Trial Outcomes & Findings for Omega-3 Fatty Acids for Prevention of Post-Operative Atrial Fibrillation (NCT NCT00970489)

Last Updated: 2017-04-10

Results Overview

Primary: Occurrence of post-CS AF (atrial fibrillation or flutter) of at least 30 seconds duration and confirmed by rhythm strip or 12-lead ECG. This will include definite AF and probable AF (SVT likely to be AF depending on rate and other characteristics).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1516 participants

Primary outcome timeframe

up to 10 days post-surgery or discharge, whichever sooner

Results posted on

2017-04-10

Participant Flow

A total of 1,516 patients scheduled for cardiac surgery (CS) across 28 centers in the US, Italy, and Argentina, enrolled between Aug 2010 and Jun 2012. Inclusion criteria were broad; the main exclusions were regular use of fish oil or absence of sinus rhythm at enrollment. 48% of screened patients and 94% of eligible patients were enrolled.

Ineligible patients were most often excluded because they were not in sinus rhythm (40.5%), were on fish oil (28.9%), or were unwilling to provide informed consent (23.5%).

Participant milestones

Participant milestones
Measure	Olive Oil Capsule Placebo : Olive Oil capsules All patients were randomized to receive n-3 Polyunsaturated fatty acids (PUFA) or matched placebo in equal numbers using computer-generated numbers, stratified by medical center. Treatment: Either oral n-3 PUFA (1 g capsules, each containing \~850 mg of EPA+DHA) or matching placebo (olive oil, 1 g capsules). Total loading dose = 8 g over 2 to 4 days pre-op, followed by 2 g/d post-op until hospital discharge or until post-op day 10, whichever sooner.	Omega-3 Fatty Acid Capsules Omega -3 fatty acids : 10g dose of oral omega-3 fatty acid capsules over 3-5 days before surgery (or 8 g over 2 days before surgery), including the morning of surgery, followed by 2g/d after surgery for 10 days, or until discharge, whichever occurs first.
Overall Study STARTED	758	758
Overall Study COMPLETED	704	717
Overall Study NOT COMPLETED	54	41

Reasons for withdrawal

Reasons for withdrawal
Measure	Olive Oil Capsule Placebo : Olive Oil capsules All patients were randomized to receive n-3 Polyunsaturated fatty acids (PUFA) or matched placebo in equal numbers using computer-generated numbers, stratified by medical center. Treatment: Either oral n-3 PUFA (1 g capsules, each containing \~850 mg of EPA+DHA) or matching placebo (olive oil, 1 g capsules). Total loading dose = 8 g over 2 to 4 days pre-op, followed by 2 g/d post-op until hospital discharge or until post-op day 10, whichever sooner.	Omega-3 Fatty Acid Capsules Omega -3 fatty acids : 10g dose of oral omega-3 fatty acid capsules over 3-5 days before surgery (or 8 g over 2 days before surgery), including the morning of surgery, followed by 2g/d after surgery for 10 days, or until discharge, whichever occurs first.
Overall Study Death/Withdrew/Criteria Violation	54	41

Baseline Characteristics

Omega-3 Fatty Acids for Prevention of Post-Operative Atrial Fibrillation

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Olive Oil Capsule n=758 Participants Placebo : Olive Oil capsules	Omega-3 Fatty Acid Capsules n=758 Participants Omega -3 fatty acids : 10g dose of oral omega-3 fatty acid capsules over 3-5 days before surgery (or 8 g over 2 days before surgery), including the morning of surgery, followed by 2g/d after surgery for 10 days, or until discharge, whichever occurs first.	Total n=1516 Participants Total of all reporting groups
Age, Continuous	63.6 years STANDARD_DEVIATION 12.4 • n=5 Participants	63.8 years STANDARD_DEVIATION 12.6 • n=7 Participants	63.7 years STANDARD_DEVIATION 12.5 • n=5 Participants
Sex: Female, Male Female	215 Participants n=5 Participants	207 Participants n=7 Participants	422 Participants n=5 Participants
Sex: Female, Male Male	543 Participants n=5 Participants	551 Participants n=7 Participants	1094 Participants n=5 Participants

PRIMARY outcome

Timeframe: up to 10 days post-surgery or discharge, whichever sooner

Outcome measures

Outcome measures
Measure	Olive Oil Capsule n=758 Participants Placebo : Olive Oil capsules	Omega-3 Fatty Acid Capsules n=758 Participants Omega -3 fatty acids : 10g dose of oral omega-3 fatty acid capsules over 3-5 days before surgery (or 8 g over 2 days before surgery), including the morning of surgery, followed by 2g/d after surgery for 10 days, or until discharge, whichever occurs first.
Any First Post-op Atrial Fibrillation or Flutter (AF)	233 Participants	227 Participants

SECONDARY outcome

Timeframe: up to 10 days post-surgery or discharge, whichever sooner

Secondary AF endpoints included post-op AF that was sustained (\>1 hour), symptomatic, or treated with pharmacological or electrical cardioversion; post-op AF excluding atrial flutter; time to first post-op AF; and the number of post-op AF episodes per patient. OPERA also evaluated the total number of in-hospital days in which any post-op AF, including sustained post-op AF, was present; and the proportion of in-hospital days free of any post-op AF. All potential episodes of post-op AF and other tachyarrhythmias were reviewed and adjudicated by a centralized Events Committee of cardiac electrophysiologists. Additional endpoints included resource utilization, major adverse cardiovascular events (MACE), arterial thromboembolism, and 30-day mortality.

Outcome measures

Outcome measures
Measure	Olive Oil Capsule n=758 Participants Placebo : Olive Oil capsules	Omega-3 Fatty Acid Capsules n=758 Participants Omega -3 fatty acids : 10g dose of oral omega-3 fatty acid capsules over 3-5 days before surgery (or 8 g over 2 days before surgery), including the morning of surgery, followed by 2g/d after surgery for 10 days, or until discharge, whichever occurs first.
Post-op Af Sustained, symptomatic, or treated post-op AF	231 Participants	224 Participants
Post-op Af Post-op AF excluding flutter	220 Participants	217 Participants

SECONDARY outcome

Timeframe: up to 10 days post-surgery or discharge, whichever sooner

* The first 3 suspected episodes of atrial fibrillation or flutter of at least 30 sec duration following randomization were documented, including the following information: * Printed or digital rhythm strip and/or 12-lead ECG. * Recording of time of onset and time of cessation. * Additional documentation of temporally associated signs of symptoms, such as new or worsening chest pain, shortness of breath, or lightheadedness; drop in blood pressure requiring escalation of fluid or pressor treatment; or need for electrical or pharmacologic cardioversion. * The first suspected episode of each of other supraventricular or unknown narrow-complex tachycardia of at least 30 sec duration following randomization was also documented.

Outcome measures

Outcome measures
Measure	Olive Oil Capsule n=758 Participants Placebo : Olive Oil capsules	Omega-3 Fatty Acid Capsules n=758 Participants Omega -3 fatty acids : 10g dose of oral omega-3 fatty acid capsules over 3-5 days before surgery (or 8 g over 2 days before surgery), including the morning of surgery, followed by 2g/d after surgery for 10 days, or until discharge, whichever occurs first.
Other Arrhythmias Other supraventricular tachycardia	6 Participants	11 Participants
Other Arrhythmias Ventricular tachycardia or fibrillation	9 Participants	5 Participants

SECONDARY outcome

Timeframe: up to 10 days post-surgery or discharge, whichever sooner

1. Number of days in the ICU, of telemetry monitoring, and of total hospital stay. 2. Non-AF arrhythmias of at least 30 sec duration, including non-AF-SVT, ventricular tachycardia (VT), and ventricular flutter (VF), assessed and adjudicated by the Events Committee. 3. MACE: Combined total mortality, myocardial infarction, and stroke. 4. Bleeding, assessed by (a) chest tube output in the 24 hour period following surgery and (b) total number of packed red blood cell (RBC) transfusions from enrollment to end of treatment (hospital discharge or post-op day 10). 5. Significant adverse events: Discontinuation of study treatment, at the discretion of the treating physicians, for suspected significant allergic reaction, severe gastrointestinal intolerance, significant bleeding, or other side effects requiring discontinuation. 6. Thirty-day mortality assessed 7. One-year mortality assessed

Outcome measures

Outcome measures
Measure	Olive Oil Capsule n=758 Participants Placebo : Olive Oil capsules	Omega-3 Fatty Acid Capsules n=758 Participants Omega -3 fatty acids : 10g dose of oral omega-3 fatty acid capsules over 3-5 days before surgery (or 8 g over 2 days before surgery), including the morning of surgery, followed by 2g/d after surgery for 10 days, or until discharge, whichever occurs first.
Other Endpoints MACE, in-hospital	20 Participants	13 Participants
Other Endpoints Total mortality, 30 days	15 Participants	8 Participants

