Clinical trial NCT06351150: Efficacy and Safety of Angiotensin II Injection Versus Placebo in Patients With Refractory Distributed Shock
Official title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase III Trial to Evaluate the Efficacy and Safety of Angiotensin II Injection in the Background Treatment of Catecholamines and Other Vasopressors in Chinese Adult Patients With Refractory Distributive Shock
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Vasodilatory Shock
Lead sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2024-04-08
Enrollment: 214
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A randomized, double-blind, placebo-controlled study on the treatment of refractory distributed shock with angiotensin II injection, with a random ratio of 1:1. Assuming a success rate of 25% for the main therapeutic endpoint in the control group and 50% for the experimental group, a total of 214 subjects will be enrolled, including 107 in the experimental group and 107 in the control group.


Eligibility criteria: Inclusion Criteria:

* age: 18 years to 75 years old, male or female;
* diagnosis of distributive shock;
* on the basis of the treatment of total vasoactive drugs dose \> 0.2 μg/kg/min norepinephrine (or equivalent dose of another vasoactive drug: such as epinephrine \> 0.2 μg/kg/min, dopamine \> 30 μg/kg/min, phenylephrine \> 2 μg/kg/min, vasopressin \> 0.08 U/min) and continuous treatment for at least 6 hours and no more than 48 hours, the patient's mean arterial pressure can still only be maintained between 55 and 70 mmHg, or do not reach the target MAP assessed by clinicians, it can be diagnosed as refractory distributive shock.
* have central venous access and arterial catheters, and are expected to be present for at least the first 48 hours of the study.
* indwelling catheter, and expected to be present for at least the first 48 hours of the study.
* patient has received at least 30 mL/kg of crystalloid or colloid volume in the previous 24 hours or has undergone adequate volume resuscitation in the opinion of the investigator.
* patients must have one of the following criteria with clinical features of high-output shock

  1. Central venous oxygen saturation (ScVO2) \> 70% (via saturation catheter or central venous blood gas) and central venous pressure (CVP) \> 8 mmHg.
  2. cardiac index (CI) \> 2.3 L/min/m2.
* the patient or legal representative is willing and able to provide written informed consent and comply with all protocol requirements.

Exclusion Criteria:

* Patients with burns \> 20% of total body surface area;
* Patients with cardiovascular (CV) SOFA score ≤ 3;
* Patients with acute coronary syndrome requiring interventional therapy;
* Patients treated with Extracorporeal Membrane Oxygenation (ECMO);
* Patients with end-stage liver failure (Model for end-stage liver disease score (MELD) \> 30).
* Patients with a diagnosis of asthma or bronchospasm.
* Patients with a diagnosis of acute mesenteric ischemia, or patients with suspected acute mesenteric ischemia.
* Patients with a history, presence, or high suspicion of aortic dissection or abdominal aortic aneurysm, or patients diagnosed with aortic dissection or abdominal aortic aneurysm.
* Patients who have been diagnosed with malignant tumor within the past 2 years, except for early malignant tumors (carcinoma in situ or stage I tumor) that have been radically treated or expected to recover after treatment, such as adequately treated thyroid cancer, cervical carcinoma in situ, basal cell or squamous cell carcinoma.
* Patients with Raynaud's phenomenon, systemic sclerosis or vasospastic disease.
* Patients with life expectancy ≤ 24 hours as assessed by the study physician.
* Patients with active bleeding who are expected to require transfusion of \> 4 units of packed red blood cells within 48 hours of study start.
* Patients with active bleeding and hemoglobin \< 7 g/dL or any other condition that contraindicates serial blood sampling.
* Patients with absolute neutrophil count (ANC) \< 1000 cells/mm3.
* Patients with known hypersensitivity to angiotensin II injection and its excipients.
* Patients who are currently participating in another interventional clinical trial.
* Blood/urine pregnancy test should be performed for patients with known pregnancy at screening and those with clinical suspicion of pregnancy.
* Patients who are considered unstable by the investigator or have any condition that would affect the safety of the study or the interpretation of the study results, or that would prevent the patient from completing the study, including but not limited to cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, hematological, psychiatric, or major physical disorders. For example: patients with arrhythmia, uncontrolled hyperglycemia, cerebrovascular disease, uncontrolled hypertension, autoimmune disease requiring daily use of ≥ 500 mg hydrocortisone or equivalent glucocorticoids, etc.

