A Prospective, Multi-centric, Randomized, Double-blind, Parallel, Saline Controlled Phase II Safety and Efficacy Study of PMZ-2010 as a Resuscitative Agent for Hypovolemic Shock to be Used Along With Standard Shock Treatment.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 50
- 试验地点
- 7
- 主要终点
- Incidence of PMZ-2010 related adverse events
研究概览
简要总结
This is a prospective, multi-centric, randomized, double-blind, parallel, controlled phase-II efficacy clinical study of PMZ-2010 therapy in patients with hypovolemic shock.
Centhaquine is highly safe and well tolerated. Toxicological studies showed high safety margin in preclinical studies. Its safety and tolerability has been demonstrated in a human phase I study in 25 subjects (CTRI/2014/06/004647; NCT02408731).
详细描述
Centhaquine (previously used names, centhaquin and PMZ-2010; International Non-proprietary Name (INN) recently approved by WHO is centhaquine) has been found to be an effective resuscitative agent in rat, rabbit and swine models of hemorrhagic shock, it decreased blood lactate, increased mean arterial pressure, cardiac output, and decreased mortality. An increase in cardiac output during resuscitation is mainly attributed to an increase in stroke volume. Centhaquine acts on the venous α2B-adrenergic receptors and enhances venous return to the heart, in addition, it produces arterial dilatation by acting on central α2A-adrenergic receptors to reduce sympathetic activity and systemic vascular resistance.
Unlike presently used vasopressors, centhaquine increased mean arterial pressure by increasing stroke volume and cardiac output, and it decreased systemic vascular resistance. The most common adverse effects of vasopressors as a class include arrhythmias, fluid extravasation, and ischemia. Centhaquine does NOT act on beta-adrenergic receptors, and therefore the risk of arrhythmias is mitigated. It is NOT a vasopressor; however, it increases blood pressure and cardiac output by augmenting venous blood return to the heart and enhanced tissue perfusion by arterial dilatation. Enhancing tissue perfusion is a significant advantage over existing vasopressors.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult males or females aged 18-70 years.
- •Patients with Hypovolemic shock due to blood loss admitted to the emergency room or ICU with systolic blood pressure ≤ 90 mmHg at presentation and continue to receive standard shock treatment (endotracheal intubation; fluid resuscitation and vasopressors). Standard of care to be provided to the patients shall be the one used in the particular hospital setup.
- •Body weight 45 kg - 85 kg.
- •Female subject is either: (1) Not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy) or, (2) If of childbearing potential, agrees to use any of the following effective separate forms of contraception throughout the study, up to and including the follow-up visits: Condoms, sponge, foams, jellies, diaphragm or intrauterine device, or A vasectomised partner OR abstinence.
排除标准
- •Terminal illness
- •Development of any other terminal illness not associated with Hypovolemic shock due to blood loss during the 28 day observation period
- •Patient with severe brain injury or with a Glasgow Coma Scale (GCS) < 8
- •Type of injury is not known
- •Inability to obtain intravenous access
- •Known pregnancy
- •Cardiopulmonary resuscitation (CPR) before randomization
- •Presence of a do not resuscitate order
- •Patient taking beta adrenergic antagonists
- •Untreated tension pneumothorax
- •Untreated cardiac tamponade
- •Bilateral absent pupillary light reflex (both pupils fixed and dilated)
- •Patient is participating in another interventional study
- •Patients with systemic diseases which were already present before having trauma, such as: cancer, chronic renal failure, liver failure, decompensated heart failure or AIDS
研究组 & 干预措施
Normal Saline
Hypovolemic shock patients will be provided the standard of care. Following randomization 100 ml (equal volume to experimental arm) of normal saline will be administered intravenously over 1 hour.
干预措施: Normal Saline (Drug)
PMZ-2010 (centhaquine)
Hypovolemic shock patients will be provided the standard of care. Following randomization PMZ-2010 (0.01 mg/kg) will be administered intravenously over 1 hour in 100 mL of normal saline.
干预措施: Centhaquine (Drug)
结局指标
主要结局
Incidence of PMZ-2010 related adverse events
时间窗: 28 days
The primary objective of the study is to determine incidence of drug (PMZ-2010) related adverse events.
次要结局
- Vasopressor(s) infused(48 hours)
- Change in fibrinogen(48 hours)
- Doses of study drug(48 hours)
- Change in platelet count(48 hours)
- Change in international normalized ratio (INR)(48 hours)
- Change in Acute Respiratory Distress Syndrome(28 days)
- Incidence of mortality(28 days)
- Change in blood lactate level(48 hours)
- Change in Multiple Organ Dysfunction Syndrome Score(28 days)
- Change in prothrombin time(48 hours)
- Change in Glasgow coma score(28 days)
- Volume of blood products administered(48 hours)
- Volume of fluid administered(48 hours)
- Change in systolic and diastolic blood pressure(48 hours)
- Change in base-deficit(48 hours)
- Stay in hospital, in ICU and/or on Ventilator(28 days)