A Randomised, Double-blind, Double-dummy, Placebo-controlled, Dose-ranging Phase II Study Assessing Ranolazine in the Maintenance of Sinus Rhythm After Electrical Cardioversion in Patients With Non-permanent Atrial Fibrillation.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 241
- 试验地点
- 4
- 主要终点
- Time From Randomization to First Documented AF Recurrence.
研究概览
简要总结
Dose-ranging Phase II study testing the efficacy and safety of 3 doses of Ranolazine (low, intermediate and high, given BID) versus placebo in maintaining sinus rhythm after successful electrical cardioversion in patients with persistent atrial fibrillation (AFib).
After successful cardioversion and subsequent randomisation, patients report trans-telephonic EGCs on a daily basis to a central core ECG facility.
Maximum treatment duration is 112 days (16 weeks).
详细描述
Patients with persistent AFib are screened for eligibility and undergo direct current cardioversion (DCC). If DCC is successful (defined as persistence of sinus rhythm 2 h post-DCC) patients meeting all the inclusion criteria and none of the exclusion criteria are randomly assigned to the treatment arms (Ranolazine low, intermediate, high dose or placebo, given BID).
Transtelephonic ECG devices (TT-ECG) are used for recording of AFib recurrence to be read by a Central ECG Core Laboratory. Any symptoms indicative of AFib have to be recorded by the patient in a diary.
Study Visits are held for screening (Visit 1), at DCC and randomisation (Visit 2), one week post DCC (Visit 3), after 8 weeks of treatment (Visit 4), and at end of treatment (Visit 5). A safety follow-up telephone call is held 2 weeks after end of treatment.
12-Lead ECGs are performed at every visit.
Safety evaluations include regular safety laboratory blood and urine tests, 12-lead ECGs and the continuous recording of adverse events.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female patients 18 years and older
- •Patients with persistent AF suitable for electrical direct current cardioversion (DCC)
- •A female of childbearing potential may be enrolled providing she has a negative pregnancy test at baseline and is routinely using an effective method of birth control resulting in a low failure rate until end of study
- •Able to give written informed consent before any study related procedure
- •Able to attend all the visits scheduled in the study
排除标准
- •Patients with first diagnosed AF or patients with paroxysmal AF
- •Patients with long-standing persistent AF or permanent AF
- •Patients having known concurrent temporary secondary causes of AF such as alcohol intoxication, pulmonary embolism, hyperthyroidism, pneumonia, hypoxemia, acute pericarditis or myocarditis
- •Patients having undergone atrial catheter ablation for AF
- •Patients carrying a pacemaker
- •Patients with electrolytes imbalances that may cause cardiac arrhythmias, e.g. potassium < 3.5 mmol/L or > 5.5 mmol/L
- •Patients with any contra-indications to Ranexa according to the drug-specific product characteristics
- •Patients taking class I or Class III antiarrhythmic agents within 3 days of planned randomisation
- •Patients taking beta-blockers unless used on stable doses for at least 2 weeks prior to the planned randomisation. Single doses of Intravenous beta-blockers are allowed up to 10 hours from the planned randomisation
- •Patients taking Dronedarone or oral Amiodarone within 2 weeks and 3 months of planned randomisation, respectively
- •Patients with a history of ECG abnormalities that in the opinion of the Investigator render the subject unsuitable for the trial, including history of congenital or a family history of long QT syndrome and a QTc interval ≥500 msec at Screening
- •Patients with congestive heart failure NYHA grade III and IV;
- •Patients with any serious intercurrent illness (including psychiatric and neurological disorders) which, in the opinion of the Investigator, is incompatible with the protocol.
- •Patients taking Metformin at a total daily dose greater than 1000 mg.
- •Patients taking Simvastatin at a total daily dose greater than 20 mg.
研究组 & 干预措施
Ranolazine low dose
Ranolazine, low dose, oral, BID
干预措施: Ranolazine (Drug)
Ranolazine intermediate dose
Ranolazine, intermediate dose, oral, BID
干预措施: Ranolazine (Drug)
Ranolazin high dose
Ranolazine, high dose, oral, BID
干预措施: Ranolazine (Drug)
Placebo
Placebo (sugar pill), oral, BID.
干预措施: Placebo (Drug)
结局指标
主要结局
Time From Randomization to First Documented AF Recurrence.
时间窗: 16 weeks (112 days)
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.
次要结局
- Time From Randomization to First Documented and Confirmed AF Recurrence(16 weeks (112 days))
- Number of Patients With Documented and Confirmed AF Recurrences(16 weeks (112 days))
- Time From Randomization to First Documented AF Recurrence in Patients With Sinus Rhythm 48 Hours After Cardioversion(16 weeks (112 days))
- Number of Patients in Sinus Rhythm 48 Hours After Cardioversion With Documented AF Recurrence(16 weeks (112 days))
- Number of Patients With Documented AF Recurrences(16 weeks (112 days))