Primary outcomes:
measure: Proportion of subjects with blood pressure response at 3 hours after administration of study drug
timeFrame: 3 hours after dose
Secondary outcomes:
measure: Sequential Organ Failure Assessment (SOFA) total score
timeFrame: 48 hours after dose
measure: Cardiovascular SOFA subscore
timeFrame: 48 hours after dose
measure: Mortality at Day 7
timeFrame: Day 7 after dose
measure: Mortality at Day 28
timeFrame: Day 28 after dose
measure: Proportion of subjects with blood pressure response at 1 hour after administration
timeFrame: 1 hour after dose
measure: Proportion of subjects with blood pressure response at 2 hours after administration
timeFrame: 2 hours after dose
measure: Change in background vasoactive agent dose from 0 to 48 hours
timeFrame: 48 hours after dose
measure: Absolute change in blood lactate from 0 to 3 hours
timeFrame: 3 hours after dose
measure: Absolute change in blood lactate from 3 to 48 hours
timeFrame: 3 to 48 hours after dose
measure: Absolute change in heart rate from 0 to 3 hours
timeFrame: 3 hours after dose
measure: Absolute change in heart rate from 3 to 48 hours
timeFrame: 3 to 48 hours after dose
measure: Adverse events (AE)
timeFrame: From drug administration to the end of the study, a total of 28 days
measure: Serious adverse events (SAE)
timeFrame: From drug administration to the end of the study, a total of 28 days
Other outcomes:
Locations:
city: Hefei
country: China
facility: The Second People's Hospital of Hefei
state: Anhui
city: Wuhu
country: China
facility: The Frist Affiliated Hospital of Wannan Medical College
state: Anhui
city: Beijing
country: China
facility: Beijing Tiantan Hospital,Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
city: Chongqing
country: China
facility: The Frist Affiliated Hospital of Chongqing Medical University
state: Chongqing
city: Fuzhou
country: China
facility: The people's Hospital of the University of traditional Chinese medicine in Fujian
state: Fujian
city: Lanzhou
country: China
facility: Gansu Provincial Hospital
state: Gansu
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Sun Yat sen University
state: Guangdong
city: Guangzhou
country: China
facility: Zhujiang Hospital of Southern Medical University
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Jinan University
state: Guangdong
city: Qingyuan
country: China
facility: Qingyuan Hospital Affiliated to Guangzhou Medical University
state: Guangdong
city: Shantou
country: China
facility: The First Affiliated Hospital of Shantou University Medical College
state: Guangdong
city: Shenzhen
country: China
facility: Peking University Shenzhen Hospital
state: Guangdong
city: Guilin
country: China
facility: The People's Hospital of Guangxi Zhuang Autonomous Region
state: Guangxi
city: Liuzhou
country: China
facility: Liuzhou General Hospital
state: Guangxi
city: Guiyang
country: China
facility: The Affiliated Hospital of Guizhou Medical University
state: Guizhou
city: Baoding
country: China
facility: The Affiliated Hospital of Hebei University
state: Hebei
city: Harbin
country: China
facility: The First Affiliated Hospital of Harbin Medical University
state: Heilongjiang
city: Bengbu
country: China
facility: The First Affiliated Hospital of Bengbu Medical College
state: Henan
city: Luoyang
country: China
facility: The First Affiliated Hospital of Henan University of Science and Technology
state: Henan
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Wuhan
country: China
facility: Union Hospital, Tongji Medical College of huazhong university of science and technology
state: Hubei
city: Wuhan
country: China
facility: Wuhan Third Hospital
state: Hubei
city: Changsha
country: China
facility: Xiangya Hospital Central South University
state: Hunan
city: Changsha
country: China
facility: Hunan Provincial People's Hospital
state: Hunan
city: Nanjing
country: China
facility: Jiangsu Province Hospital
state: Jiangsu
city: Wuxi
country: China
facility: Wuxi People's Hospital
state: Jiangsu
city: Nanchang
country: China
facility: The Frist Affiliated Hospital of Nanchang University
state: Jiangxi
city: Shenyang
country: China
facility: Shengjing Hospital of China Medical University
state: Liaoning
city: Xi'an
country: China
facility: The Second Affiliated Hospital of Xi'an Jiaotong University
state: Shaanxi
city: Jinan
country: China
facility: Qilu Hospital of Shandong University
state: Shandong
city: Zibo
country: China
facility: Zibo Central Hospital
state: Shandong
city: Shanghai
country: China
facility: Shanghai General Hospital
state: Shanghai
city: Taiyuan
country: China
facility: The First Hospital of Shanxi Medical University
state: Shanxi
city: Xi'an
country: China
facility: The Frist Affiliated Hospital of Xi'an Jiaotong University
state: Shanxi
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
state: Sichuan
city: Chengdu
country: China
facility: Sichuan Provincial People's Hospital
state: Sichuan
city: Tianjin
country: China
facility: Tianjin Medical University General Hospital
state: Tianjin
city: Tianjin
country: China
facility: Tianjin First Central Hospital
state: Tianjin
city: Ürümqi
country: China
facility: The First Affiliated Hospital of Xinjiang Medical University
state: Xinjiang
city: Ningbo
country: China
facility: The Frist Affiliated Hospital of Ningbo University
state: Zhejiang
city: Taizhou
country: China
facility: Taizhou hospital of Zhejiang Province
state: Zhejiang
Study officials:
References: