Efficacy and Safety of Angiotensin II Injection Versus Placebo in Patients With Refractory Distributed Shock
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
1 other identifier
interventional
214
1 country
42
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_3
Started Jul 2024
Typical duration for phase_3
42 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 2, 2024
CompletedFirst Posted
Study publicly available on registry
April 8, 2024
CompletedStudy Start
First participant enrolled
July 23, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 1, 2027
January 23, 2025
April 1, 2024
2.9 years
April 2, 2024
January 21, 2025
Conditions
Outcome Measures
Primary Outcomes (1)
Proportion of subjects with blood pressure response at 3 hours after administration of study drug
Defined as MAP ≥ 75 mmHg or MAP increase ≥ 10 mmHg from baseline compared to baseline without an increase in the dose of background vasoactive agents
3 hours after dose
Secondary Outcomes (13)
Sequential Organ Failure Assessment (SOFA) total score
48 hours after dose
Cardiovascular SOFA subscore
48 hours after dose
Mortality at Day 7
Day 7 after dose
Mortality at Day 28
Day 28 after dose
Proportion of subjects with blood pressure response at 1 hour after administration
1 hour after dose
- +8 more secondary outcomes
Study Arms (2)
Angiotensin Ⅱ Injection
EXPERIMENTALAngiotensin II injection is administered via central vein, and the drug dosage is adjusted according to Mean Arterial Pressure (MAP), with an allowable dose of 1.25\~160 ng/kg/min. Maximum 168 h.
Placebo
PLACEBO COMPARATORThe placebo is administered via central vein, and the drug dosage is adjusted according to MAP, with an allowable dose of 1.25\~160 ng/kg/min. Maximum 168 h.
Interventions
1、Angiotensin II injection is a naturally occurring octapeptide hormone in the human renin angiotensin aldosterone system (RAAS). It is the main effector molecule of the RAAS system and one of the strongest known vasoconstrictors, involved in neurohumoral regulation.
0.9% sodium chloride injection, not containing active ingredients.
Eligibility Criteria
You may qualify if:
- 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
- Central venous oxygen saturation (ScVO2) \> 70% (via saturation catheter or central venous blood gas) and central venous pressure (CVP) \> 8 mmHg.
- 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.
You may not qualify if:
- 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.
- +3 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (42)
The Second People's Hospital of Hefei
Hefei, Anhui, 230011, China
The Frist Affiliated Hospital of Wannan Medical College
Wuhu, Anhui, 241001, China
Beijing Tiantan Hospital,Capital Medical University
Beijing, Beijing Municipality, 100070, China
Peking Union Medical College Hospital
Beijing, Beijing Municipality, 100730, China
The Frist Affiliated Hospital of Chongqing Medical University
Chongqing, Chongqing Municipality, 400010, China
The people's Hospital of the University of traditional Chinese medicine in Fujian
Fuzhou, Fujian, 350108, China
Gansu Provincial Hospital
Lanzhou, Gansu, 730000, China
The First Affiliated Hospital of Sun Yat sen University
Guangzhou, Guangdong, 510062, China
Zhujiang Hospital of Southern Medical University
Guangzhou, Guangdong, 510260, China
The First Affiliated Hospital of Jinan University
Guangzhou, Guangdong, 510632, China
Qingyuan Hospital Affiliated to Guangzhou Medical University
Qingyuan, Guangdong, 511518, China
The First Affiliated Hospital of Shantou University Medical College
Shantou, Guangdong, 515041, China
Peking University Shenzhen Hospital
Shenzhen, Guangdong, 518036, China
The People's Hospital of Guangxi Zhuang Autonomous Region
Guilin, Guangxi, 543300, China
Liuzhou General Hospital
Liuchow, Guangxi, 545026, China
The Affiliated Hospital of Guizhou Medical University
Guiyang, Guizhou, 550004, China
The Affiliated Hospital of Hebei University
Baoding, Hebei, 050031, China
The First Affiliated Hospital of Harbin Medical University
Harbin, Heilongjiang, 150007, China
The First Affiliated Hospital of Bengbu Medical College
Bengbu, Henan, 233099, China
The First Affiliated Hospital of Henan University of Science and Technology
Luoyang, Henan, 450052, China
The First Affiliated Hospital of Zhengzhou University
Zhengzhou, Henan, 450052, China
Union Hospital, Tongji Medical College of huazhong university of science and technology
Wuhan, Hubei, 430022, China
Wuhan Third Hospital
Wuhan, Hubei, 430060, China
Xiangya Hospital Central South University
Changsha, Hunan, 140008, China
Hunan Provincial People's Hospital
Changsha, Hunan, 410001, China
Jiangsu Province Hospital
Nanjing, Jiangsu, 210029, China
Wuxi People's Hospital
Wuxi, Jiangsu, 214023, China
The Frist Affiliated Hospital of Nanchang University
Nanchang, Jiangxi, 330006, China
Shengjing Hospital of China Medical University
Shenyang, Liaoning, 110004, China
The Second Affiliated Hospital of Xi'an Jiaotong University
Xi'an, Shaanxi, 710004, China
Qilu Hospital of Shandong University
Jinan, Shandong, 250000, China
Zibo Central Hospital
Zibo, Shandong, 255020, China
Shanghai General Hospital
Shanghai, Shanghai Municipality, 200080, China
The First Hospital of Shanxi Medical University
Taiyuan, Shanxi, 030001, China
The Frist Affiliated Hospital of Xi'an Jiaotong University
Xi’an, Shanxi, 710048, China
West China Hospital of Sichuan University
Chengdu, Sichuan, 610044, China
Sichuan Provincial People's Hospital
Chengdu, Sichuan, 610072, China
Tianjin Medical University General Hospital
Tianjin, Tianjin Municipality, 300052, China
Tianjin First Central Hospital
Tianjin, Tianjin Municipality, 300190, China
The First Affiliated Hospital of Xinjiang Medical University
Ürümqi, Xinjiang, 830054, China
The Frist Affiliated Hospital of Ningbo University
Ningbo, Zhejiang, 315020, China
Taizhou hospital of Zhejiang Province
Taizhou, Zhejiang, 317000, China
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 2, 2024
First Posted
April 8, 2024
Study Start
July 23, 2024
Primary Completion (Estimated)
June 1, 2027
Study Completion (Estimated)
December 1, 2027
Last Updated
January 23, 2025
Record last verified: 2024-04