Trial Outcomes & Findings for Ranolazine in Atrial Fibrillation Following An ELectricaL CardiOversion (NCT NCT01534962)
NCT ID: NCT01534962
Last Updated: 2014-08-19
Results Overview
Time to first AF recurrence reported by patient-reported TT-ECG or 12-Lead ECG at the study site, whichever occurred first. Patients discontinuing the study without AF were censored at the time of the last available ECG.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
241 participants
Primary outcome timeframe
16 weeks (112 days)
Results posted on
2014-08-19
Participant Flow
A total of 310 patients were screened and underwent cardioversion (CV). Of these, 241 were still in sinus rhythm 2 hours post-CV and, thus, were eligible for randomization. Patients who experienced an atrial fibrillation (AF) recurrence could continue the study if no medical intervention was needed and otherwise had to discontinue the study.
Participant milestones
| Measure |
Ranolazine Low Dose
Ranolazine, low dose, oral, BID
Ranolazine: Oral administration, BID; for a maximum of 112 days.
|
Ranolazine Intermediate Dose
Ranolazine, intermediate dose, oral, BID
Ranolazine: Oral administration, BID; for a maximum of 112 days.
|
Ranolazin High Dose
Ranolazine, high dose, oral, BID
Ranolazine: Oral administration, BID; for a maximum of 112 days.
|
Placebo
Placebo (sugar pill), oral, BID.
Placebo: Oral administration, BID; for a maximum of 112 days.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
67
|
60
|
58
|
56
|
|
Overall Study
COMPLETED
|
30
|
34
|
34
|
24
|
|
Overall Study
NOT COMPLETED
|
37
|
26
|
24
|
32
|
Reasons for withdrawal
| Measure |
Ranolazine Low Dose
Ranolazine, low dose, oral, BID
Ranolazine: Oral administration, BID; for a maximum of 112 days.
|
Ranolazine Intermediate Dose
Ranolazine, intermediate dose, oral, BID
Ranolazine: Oral administration, BID; for a maximum of 112 days.
|
Ranolazin High Dose
Ranolazine, high dose, oral, BID
Ranolazine: Oral administration, BID; for a maximum of 112 days.
|
Placebo
Placebo (sugar pill), oral, BID.
Placebo: Oral administration, BID; for a maximum of 112 days.
|
|---|---|---|---|---|
|
Overall Study
Randomized but did not start treatment
|
2
|
0
|
0
|
1
|
|
Overall Study
Discontinued at AF recurrence
|
35
|
26
|
24
|
31
|
Baseline Characteristics
Ranolazine in Atrial Fibrillation Following An ELectricaL CardiOversion
Baseline characteristics by cohort
| Measure |
Ranolazine Low Dose
n=65 Participants
Ranolazine, low dose, oral, BID
|
Ranolazine Intermediate Dose
n=60 Participants
Ranolazine, intermediate dose, oral, BID
|
Ranolazin High Dose
n=58 Participants
Ranolazine, high dose, oral, BID
|
Placebo
n=55 Participants
Placebo, oral, BID.
|
Total
n=238 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
66.9 years
STANDARD_DEVIATION 11.8 • n=5 Participants
|
65.5 years
STANDARD_DEVIATION 8.5 • n=7 Participants
|
63.6 years
STANDARD_DEVIATION 11.3 • n=5 Participants
|
65.2 years
STANDARD_DEVIATION 9.5 • n=4 Participants
|
65.3 years
STANDARD_DEVIATION 10.4 • n=21 Participants
|
|
Sex: Female, Male
Female
|
19 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
14 Participants
n=4 Participants
|
54 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
46 Participants
n=5 Participants
|
51 Participants
n=7 Participants
|
46 Participants
n=5 Participants
|
41 Participants
n=4 Participants
|
184 Participants
n=21 Participants
|
|
Time since AF diagnosis
|
10.5 months
STANDARD_DEVIATION 24.0 • n=5 Participants
|
7.2 months
STANDARD_DEVIATION 12.9 • n=7 Participants
|
15.5 months
STANDARD_DEVIATION 28.2 • n=5 Participants
|
6.9 months
STANDARD_DEVIATION 13.5 • n=4 Participants
|
10.0 months
STANDARD_DEVIATION 20.7 • n=21 Participants
|
PRIMARY outcome
Timeframe: 16 weeks (112 days)Population: Intention-to-treat-approach that analyzed all randomised patients who took at least one dose of study medication (N=238, i.e. excluding 3 randomized patients).
Time to first AF recurrence reported by patient-reported TT-ECG or 12-Lead ECG at the study site, whichever occurred first. Patients discontinuing the study without AF were censored at the time of the last available ECG.
Outcome measures
| Measure |
Ranolazine Low Dose
n=65 Participants
Ranolazine, low dose, oral, BID
Ranolazine: Oral administration, BID; for a maximum of 112 days.
|
Ranolazine Intermediate Dose
n=60 Participants
Ranolazine, intermediate dose, oral, BID
Ranolazine: Oral administration, BID; for a maximum of 112 days.
|
Ranolazin High Dose
n=58 Participants
Ranolazine, high dose, oral, BID
Ranolazine: Oral administration, BID; for a maximum of 112 days.
|
Placebo
n=55 Participants
Placebo (sugar pill), oral, BID.
Placebo: Oral administration, BID; for a maximum of 112 days.
|
|---|---|---|---|---|
|
Time From Randomization to First Documented AF Recurrence.
|
51.0 Days
Interval 9.0 to
The upper limit of the CI was not calculable.
|
NA Days
Interval 68.0 to
The Kaplan-Meier estimate of the median was not calculable
|
117.0 Days
Interval 17.0 to
The upper limit of the CI was not calculable.
|
58.0 Days
Interval 16.0 to
The upper limit of the CI was not calculable.
|
SECONDARY outcome
Timeframe: 16 weeks (112 days)Population: Intention-to-Treat (N=238)
Outcome measures
| Measure |
Ranolazine Low Dose
n=65 Participants
Ranolazine, low dose, oral, BID
Ranolazine: Oral administration, BID; for a maximum of 112 days.
|
Ranolazine Intermediate Dose
n=60 Participants
Ranolazine, intermediate dose, oral, BID
Ranolazine: Oral administration, BID; for a maximum of 112 days.
|
Ranolazin High Dose
n=58 Participants
Ranolazine, high dose, oral, BID
Ranolazine: Oral administration, BID; for a maximum of 112 days.
|
Placebo
n=55 Participants
Placebo (sugar pill), oral, BID.
Placebo: Oral administration, BID; for a maximum of 112 days.
|
|---|---|---|---|---|
|
Number of Patients With Documented AF Recurrences
|
37 participants
|
25 participants
|
23 participants
|
31 participants
|
SECONDARY outcome
Timeframe: 16 weeks (112 days)Population: Intention-to-Treat (N=238)
A confirmed AF recurrence was defined as a documented AF recurrence which was confirmed by a consecutive ECG performed at least 1 hour after first AF documentation.
Outcome measures
| Measure |
Ranolazine Low Dose
n=65 Participants
Ranolazine, low dose, oral, BID
Ranolazine: Oral administration, BID; for a maximum of 112 days.
|
Ranolazine Intermediate Dose
n=60 Participants
Ranolazine, intermediate dose, oral, BID
Ranolazine: Oral administration, BID; for a maximum of 112 days.
|
Ranolazin High Dose
n=58 Participants
Ranolazine, high dose, oral, BID
Ranolazine: Oral administration, BID; for a maximum of 112 days.
|
Placebo
n=55 Participants
Placebo (sugar pill), oral, BID.
Placebo: Oral administration, BID; for a maximum of 112 days.
|
|---|---|---|---|---|
|
Time From Randomization to First Documented and Confirmed AF Recurrence
|
73.0 Days
Interval 11.0 to
The upper limit of the 95% CI was not calculable.
|
NA Days
The Kaplan-Meier estimate of the median and the lower/upper limit of the 95% CI was not calculable.
|
NA Days
Interval 117.0 to
The Kaplan-Meier estimate of the median and the upper limit of the 95% CI was not calculable.
|
NA Days
Interval 38.0 to
The Kaplan-Meier estimate of the median and the upper limit of the 95% CI was not calculable.
|
SECONDARY outcome
Timeframe: 16 weeks (112 days)Population: Intention-to-Treat
Outcome measures
| Measure |
Ranolazine Low Dose
n=65 Participants
Ranolazine, low dose, oral, BID
Ranolazine: Oral administration, BID; for a maximum of 112 days.
|
Ranolazine Intermediate Dose
n=60 Participants
Ranolazine, intermediate dose, oral, BID
Ranolazine: Oral administration, BID; for a maximum of 112 days.
|
Ranolazin High Dose
n=58 Participants
Ranolazine, high dose, oral, BID
Ranolazine: Oral administration, BID; for a maximum of 112 days.
|
Placebo
n=55 Participants
Placebo (sugar pill), oral, BID.
Placebo: Oral administration, BID; for a maximum of 112 days.
|
|---|---|---|---|---|
|
Number of Patients With Documented and Confirmed AF Recurrences
|
31 participants
|
19 participants
|
16 participants
|
24 participants
|
SECONDARY outcome
Timeframe: 16 weeks (112 days)Population: Modified Intention-to-Treat Population (N=217) excluding 21 patients with AF relapse within 48 hours post cardioversion
Excluding patients with early relapses (within 48 hours) while the study drug, started after cardioversion, had not yet reached steady-state.
Outcome measures
| Measure |
Ranolazine Low Dose
n=60 Participants
Ranolazine, low dose, oral, BID
Ranolazine: Oral administration, BID; for a maximum of 112 days.
|
Ranolazine Intermediate Dose
n=54 Participants
Ranolazine, intermediate dose, oral, BID
Ranolazine: Oral administration, BID; for a maximum of 112 days.
|
Ranolazin High Dose
n=54 Participants
Ranolazine, high dose, oral, BID
Ranolazine: Oral administration, BID; for a maximum of 112 days.
|
Placebo
n=49 Participants
Placebo (sugar pill), oral, BID.
Placebo: Oral administration, BID; for a maximum of 112 days.
|
|---|---|---|---|---|
|
Time From Randomization to First Documented AF Recurrence in Patients With Sinus Rhythm 48 Hours After Cardioversion
|
56.0 Days
Interval 11.0 to
The upper limit of the 95% CI was not calculable.
|
NA Days
Interval 98.0 to
The Kaplan-Meier estimate of the median and the upper limit of the 95% CI was not calculable.
|
117.0 Days
Interval 18.0 to
The upper limit of the 95% CI was not calculable.
|
78.0 Days
Interval 37.0 to
The upper limit of the 95% CI was not calculable.
|
SECONDARY outcome
Timeframe: 16 weeks (112 days)Population: Modified Intention-to-Treat Population (N=217) excluding 21 patients with AF relapse within 48 hours post cardioversion
Documented AF recurrences in those patients who did not experience early relapses (within 48 hours after cardioversion)
Outcome measures
| Measure |
Ranolazine Low Dose
n=60 Participants
Ranolazine, low dose, oral, BID
Ranolazine: Oral administration, BID; for a maximum of 112 days.
|
Ranolazine Intermediate Dose
n=54 Participants
Ranolazine, intermediate dose, oral, BID
Ranolazine: Oral administration, BID; for a maximum of 112 days.
|
Ranolazin High Dose
n=54 Participants
Ranolazine, high dose, oral, BID
Ranolazine: Oral administration, BID; for a maximum of 112 days.
|
Placebo
n=49 Participants
Placebo (sugar pill), oral, BID.
