A Randomized, Double-blind, Placebo-controlled, Multi-centre, Sequential Design, Phase IIa Study to Evaluate Safety and Tolerability of Epicardial Injections of AZD8601 During Coronary Artery Bypass Grafting Surgery

AstraZeneca1 个研究点分布在 1 个国家目标入组 11 人开始时间: 2018年2月5日最近更新: 2024年10月10日

适应症

干预措施

试验速览

阶段: 2 期
状态: 已完成
发起方: AstraZeneca
入组人数: 11
试验地点: 1
主要终点: Number of Subjects With High Values of Erythrocytes, Particle Concentration

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

This is a randomized, double-blind, placebo-controlled, sequential design, multicentre study in patients with moderately impaired systolic function undergoing CABG surgery. Twenty four (24) patients scheduled for elective bypass surgery will be randomized (up to approximately 33 patients if replacements are needed). The objective is to investigate safety and tolerability of AZD8601 following epicardial injection in patients undergoing Coronary Artery Bypass Grafting (CABG) surgery with moderately impaired systolic function. At Visit 3 patients will receive either AZD8601 or placebo as epicardial injections and will then be followed up at 14 days (telephone visit) and 1, 3 and 6 months (on-site) post-surgery.

研究设计

研究类型: Interventional
分配方式: Randomized
干预模型: Sequential
主要目的: Treatment
盲法: Triple (Participant, Care Provider, Investigator)

入排标准

年龄范围: 18 Years 至 99 Years（Adult, Older Adult）
性别: All
接受健康志愿者: 否

入选标准

•For inclusion in the study patients should fulfil the following criteria at Visit 1 and/or 2:
•Provision of signed and dated informed consent prior to any study specific procedures
•Males and females:
•Males must be surgically sterile or using an acceptable method of contraception
•Females must be of non-childbearing potential confirmed at screening by fulfilling one of the following criteria a) postmenopausal defined as amenorrhoea for at least 12 months or more following cessation of all exogenous hormonal treatments and follicle-stimulating hormone (FSH) levels in the postmenopausal range, b) documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation
•Age >18 years
•Indication for elective CABG surgery enrolled at least 15 days before the planned surgery
•Moderately reduced global LVEF at rest (30% ≤ LVEF ≤ 50%) from medical records
•If patient is on statin, ACE inhibitor/ARB, and/or beta-blocker, the dose should be stable at least 2 weeks prior to Visit 1
•Patients who are blood donors should not donate blood during the study and for 3 months following their last dose of AZD8601.

排除标准

•Patients should not enter the study if any of the following exclusion criteria are fulfilled:
•Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
•Previous randomisation in the present study
•Participation in another clinical study with an investigational product during the last 3 months
•BMI > 35 kg/m2 OR poor image window for echocardiography
•Need for CABG emergency operation. (Emergency operation is defined as significant symptom status worsening in CAD, such as crescendo angina, unstable angina or ACS requiring rescheduling the revascularization. CAD should be stable at least 3 months prior to Visit 3.)
•History of ventricular arrhythmia (≥ Lown III) without Implantable Cardiac Defibrillator (ICD) History of any clinically significant disease or disorder which, in the opinion of the PI, may either put the patient at risk because of participation in the study, or influence the results or the patient's ability to participate in the study
•Severe co-morbidities that can interfere with the execution of the study, interpretation of study results or affect the safety of the patient, in judgement of the investigator
•eGFR ≤ 30 mL/min (derived from creatinine clearance, calculated by local lab)
•For CFVR (Visit 1) and sMBF (Visit 2) measurement:
•Known severe adverse reactions to adenosine
•Known elevated intracranial pressure
•AV block ≥ second degree and/or sick sinus syndrome in patient without pacemaker
•Heart rate < 40 bpm (ECG verified)
•Systolic blood pressure < 90 mmHg
•Asthma or COPD with strong reactive component in judgement of investigator
•Treatment with dipyridamole (e.g. Persantin or Asasantin), theophyllamine or fluvoxamine that cannot be paused
•Inability to comply with the protocol
•History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity to drugs with a similar chemical structure or class as study drugs
•Patients unable to give their consent or communicate reliably with the investigator or vulnerable patients e.g., kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order
•Positive hepatitis C antibody hepatitis B virus surface antigen or hepatitis B virus core antibody or human immunodeficiency virus, at Visit 1
•Known history of drug or alcohol abuse
•Any concomitant medications that are known to be associated with Torsades de Pointes
•History of QT prolongation associated with other medications that required discontinuation of that medication
•Congenital long QT syndrome
•History of arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia), which is symptomatic or requires treatment (CTCAE Grade 3).
•Current atrial fibrillation as well as paroxysmal atrial fibrillation.

研究组 & 干预措施

Low dose AZD8601 (3 mg)

Experimental

8 patients will be randomised to receive 3 mg AZD8601

干预措施: AZD8601 (Drug)

High dose AZD8601 (30 mg)

Experimental

8 patients will be randomised to receive 30 mg AZD8601

干预措施: AZD8601 (Drug)

Placebo

Placebo Comparator

8 patients will be randomised to receive placebo injections

干预措施: Placebo (Drug)