
- Sponsor's protocol ID
- 0012018
- Acronym
- AFISBIO
- Status last verified
- Mar 2019
- First submitted
- 5 Dec 2018
- Last updated
- 29 Mar 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- AFISBIO - Atrial Fibrillation in Relationship to Sleep Quality and Plasma Biomarkers.
- ClinicalTrials.gov ID
- NCT03855540
- Acronym / sponsor ID
- AFISBIO / 0012018
- Conditions
- Atrial Fibrillation
- Keywords
- Atrial fibrillation, ECG monitoring, quality of sleep, plasmatic biomarkers
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Premedix AcademyUniversity, hospital or other
- Study start
- 11 Apr 2018 (actual)
- Primary completion
- 31 Dec 2019 (estimated)
- Study completion
- 31 Dec 2019 (estimated)
- First posted
- 26 Feb 2019 (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.
- Compare the plasmatic biomarkers between the cohort with and without AFib.
- Find sensitive and specific biomarkers that could be used for the diagnostic management of AFib.
- Compare the quality of sleep between the cohort with and without AFib by the means of sleeping quality questionnaire
Detailed description
AFib is the most common sustained arrhythmia, associated with an increased risk of stroke, heart failure, and mortality. Despite the high prevalence, AFib may be asymptomatic and consequently subclinical. Detection of subclinical AFib is highly challenging as only a minority of the patients is diagnosed during a standard examinations with a 12 - lead ECG or a 24h ECG Holter monitoring. Documented AFib causes 15% of ischemic strokes, however approximately 25% of ischemic strokes is of an unknown etiology. It is believed that undetected subclinical AFib is responsible for these strokes. There is also evidence that asymptomatic AFib is associated with a higher incidence of strokes in comparison to symptomatic AFib.
Due to the fact that the standard ECG examination is not sufficient for AFib detection, various ECG screening methods have been introduced. Intermittent short ECG recording seems to be more effective than 24-hour Holter ECG in the detection of the arrhythmia however, it is not known whether it is superior to the 7 - day ECG Holter monitoring.
Plasmatic biomarkers might be of a paramount importance in the diagnostic management.
Several plasmatic biomarkers were tested to find an association with AFib. Perhaps the most studied ones were the natriuretic peptides that showed to be significantly increased in patients with AFib. Similarly, high sensitivity troponins are elevated in patients with the AFib. Another marker of left atrial stretching and also of ionotropic effects is apelin. Patients with lone AFib showed a significantly decreased levels of this peptide. Conflicting results were shown in studies with inflammatory biomarkers such as high sensitivity CRP Parameters reflecting thrombogenesis were also found to be associated with the arrhythmia. Fibrinogen and fibrin D-dimer were significantly increased in paroxysmal AFib. Finally, in the last years, the circulating micro RNAs emerged as a promising biomarker of AFib, having important function in suppression of messenger RNA responsible for thrombogenesis and ionotropic functions.
The weakness of the mentioned studies is, that the biomarkers were usually tested in patients with a few comorbidities. So, it is not known whether these biomarkers are specific for AFib "per se" or whether they just reflect pathophysiological mechanisms like inflammation, fibrogenesis or left atrium stretching that is also present in other cardiovascular diseases. Furthermore, the AFib cohorts were often not matched with the control groups adding more uncertainty. To clarify these questions, we designed a study where plasmatic biomarkers will be studied in high risk cohort of patients with AFib having several cardiovascular comorbidities. These patients will be subsequently matched with a control group according to the age, gender and the cardiovascular comorbidities.