Placebo: Oral administration, BID; for a maximum of 112 days.
|
|---|---|---|---|---|
|
Number of Patients in Sinus Rhythm 48 Hours After Cardioversion With Documented AF Recurrence
|
32 participants
|
19 participants
|
21 participants
|
27 participants
|
Adverse Events
Ranolazine Low Dose
Serious events: 2 serious events
Other events: 51 other events
Deaths: 0 deaths
Ranolazine Intermediate Dose
Serious events: 3 serious events
Other events: 46 other events
Deaths: 0 deaths
Ranolazin High Dose
Serious events: 3 serious events
Other events: 42 other events
Deaths: 0 deaths
Placebo
Serious events: 4 serious events
Other events: 41 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Ranolazine Low Dose
n=65 participants at risk
Ranolazine, low dose, oral, BID
Ranolazine: Oral administration, BID; for a maximum of 112 days.
|
Ranolazine Intermediate Dose
n=60 participants at risk
Ranolazine, intermediate dose, oral, BID
Ranolazine: Oral administration, BID; for a maximum of 112 days.
|
Ranolazin High Dose
n=58 participants at risk
Ranolazine, high dose, oral, BID
Ranolazine: Oral administration, BID; for a maximum of 112 days.
|
Placebo
n=55 participants at risk
Placebo (sugar pill), oral, BID.
Placebo: Oral administration, BID; for a maximum of 112 days.
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Pancreatitis
|
1.5%
1/65 • Number of events 1 • 16 weeks (112 days)
|
0.00%
0/60 • 16 weeks (112 days)
|
0.00%
0/58 • 16 weeks (112 days)
|
0.00%
0/55 • 16 weeks (112 days)
|
|
Hepatobiliary disorders
Hepatitis
|
1.5%
1/65 • Number of events 1 • 16 weeks (112 days)
|
0.00%
0/60 • 16 weeks (112 days)
|
0.00%
0/58 • 16 weeks (112 days)
|
0.00%
0/55 • 16 weeks (112 days)
|
|
Cardiac disorders
Acute Coronary Syndrome
|
0.00%
0/65 • 16 weeks (112 days)
|
1.7%
1/60 • Number of events 1 • 16 weeks (112 days)
|
0.00%
0/58 • 16 weeks (112 days)
|
0.00%
0/55 • 16 weeks (112 days)
|
|
Cardiac disorders
Angina Pectoris
|
0.00%
0/65 • 16 weeks (112 days)
|
1.7%
1/60 • Number of events 1 • 16 weeks (112 days)
|
0.00%
0/58 • 16 weeks (112 days)
|
1.8%
1/55 • Number of events 1 • 16 weeks (112 days)
|
|
Cardiac disorders
Angina unstable
|
0.00%
0/65 • 16 weeks (112 days)
|
1.7%
1/60 • Number of events 1 • 16 weeks (112 days)
|
0.00%
0/58 • 16 weeks (112 days)
|
0.00%
0/55 • 16 weeks (112 days)
|
|
Cardiac disorders
Atrial Fibrillation
|
0.00%
0/65 • 16 weeks (112 days)
|
0.00%
0/60 • 16 weeks (112 days)
|
0.00%
0/58 • 16 weeks (112 days)
|
1.8%
1/55 • Number of events 1 • 16 weeks (112 days)
|
|
Cardiac disorders
Atrial Flutter
|
0.00%
0/65 • 16 weeks (112 days)
|
0.00%
0/60 • 16 weeks (112 days)
|
1.7%
1/58 • Number of events 1 • 16 weeks (112 days)
|
0.00%
0/55 • 16 weeks (112 days)
|
|
Cardiac disorders
Coronary Artery Disease
|
0.00%
0/65 • 16 weeks (112 days)
