A Phase IV Study to Assess the Effect of Naltrexone Hydrochloride Extended Release (ER) and Bupropion Hydrochloride ER Combination (Contrave®/Mysimba®) on the Occurrence of Major Adverse Cardiovascular Events
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 8,600
- 试验地点
- 119
- 主要终点
- Occurrence of Cardiovascular Death
研究概览
简要总结
A randomized, double-blinded, placebo controlled study intended to capture cardiovascular outcomes during real-world use of naltrexone/bupropion (NB).
详细描述
This multi-center, prospective, randomized, pragmatic, double-blinded study has been designed to capture cardiovascular (CV) outcomes during the real-world use of NB after initial randomization. The aim of the study is to assess whether patients receiving treatment with NB are at an elevated risk of experiencing MACE compared with patients receiving placebo. Both patient groups will also be counselled to lose weight via a reduced-calorie diet and increased physical activity.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Sponsor will be blinded
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
- •Patient age ≥18 years at screening
- •Able to understand the key components of the study, as described in the written informed consent document, and willing and able to provide written informed consent
- •BMI ≥30 kg/m2 (obese) or ≥27 kg/m2 (overweight) in the presence of at least 1 weight-related comorbidity (eg, hypertension, type 2 diabetes mellitus, or dyslipidemia)
- •At increased risk of adverse cardiovascular outcomes:
- •In the opinion of the investigator, has a high likelihood of cardiovascular disease with at least 1 of the following:
- •History of documented MI >90 days prior to screening
- •History of coronary revascularization (ie, coronary artery bypass graft surgery, stent placement, percutaneous transluminal coronary angioplasty, or laser atherectomy) >90 days prior to screening
- •History of carotid or peripheral revascularization (ie, carotid endarterectomy, lower extremity atherosclerotic disease atherectomy, repair of abdominal aorta aneurysm, femoral or popliteal bypass) >90 days prior to screening
- •Angina with ischemic changes (resting echocardiogram (ECHO), ECG changes on a graded exercise test (GXT), or positive cardiac imaging study)
- •Ankle brachial index <0.9 (by simple palpation) within prior 2 years or
- •Type 2 diabetes mellitus with at least 2 of the following:
- •Hypertension (controlled with or without pharmacotherapy at <145/95 mmHg)
- •Dyslipidemia requiring pharmacotherapy
- •Documented low HDL cholesterol (<50 mg/dL in women or <40 mg/dL in men) within the prior 12 months
- •Current tobacco smoker
- •Patients who have completed a washout (2-weeks or 5 half-lives, whichever is longer) of the prohibited concomitant medication(s) at screening
- •Subject willing to comply with daily completion of an eDiary using a mobile smartphone application
排除标准
- •Using prescription medications, other than Contrave/Mysimba, or surgical or medical device interventions for weight loss
- •History of MI or stroke within 90 days prior to screening
- •Uncontrolled hypertension, defined as systolic BP ≥160 mmHg and/or >100 mmHg diastolic BP on the average of 3 seated BP measurements after the patient has been at rest for at least 5 minutes
- •Meets any of the following criteria:
- •Confirmed end-stage renal disease (ie, a degree of kidney failure severe enough to require dialysis or kidney transplantation for survival characterized by a severe reduction in glomerular filtration rate [<15 mL/minute/1.73 m2] and other manifestations including increased serum creatinine),
- •Severe hepatic impairment (Child-Pugh score 10 to 15 [Class C]),
- •Hemodynamic instability, including patients with severe heart failure (New York Heart Association Class IV)
- •Seizure disorders or history of seizures, not including subjects with a history of pediatric febrile seizures
- •Use of other bupropion-containing products (including but not limited to Wellbutrin, Wellbutrin SR, Wellbutrin XL, and Aplenzin)
- •Active anorexia nervosa or bulimia
- •Chronic opioid or opiate agonist (eg, methadone) or partial agonists (eg, buprenorphine) use, or acute opioid withdrawal or has a positive urine drug result for opioids at screening
- •Undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs
- •Concomitant administration of MAOIs. This also includes use of reversible MAOIs, such as linezolid or intravenous methylene blue. At least 14 days should elapse between discontinuation of MAOIs and initiation of treatment with Contrave/Mysimba.
- •Subject has any disease or condition, or use of any pharmacological agent to treat the disease/condition, that, in the opinion of the investigator, would contraindicate study participation
- •Known allergy to bupropion, naltrexone, or any other component of Contrave/Mysimba
- •Pregnant or nursing
- •Known life-threatening arrythmias, including Brugada syndrome
- •Participation in any other concurrent investigational trial
研究组 & 干预措施
Naltrexone/Bupropion (NB)
Patients will be randomly assigned to NB (naltrexone 8 mg and bupropion 90 mg) extended-release oral tablet.
干预措施: Naltrexone-Bupropion (NB) Combination (Drug)
Placebo
Patients will be randomly assigned to placebo.
干预措施: Placebo (Drug)
结局指标
主要结局
Occurrence of Cardiovascular Death
时间窗: Treatment initiation through 1 year following treatment termination.
Occurrence of cardiovascular death in number of study patients receiving NB compared with number of study patients receiving placebo.
Occurrence of Non-fatal Myocardial Infarction (MI)
时间窗: Treatment initiation through 1 year following treatment termination.
Occurrence of MI in number of study patients receiving NB compared with number of study patients receiving placebo. MI will be identified using current standard diagnostic criteria, such as the 2017 Cardiovascular and Stroke Endpoints Definitions for Clinical Trials.
Occurrence of Non-fatal Stroke
时间窗: Treatment initiation through 1 year following treatment termination.
Occurrence of non-fatal stroke in number of study patients receiving NB compared with number of study patients receiving placebo. Stroke will be identified using current standard diagnostic criteria, such as the 2017 Cardiovascular and Stroke Endpoints Definitions for Clinical Trials.
次要结局
- Comparative Rates of Non-fatal Myocardial Infarction (MI)(Treatment initiation through 1 year following treatment termination.)
- Comparative Rates of Non-fatal Stroke(Treatment initiation through 1 year following treatment termination.)
- Comparative Rates of Cardiovascular Death(Treatment initiation through 1 year following treatment termination.)