Primary objective:Investigate the efficacy and safety of Vernakalant in the acute conversion of AF, as compared to Amiodarone and rate control alone, in critically ill patients admitted to the medical and non-cardiac surgical ICU.Secondary objective…
ID
Source
Brief title
Condition
- Cardiac arrhythmias
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary endpoint:
Proportion of critically ill patients admitted to the medical and non-cardiac
surgical ICU demonstrating conversion to sinus rhythm (SR) from AF within 90
minutes of first exposure to the study drug.
Secondary outcome
Secondary endpoint:
Association between stress hormonal markers and onset of AF in critically ill
patients admitted to the medical ICU in a maximal period of one week after
admission.
Tertiary endpoints:
- Correlation between success rate of pharmacologic conversion and stress
hormone levels
- All cause mortality in the 3 treatment groups
- All cause mortality comparing rhythm control to rate control
- Duration of hospitalization comparing rhythm control to rate control
- Frequency of acute cerebral or peripheral ischemic events comparing rhythm
control to rate control
- Proportion of critically ill patients admitted to the medical and non-cardiac
surgical ICU maintaining SR after successful initial conversion at 24 hours.
- Safety endpoints:
* Systolic bloodpressure drop below 80 mmHg
* Disturbances in AV conduction
* New complex ventricular arrhythmia
* Allergic reaction
* Chest pain
* Prolongation of QTc (>550ms) compared to baseline
Background summary
AF is a supra-ventricular arrhythmia characterized by complete disarray of
electric activity of the atria, resulting in their hemodynamically ineffective
fibrillating motion and absolute (tachy)arrhythmic contractions of the
ventricles. It is plausible that the impact of AF on patients suffering from
critical illness may be even more severe than in the general clinical or
outpatient population given the fact that during critical illness the body
operates often on the edge of its capabilities. However, to which extent AF
itself contributes to these differences, however, is still a matter of debate.
In patients without critical illness there is plenty of evidence, provided by
randomized clinical trials, proving against the superiority of rhythm control
above rate control, having lead thereby to fundamental changes in clinical
practice. In the ICU setting, however, current clinical practice is still based
on retrospective data and expert opinion resulting from the lack convincing
evidence.
The fact that AF complicates critical illness in 5-40% depending on its
etiology justifies the efforts to answer these fundamental questions.
Therefore, prospective randomized trials are necessary to answer these
questions and fill in the blanks of adequate management of AF in the ICU.
Study objective
Primary objective:
Investigate the efficacy and safety of Vernakalant in the acute conversion of
AF, as compared to Amiodarone and rate control alone, in critically ill
patients admitted to the medical and non-cardiac surgical ICU.
Secondary objective:
To assess the correlation between stress hormone levels, where appropriate, and
the onset of AF in critically ill patients admitted to the medical ICU.
Tertiary objectives:
• To assess the correlation between success rate of pharmacologic conversion of
AF and various stress hormone levels in critically ill patients admitted to the
medical and non-cardiac surgical ICU.
• To compare all cause in-hospital mortality between critically ill patients
admitted to the medical and non-cardiac surgical ICU treated with Vernakalant,
Amiodarone or rate control medication.
• To compare all cause in-hospital mortality between critically ill patients
admitted to the medical and non-cardiac surgical ICU treated with Vernakalant
or Amiodarone considered as one group of rhythm control against rate control
medication.
• To compare the duration of hospitalization between critically ill patients
admitted to the medical and non-cardiac surgical ICU treated with Vernakalant
or Amiodarone considered as one group of rhythm control against rate control
medication.
• To compare the frequency of acute cerebral of peripheral ischemic events
between critically ill patients admitted to the medical and non-cardiac
surgical ICU treated with Vernakalant or Amiodarone, considered as one group
of rhythm control, against rate control medication.
•To compare the time to conversion within 90 minutes between the various groups
of patients with critical illness admitted to the medical and non-cardiac
surgical ICU.
Safety objective:
To compare the frequency and severity of serious adverse events (SAE) between
critically ill patients admitted to the medical and non-cardiac surgical ICU
treated with Vernakalant, Amiodarone and rate control medication.
Study design
This multi center study will be carried out in the Isala hospital (Zwolle), the
MUMC (Maastricht) and the Radboudumc (Nijmegen) in the Netherlands. The study
itself comprises two consecutive, but, independent parts:
- Part A: prospective cohort study
- Part B: randomized clinical trial
Preferentially, patients will be included in both Part A and B, however, they
may be included only in Part B if not found eligible for Part A.
Intervention
Part A: no intervention
Part B: the study patients will be randomized 1:1:1 to:
- Vernakalant
- Amiodarone
- Rate control
Study burden and risks
Vernakalant appears to be safe and has less side effects. Possible life
threatening side effects like serious arrhythmias only appeared in patients
with serious cardiac diseases. In this study all patients will be screened on
these serious cardiac diseases, unless recent research was performed on these
diseases.
The most prevalent side effects of Vernakalant from previous trials are strange
taste in the mouth, tingling of arms and feet, nausea, coughing and
hypotension.
Dokter van Heesweg 2
Zwolle 8025AB
NL
Dokter van Heesweg 2
Zwolle 8025AB
NL
Listed location countries
Age
Inclusion criteria
Inclusion criteria Part A:
• Admission to medical ICU
• Age >= 18 years
• Providing informed consent (if necessary by legally acceptable representative)
• Expected duration of admission > 48 h;Additional inclusion criteria Part B:
• Admission to medical or non-cardiac surgical ICU
• Age >= 18 years
• Providing informed consent (if necessary by legally acceptable representative)
• Expected duration of admission > 48 h
• New onset AF<3 hr
Exclusion criteria
Exclusion criteria Part A (any of the following):
• AF on admission
• Inability to collect blood samples or 24 hour urine
• Major structural cardiac disease as revealed by transthoracic echocardiography (TTE)
• Administration of corticosteroids during or prior to admission
• Any disease affecting corticosteroid, renine, aldosterone or catecholamine hormone production (eg.: Cushing-, Addisone-, Conn disease, Reninoma, Pheochromocytoma);Exclusion criteria Part B (any of the following):
• AF on admission
• Hemodynamically unstable AF (systolic RR<90 mmHg or signs of systemic hypoperfusion)
• Atrial Flutter (Afl)
• Conversion to sinus rhythm before randomization
• Major structural cardiac disease as revealed by TTE
• Contraindication against Vernakalant
• Contraindication against Amiodarone
• Acute coronary syndrome (ACS)
• Acute decompensated heart failure
• Major, incorrigible electrolyte disturbances
• Administration of Amiodarone within 3 months prior to inclusion
• Being under active anti-arrhythmic treatment, other than conventional beta-blocker or digoxine
• Pregnancy or breast feeding,
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2013-004442-42-NL |
| CCMO | NL46690.075.13 |
| OMON | NL-OMON20722 |