|
1.7%
1/60 • Number of events 1 • 16 weeks (112 days)
|
0.00%
0/58 • 16 weeks (112 days)
|
0.00%
0/55 • 16 weeks (112 days)
|
|
Cardiac disorders
Sick Sinus Syndrome
|
0.00%
0/65 • 16 weeks (112 days)
|
0.00%
0/60 • 16 weeks (112 days)
|
0.00%
0/58 • 16 weeks (112 days)
|
1.8%
1/55 • Number of events 1 • 16 weeks (112 days)
|
|
Cardiac disorders
Ventricular Tachycardia
|
0.00%
0/65 • 16 weeks (112 days)
|
0.00%
0/60 • 16 weeks (112 days)
|
0.00%
0/58 • 16 weeks (112 days)
|
1.8%
1/55 • Number of events 1 • 16 weeks (112 days)
|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/65 • 16 weeks (112 days)
|
0.00%
0/60 • 16 weeks (112 days)
|
1.7%
1/58 • Number of events 1 • 16 weeks (112 days)
|
0.00%
0/55 • 16 weeks (112 days)
|
|
General disorders
Sudden Death
|
0.00%
0/65 • 16 weeks (112 days)
|
0.00%
0/60 • 16 weeks (112 days)
|
0.00%
0/58 • 16 weeks (112 days)
|
1.8%
1/55 • Number of events 1 • 16 weeks (112 days)
|
|
Nervous system disorders
Syncope
|
0.00%
0/65 • 16 weeks (112 days)
|
0.00%
0/60 • 16 weeks (112 days)
|
1.7%
1/58 • Number of events 1 • 16 weeks (112 days)
|
0.00%
0/55 • 16 weeks (112 days)
|
|
Psychiatric disorders
Psychotic Disorder
|
0.00%
0/65 • 16 weeks (112 days)
|
1.7%
1/60 • Number of events 1 • 16 weeks (112 days)
|
0.00%
0/58 • 16 weeks (112 days)
|
0.00%
0/55 • 16 weeks (112 days)
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/65 • 16 weeks (112 days)
|
1.7%
1/60 • Number of events 1 • 16 weeks (112 days)
|
0.00%
0/58 • 16 weeks (112 days)
|
0.00%
0/55 • 16 weeks (112 days)
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/65 • 16 weeks (112 days)
|
0.00%
0/60 • 16 weeks (112 days)
|
1.7%
1/58 • Number of events 1 • 16 weeks (112 days)
|
0.00%
0/55 • 16 weeks (112 days)
|
|
Vascular disorders
Hypertension
|
1.5%
1/65 • Number of events 1 • 16 weeks (112 days)
|
0.00%
0/60 • 16 weeks (112 days)
|
0.00%
0/58 • 16 weeks (112 days)
|
1.8%
1/55 • Number of events 1 • 16 weeks (112 days)
|
|
Vascular disorders
Orthostatic Hypotension
|
0.00%
0/65 • 16 weeks (112 days)
|
0.00%
0/60 • 16 weeks (112 days)
|
1.7%
1/58 • Number of events 1 • 16 weeks (112 days)
|
0.00%
0/55 • 16 weeks (112 days)
|
Other adverse events
| Measure |
Ranolazine Low Dose
n=65 participants at risk
Ranolazine, low dose, oral, BID
Ranolazine: Oral administration, BID; for a maximum of 112 days.
|
Ranolazine Intermediate Dose
n=60 participants at risk
Ranolazine, intermediate dose, oral, BID
Ranolazine: Oral administration, BID; for a maximum of 112 days.
|
Ranolazin High Dose
n=58 participants at risk
Ranolazine, high dose, oral, BID
Ranolazine: Oral administration, BID; for a maximum of 112 days.
|
Placebo
n=55 participants at risk
Placebo (sugar pill), oral, BID.
Placebo: Oral administration, BID; for a maximum of 112 days.