Adverse Events

Olive Oil Capsule

Serious events: 147 serious events

Other events: 20 other events

Deaths: 0 deaths

Omega-3 Fatty Acid Capsules

Serious events: 136 serious events

Other events: 19 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Olive Oil Capsule n=758 participants at risk Placebo : Olive Oil capsules	Omega-3 Fatty Acid Capsules n=758 participants at risk Omega -3 fatty acids : 10g dose of oral omega-3 fatty acid capsules over 3-5 days before surgery (or 8 g over 2 days before surgery), including the morning of surgery, followed by 2g/d after surgery for 10 days, or until discharge, whichever occurs first.
Blood and lymphatic system disorders Bleeding	4.7% 36/758 • Number of events 36	4.0% 30/758 • Number of events 32
Blood and lymphatic system disorders Bone marrow or coalgulation	0.00% 0/758	0.79% 6/758 • Number of events 6
Cardiac disorders Cardiac	7.1% 54/758 • Number of events 60	5.8% 44/758 • Number of events 50
General disorders Constitutional symptoms	1.2% 9/758 • Number of events 9	1.3% 10/758 • Number of events 10
Musculoskeletal and connective tissue disorders Dermatology or musculoskeletal	0.13% 1/758 • Number of events 1	0.40% 3/758 • Number of events 3
Gastrointestinal disorders Gastrointestinal, hepatobiliary, or pancreas	0.53% 4/758 • Number of events 4	1.1% 8/758 • Number of events 8
Immune system disorders Infection	3.4% 26/758 • Number of events 27	2.1% 16/758 • Number of events 16
Metabolism and nutrition disorders Metabolic or laboratory	0.13% 1/758 • Number of events 1	0.13% 1/758 • Number of events 2
Nervous system disorders Neurologic	2.0% 15/758 • Number of events 17	1.3% 10/758 • Number of events 10
Respiratory, thoracic and mediastinal disorders Pulmonary	3.0% 23/758 • Number of events 25	2.4% 18/758 • Number of events 18
Renal and urinary disorders Renal or genitourinary	0.79% 6/758 • Number of events 6	0.79% 6/758 • Number of events 6
Vascular disorders Vascular	0.40% 3/758 • Number of events 4	0.66% 5/758 • Number of events 5
General disorders Other	0.79% 6/758 • Number of events 6	0.53% 4/758 • Number of events 4

Other adverse events

Other adverse events
Measure	Olive Oil Capsule n=758 participants at risk Placebo : Olive Oil capsules	Omega-3 Fatty Acid Capsules n=758 participants at risk Omega -3 fatty acids : 10g dose of oral omega-3 fatty acid capsules over 3-5 days before surgery (or 8 g over 2 days before surgery), including the morning of surgery, followed by 2g/d after surgery for 10 days, or until discharge, whichever occurs first.
Blood and lymphatic system disorders Bone marrow or coagulation	0.00% 0/758	0.00% 0/758
Blood and lymphatic system disorders Bleeding	0.92% 7/758 • Number of events 7	0.26% 2/758 • Number of events 2
Cardiac disorders Cardiac	0.40% 3/758 • Number of events 3	0.79% 6/758 • Number of events 6
General disorders Constitutional symptoms	0.13% 1/758 • Number of events 1	0.00% 0/758
Musculoskeletal and connective tissue disorders Dermatology or musculoskeletal	0.00% 0/758	0.00% 0/758
Gastrointestinal disorders Gastrointestinal, hepatobiliary, or pancreas	0.26% 2/758 • Number of events 2	1.1% 8/758 • Number of events 8
Immune system disorders Infection	0.13% 1/758 • Number of events 1	0.13% 1/758 • Number of events 1
Metabolism and nutrition disorders Metabolic or laboratory	0.00% 0/758	0.00% 0/758
Nervous system disorders Neurologic	0.66% 5/758 • Number of events 5	0.13% 1/758 • Number of events 1
Respiratory, thoracic and mediastinal disorders Pulmonary	0.40% 3/758 • Number of events 3	0.13% 1/758 • Number of events 1
Renal and urinary disorders Renal or genitourinary	0.13% 1/758 • Number of events 1	0.00% 0/758
Vascular disorders Vascular	0.13% 1/758 • Number of events 1	0.00% 0/758
General disorders Other	0.00% 0/758	0.00% 0/758

Additional Information

Namasha Schelling

Harvard School of Public Health

Phone: 617-432-1734

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place