Similarly, as the continuum of organic changes of the heart from the left ventricular diastolic dysfunction, left atrial dilatation ending with heart failure, there is also "arrhythmology continuum" in patients with arterial hypertension to supraventricular premature contractions via paroxysmal tachycardia of fibrillation up to the permanent atrial fibrillation (AFib). A common etiopathology factor of these disorders is increased sympathetic activity, which together with the catecholamine release during the stress causes arrhythmogenic substrates due to the atrial fibrogenesis. The relation between sleep disorders and the AFib is poorly understood. Micro awakenings during the night increases sympathetic activity and the arterial blood pressure. Other possible mechanism might be the decrease of plasmatic melatonin related to aging. Sleep disorders are linked to the increased heart rate, worsening of the heart rate variability, increased metabolism and body temperature, increased beta EEG activity and activation of the hypothalamic - pituitary - adrenal axis. In patients with arterial hypertension, there is an increased occurrence of premature atrial contractions that is linked to increased risk of AF incidence.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Study group | – | Diagnostic Test: ECHOcardiography, Diagnostic Test: Peripheral blood samples for plasmatic biomarkers, Diagnostic Test: Athens insomnia scale questionnaireAdult patients with documented paroxysmal, nonvalvular atrial fibrillation with CHA2DS2-VASc score > 2 (for females > 3) and sinus rhythm at the time of inclusion. In total 100 patients will be included. |
| Control group | – | Diagnostic Test: ECHOcardiography, Diagnostic Test: Peripheral blood samples for plasmatic biomarkers, Diagnostic Test: Athens insomnia scale questionnaire, Diagnostic Test: ECG Holter monitor, Diagnostic Test: ECG event recorderPatients without a history of palpitations or irregular heart rhythm. AFib will be excluded with the help of 7 days ECG Holter and ECG event recorder monitoring. In total 100 patients will be included. Propensity matching according to the: * CHA2DS2-VASc parameters * LVEF: preserved (<40%), mid-range (40-49%) and reduced (>50%) * Presence of diastolic dysfunction * Glomerular filtration rate: (≥1,5 ml/s), (1,4-1 ml/s) and (0,9-0,5 ml/s) * Drugs: ACE-I/ARB, betablockers, digoxin, amiodarone * BMI: (<30kg/m2), (30-39kg/m2) and (≥40kg/m2) * Smoking (>5 cigarettes per day) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Slovak hospitals and outpatients clinics
Key inclusion criteria (0 listed)
Key exclusion criteria (14 listed)
- Electrical cardioversion less than 7 days prior to inclusion
- Acute coronary syndrome less than 1 month prior to inclusion
- Cardiac surgery less than 3 months prior to inclusion
- Acute or decompensated heart failureat the time of inclusion
- Pregnancy
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 |
|---|---|---|
| ECHOcardiographyECHO parameters 1. LA diameter 2. LVEDD 3. LVEF 4. Diastolic dysfunction 5. Valvular disease | Diagnostic test | Control group, Study group |
| Peripheral blood samples for plasmatic biomarkers1. Coagulation * D - dimer * Fibrinogen 2. Inflammation and fibrosis * Hs - CRP * AGEs * Soluble RAGE 3. Hemodynamics (LA stretch) * Apelin * NT - proBNP * Hs - troponin 4. MiRNA * miRNA - 1 * miRNA - 133 * miRNA - 29b * miRNA - 208a * miRNA - 208b * miRNA - 499 | Diagnostic test | Control group, Study group |
| Athens insomnia scale questionnaireAthens insomnia scale questionnaire | Diagnostic test | Control group, Study group |
| ECG Holter monitorPatient receives ECG Holter monitor if included to the control group | Diagnostic test | Control group |
| ECG event recorderPatient receives ECG event recorder for twice daily (or if symptoms), 90 seconds duration ECG monitoring if included to the control group | Diagnostic test | Control group |
Primary outcome
Plasmatic biomarkers
Time frame: Day of inclusion
Compare the plasmatic biomarkers between the cohort with and without atrial fibrillation: 1. Coagulation a D - dimer b Fibrinogen 2. Inflammation and fibrosis a Hs - CRP b AGEs c Soluble RAGE 3. Hemodynamics (LA stretch) a Apelin b NT - proBNP c Hs - troponin 4. MicroRNA a miRNA - 1 b miRNA - 19 c miRNA - 21 d miRNA - 124 e miRNA - 150 f miRNA - 328
Quality of sleep
Time frame: Day of inclusion
Compare the quality of sleep between the cohort with and without atrial fibrillation by the means of Athens Insomnia Scale (AIS). It is measured by assessing eight factors amongst which first five factors are related to nocturnal sleep and last three factors are related to daytime dysfunction. These are rated on a 0-3 scale and the sleep is finally evaluated from the cumulative score of all factors and reported as an individual's sleep outcome. A cut-off score of ≥6 on the AIS is used to establish the diagnosis of insomnia.
1 secondary outcome
Diagnostic plasmatic biomarker
Time frame: Day of inclusion
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Mar 2019.
- Individual participant dataSharing planned: No
Related trials for Atrial Fibrillation
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
Active, not recruitingObservational study
Concomitant Left Atrial Appendage Closure and Pulsed Field Ablation-Asia
Concomitant Procedures, Atrial Fibrillation
Active, not recruiting
CONVERGE Post-Approval Study (PAS)
Chronic Atrial Fibrillation
Recruiting
Early Closure of Left Atrial Appendage for Patients With Atrial Fibrillation and Ischemic Stroke Despite Anticoagulation Therapy
Ischemic Stroke, Atrial Fibrillation
RecruitingPhase 2
Safety in Adult Participants With Atrial Fibrillation Who Are Treated With Anticoagulation
Atrial Fibrillation (AF)
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.
Allan Bohm, MD principal investigator
The National Institution of Cardiovascular Diseases
Stefan Farsky, Associate professor principal investigator
Slovak league against hypertension
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Atrial Fibrillation, run by Premedix Academy at 4 sites in Slovakia.
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 0 inclusion and 14 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 29 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Slovakia. 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.
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 Allan Bohm, MD (+421259320111, allan.bohm@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Plasmatic biomarkers (time frame: Day of inclusion). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 29 Mar 2019.