A Double-Blind, Placebo-Controlled, Randomized, Multicenter, Proof of Concept and Dose-Finding Phase II Clinical Trial to Investigate the Safety, Tolerability and Efficacy of ADRECIZUMAB in Patients With Septic Shock and Elevated Adrenomedullin
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Adrenomed AG
- 入组人数
- 301
- 试验地点
- 60
- 主要终点
- Endpoints for Primary Objective (Safety and Tolerability of Adrecizumab: Mortality)
研究概览
简要总结
This is a double-blind, placebo-controlled, randomized, multicenter proof of concept and dose-finding phase II study using two doses of ADRECIZUMAB in patients with early septic shock and a bio-ADM plasma concentration at admission of > 70 pg/ml.
详细描述
This is a double-blind, placebo-controlled, randomized, multicenter proof of concept and dose-finding phase II study using two doses of ADRECIZUMAB in patients with early septic shock and a bio-ADM plasma concentration at admission of > 70 pg/ml.
"Early" septic shock is defined as a life-threatening organ dysfunction due to dysregulated host response to a proven or suspected infection which leads to a decline of Mean Arterial Pressure (MAP) < 65 mmHg, which is refractory to fluid resuscitation and requires vasopressors. Early is defined as a maximum of less than 12 hours between onset of the cardiovascular organ-dysfunction and administration of ADRECIZUMAB. Refractoriness to fluid resuscitation is defined as a lack of response to the administration of 30 mL of fluid per kilogram of body weight or is determined according to a clinician's assessment of inadequate hemodynamic results.
It is intended to enroll 300 patients from surgical, medical and mixed ICU at multiple centers in Europe.
All patients will be treated according to "International Guidelines for Management of Severe Sepsis and Septic Shock".
Eligible patients (confirmed by central verification) will be randomized (1:1:2) to ADRECIZUMAB treatment arm A (2 mg/kg) or to ADRECIZUMAB treatment arm B (4 mg/kg) or to placebo as control group. Patients assigned to the treatment arm A or B will be administered a single dose of ADRECIZUMAB as intravenous infusion over approximately 1 hour; patients assigned to the control group will be administered placebo as intravenous infusion over approximately 1 hour.
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
- Double (Participant, Investigator)
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
- •Written informed consent by patient or legal representative (according to country - specific regulations)
- •Male and female patient, age ≥ 18 years
- •Body weight 50 kg - 120 kg
- •Bio-ADM concentration > 70 pg/ml
- •Patient with early septic shock (start of vasopressor therapy < 12 hours)
- •Women of childbearing potential must have a negative serum or urine pregnancy test before randomization
- •Highly effective method of contraception must be maintained for 6 months after study start by women of childbearing potential and sexually active men.
- •No care limitation
排除标准
- •Pre-existing unstable condition (e.g. a recent cerebral hemorrhage or infarct, a recent acute unstable myocardial infarction (all < 3 months), congestive heart failure - New York Heart Association (NYHA) Class IV
- •Patients that required cardiopulmonary resuscitation in the last 4 weeks prior to evaluation for enrollment
- •Severe Chronic Obstructive Pulmonary Disease (COPD) with chronic oxygen need at home (GOLD IV)
- •Any organ or bone marrow transplant within the past 24 weeks
- •Uncontrolled serious hemorrhage (≥ 2 units of blood / platelets in the previous 24 hrs.). Patients may be considered for enrollment if bleeding has stopped and patient is otherwise qualified
- •Uncontrolled hematological / oncological malignancies
- •Absolute neutropenia < 500 per µL
- •Severe chronic liver disease (Child-Pugh C)
- •Systemic fungal infection or active tuberculosis
- •Neuromuscular disorders that impact breathing / spontaneous ventilation
- •Burns > 30% of body surface
- •Plasmapheresis
- •Breastfeeding women
- •Participation in a clinical trial involving another investigational drug within 4 weeks prior to inclusion
- •Unwilling or unable to be fully evaluated for all follow-up visits
研究组 & 干预措施
Control group
Intravenous infusion over approximately 1 hour of single i.v. dose of Placebo of Adrecizumab (control group)
干预措施: Placebo (Biological)
结局指标
主要结局
Endpoints for Primary Objective (Safety and Tolerability of Adrecizumab: Mortality)
时间窗: 90 days
The endpoints for the primary objective is mortality evaluated over the 90 days study period.
Endpoints for Primary Objective (Safety and Tolerability of Adrecizumab: Interruption of Infusion)
时间窗: 90 days
The endpoints for the primary objective are to determine over the 90 days study period: Interruption of infusion due to intolerability of ADRECIZUMAB
Endpoints for Primary Objective (Safety and Tolerability of Adrecizumab: Frequency of TEAEs)
时间窗: 90 days
The endpoints for the primary objective are to determine over the 90 days study period. Number of participants with treatment-emergent adverse events per treatment group.
Endpoints for Primary Objective (Safety and Tolerability of Adrecizumab: Severity and Frequency of TEAEs) - Mild Severity
时间窗: 90 days
The endpoints for the primary objective are to determine over the 90 days study period. Number of participants with treatment-emergent adverse events per treatment group with mild severity treatment emergent events.
Endpoints for Primary Objective (Safety and Tolerability of Adrecizumab: Severity and Frequency of TEAEs) - Severe Severity
时间窗: 90 days
The endpoints for the primary objective are to determine over the 90 days study period. Number of participants with treatment-emergent adverse events per treatment group with severe severity treatment emergent events.
Endpoints for Primary Objective (Safety and Tolerability of Adrecizumab: Severity and Frequency of TEAEs) - Moderate Severity
时间窗: 90 days
The endpoints for the primary objective are to determine over the 90 days study period. Number of participants with treatment-emergent adverse events per treatment group with moderate severity treatment emergent events.
次要结局
- Vasopressor Use (Drug, Duration)(28 days)
- Penalized Sepsis Support Index (pSSI) at 28 Day Follow-up(day 28)
- SSI and pSSI Excluding the Renal Component(day 14 and day 28)
- Changes of Functional Parameter Mean Arterial Pressure During Stay at ICU(28 days)
- Changes of Functional Parameter Creatinine During Stay at ICU(28 days)
- Changes of Functional Parameter Partial Pressure of Oxygen in Arterial Blood(PaO2) / Fraction of Inspired Oxygen (FiO2) During Stay at ICU(28 days)
- Changes of Functional Parameter Inflammatory Marker Interleukin-6 (IL-6) During Stay at ICU(28 days)
- Changes of Functional Parameter Fluid Balance During Stay at ICU(28 days)
- Changes of Functional Parameter Mid-Regional Pro-Adrenomedullin (MR-proADM) During Stay at ICU(28 days)
- Patient Reported Outcomes : Quality of Life by Euro-QoL-5(day 28 and day 90)
- Sepsis Support Index (SSI)(28 days)
- Persistent Organ Dysfunction or Death at 14 and 28 Day Follow-up(day 14 and day 28)
- Vital Signs(7 days)
- Vital Signs - Blood Pressure(7 days)
- Efficacy to be Determined by Sepsis Support Index (SSI)(14 days)
- Penalized Sepsis Support Index (pSSI) at 14 Day Follow-up(day 14)
- Change in Renal Function (Creatinine)(day 1, day 3 and day 7)
- Mortality Rate(day 28)
- SSI Weighted for Mortality(day 14)
- Individual Sepsis Support Index Components(day 14 and day 28)
- Sequential Organ Failure Assessment (SOFA) Score : Composite Measure: SOFA Score and Its Changes Over Time(28 days)
- Duration of Stay at ICU/ Hospital(90 days)
- Changes of Functional Parameter Blood Lactate During Stay at ICU(28 days)
- Changes of Functional Parameter Inflammatory Marker Procalcitonine (PCT) During Stay at ICU(28 days)
- Changes of Functional Parameter Dipeptidyl Peptidase 3 (DPP3) During Stay at ICU(28 days)
- Vasopressor Use (Drug, Highest Dose)(28 days)
- Change in Renal Function (penKid)(day 1, day 3 and day 7)