|
|---|---|---|---|---|
|
Cardiac disorders
Atrial Fibrillation
|
44.6%
29/65 • Number of events 31 • 16 weeks (112 days)
|
40.0%
24/60 • Number of events 33 • 16 weeks (112 days)
|
39.7%
23/58 • Number of events 27 • 16 weeks (112 days)
|
49.1%
27/55 • Number of events 28 • 16 weeks (112 days)
|
|
Cardiac disorders
Atrial Flutter
|
3.1%
2/65 • Number of events 2 • 16 weeks (112 days)
|
0.00%
0/60 • 16 weeks (112 days)
|
5.2%
3/58 • Number of events 3 • 16 weeks (112 days)
|
3.6%
2/55 • Number of events 2 • 16 weeks (112 days)
|
|
Cardiac disorders
Palpitations
|
13.8%
9/65 • Number of events 11 • 16 weeks (112 days)
|
18.3%
11/60 • Number of events 18 • 16 weeks (112 days)
|
19.0%
11/58 • Number of events 19 • 16 weeks (112 days)
|
10.9%
6/55 • Number of events 7 • 16 weeks (112 days)
|
|
Cardiac disorders
Tachycardia
|
1.5%
1/65 • Number of events 1 • 16 weeks (112 days)
|
1.7%
1/60 • Number of events 1 • 16 weeks (112 days)
|
5.2%
3/58 • Number of events 4 • 16 weeks (112 days)
|
1.8%
1/55 • Number of events 1 • 16 weeks (112 days)
|
|
Ear and labyrinth disorders
Vertigo
|
1.5%
1/65 • Number of events 2 • 16 weeks (112 days)
|
1.7%
1/60 • Number of events 2 • 16 weeks (112 days)
|
6.9%
4/58 • Number of events 7 • 16 weeks (112 days)
|
3.6%
2/55 • Number of events 3 • 16 weeks (112 days)
|
|
Gastrointestinal disorders
Constipation
|
1.5%
1/65 • Number of events 1 • 16 weeks (112 days)
|
3.3%
2/60 • Number of events 2 • 16 weeks (112 days)
|
5.2%
3/58 • Number of events 3 • 16 weeks (112 days)
|
1.8%
1/55 • Number of events 1 • 16 weeks (112 days)
|
|
Gastrointestinal disorders
Nausea
|
7.7%
5/65 • Number of events 7 • 16 weeks (112 days)
|
1.7%
1/60 • Number of events 1 • 16 weeks (112 days)
|
6.9%
4/58 • Number of events 7 • 16 weeks (112 days)
|
0.00%
0/55 • 16 weeks (112 days)
|
|
General disorders
Asthenia
|
6.2%
4/65 • Number of events 4 • 16 weeks (112 days)
|
1.7%
1/60 • Number of events 2 • 16 weeks (112 days)
|
8.6%
5/58 • Number of events 5 • 16 weeks (112 days)
|
3.6%
2/55 • Number of events 2 • 16 weeks (112 days)
|
|
General disorders
Chest Pain
|
12.3%
8/65 • Number of events 9 • 16 weeks (112 days)
|
11.7%
7/60 • Number of events 16 • 16 weeks (112 days)
|
6.9%
4/58 • Number of events 4 • 16 weeks (112 days)
|
10.9%
6/55 • Number of events 6 • 16 weeks (112 days)
|
|
General disorders
Fatigue
|
16.9%
11/65 • Number of events 13 • 16 weeks (112 days)
|
16.7%
10/60 • Number of events 14 • 16 weeks (112 days)
|
15.5%
9/58 • Number of events 10 • 16 weeks (112 days)
|
9.1%
5/55 • Number of events 5 • 16 weeks (112 days)
|
|
Investigations
Blood Creatinine increased
|
3.1%
2/65 • Number of events 2 • 16 weeks (112 days)
|
5.0%
3/60 • Number of events 3 • 16 weeks (112 days)
|
0.00%
0/58 • 16 weeks (112 days)
|
1.8%
1/55 • Number of events 1 • 16 weeks (112 days)
|
|
Nervous system disorders
Dizziness
|
9.2%
6/65 • Number of events 7 • 16 weeks (112 days)
|
3.3%
2/60 • Number of events 4 • 16 weeks (112 days)
|
24.1%
14/58 • Number of events 20 • 16 weeks (112 days)
|
12.7%
7/55 • Number of events 8 • 16 weeks (112 days)
|
|
Nervous system disorders
Headache
|
3.1%
2/65 • Number of events 2 • 16 weeks (112 days)
|
3.3%
2/60 • Number of events 2 • 16 weeks (112 days)
|
8.6%
5/58 • Number of events 5 • 16 weeks (112 days)
|
3.6%
2/55 • Number of events 2 • 16 weeks (112 days)
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
7.7%
5/65 • Number of events 6 • 16 weeks (112 days)
|
11.7%
7/60 • Number of events 11 • 16 weeks (112 days)
|
8.6%
5/58 • Number of events 5 • 16 weeks (112 days)
|
10.9%
6/55 • Number of events 6 • 16 weeks (112 days)
|
Additional Information
Angela Capriati MD PhD, Head of Corporate Clinical Research
Menarini Ricerche S.p.A
Phone: 00390555680
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60