Efficacy and Safety of Angiotensin II Injection Versus Placebo in Patients With Refractory Distributed Shock

January 21, 2025 updated by: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

214

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Anhui
      • Hefei, Anhui, China, 230011
        • Not yet recruiting
        • The Second People's Hospital of Hefei
        • Contact:
      • Wuhu, Anhui, China, 241001
        • Not yet recruiting
        • The Frist Affiliated Hospital of Wannan Medical College
        • Contact:
    • Beijing
      • Beijing, Beijing, China, 100730
        • Not yet recruiting
        • Peking Union Medical College Hospital
        • Contact:
      • Beijing, Beijing, China, 100070
        • Not yet recruiting
        • Beijing Tiantan Hospital,Capital Medical University
        • Contact:
    • Chongqing
      • Chongqing, Chongqing, China, 400010
        • Not yet recruiting
        • The Frist Affiliated Hospital of Chongqing Medical University
        • Contact:
    • Fujian
      • Fuzhou, Fujian, China, 350108
        • Not yet recruiting
        • The people's Hospital of the University of traditional Chinese medicine in Fujian
        • Contact:
    • Gansu
      • Lanzhou, Gansu, China, 730000
        • Not yet recruiting
        • Gansu Provincial Hospital
        • Contact:
    • Guangdong
      • Guangzhou, Guangdong, China, 510632
        • Not yet recruiting
        • The First Affiliated Hospital of Jinan University
        • Contact:
      • Guangzhou, Guangdong, China, 510260
        • Not yet recruiting
        • Zhujiang Hospital of Southern Medical University
        • Contact:
      • Guangzhou, Guangdong, China, 510062
        • Not yet recruiting
        • The First Affiliated Hospital of Sun Yat sen University
        • Contact:
      • Qingyuan, Guangdong, China, 511518
        • Not yet recruiting
        • Qingyuan Hospital Affiliated to Guangzhou Medical University
        • Contact:
      • Shantou, Guangdong, China, 515041
        • Not yet recruiting
        • The First Affiliated Hospital of Shantou University Medical College
        • Contact:
      • Shenzhen, Guangdong, China, 518036
        • Not yet recruiting
        • Peking University Shenzhen Hospital
        • Contact:
    • Guangxi
      • Guilin, Guangxi, China, 543300
        • Not yet recruiting
        • The People's Hospital of Guangxi Zhuang Autonomous Region
        • Contact:
      • Liuzhou, Guangxi, China, 545026
        • Not yet recruiting
        • Liuzhou General Hospital
        • Contact:
    • Guizhou
      • Guiyang, Guizhou, China, 550004
        • Not yet recruiting
        • The Affiliated Hospital of Guizhou Medical University
        • Contact:
    • Hebei
      • Baoding, Hebei, China, 050031
        • Not yet recruiting
        • The Affiliated Hospital of Hebei University
        • Contact:
    • Heilongjiang
      • Harbin, Heilongjiang, China, 150007
        • Not yet recruiting
        • The First Affiliated Hospital of Harbin Medical University
        • Contact:
    • Henan
      • Bengbu, Henan, China, 233099
        • Not yet recruiting
        • The First Affiliated Hospital of Bengbu Medical College
        • Contact:
      • Luoyang, Henan, China, 450052
        • Not yet recruiting
        • The first affiliated hospital of Henan University of science and technology
        • Contact:
      • Zhengzhou, Henan, China, 450052
        • Not yet recruiting
        • The first affiliated hospital of Zhengzhou university
        • Contact:
    • Hubei
      • Wuhan, Hubei, China, 430060
        • Not yet recruiting
        • Wuhan Third Hospital
        • Contact:
      • Wuhan, Hubei, China, 430022
        • Not yet recruiting
        • Union Hospital, Tongji Medical College of Huazhong University of Science and Technology
        • Contact:
    • Hunan
      • Changsha, Hunan, China, 140008
        • Not yet recruiting
        • Xiangya Hospital Central South University
        • Contact:
      • Changsha, Hunan, China, 410001
        • Not yet recruiting
        • Hunan Provincial People's Hospital
        • Contact:
    • Jiangsu
      • Nanjing, Jiangsu, China, 210029
        • Not yet recruiting
        • Jiangsu Province Hospital
        • Contact:
      • Wuxi, Jiangsu, China, 214023
        • Not yet recruiting
        • Wuxi People's Hospital
        • Contact:
    • Jiangxi
      • Nanchang, Jiangxi, China, 330006
        • Not yet recruiting
        • The Frist Affiliated Hospital of Nanchang University
        • Contact:
    • Liaoning
      • Shenyang, Liaoning, China, 110004
        • Not yet recruiting
        • Shengjing Hospital Of China Medical University
        • Contact:
    • Shaanxi
      • Xi'an, Shaanxi, China, 710004
        • Not yet recruiting
        • The Second Affiliated Hospital of Xi'an Jiaotong University
        • Contact:
    • Shandong
      • Jinan, Shandong, China, 250000
        • Not yet recruiting
        • Qilu Hospital of Shandong University
        • Contact:
      • Zibo, Shandong, China, 255020
        • Not yet recruiting
        • Zibo Central Hospital
        • Contact:
    • Shanghai
      • Shanghai, Shanghai, China, 200080
        • Recruiting
        • Shanghai General Hospital
        • Contact:
    • Shanxi
      • Taiyuan, Shanxi, China, 030001
        • Not yet recruiting
        • The First Hospital of Shanxi Medical University
        • Contact:
      • Xi'an, Shanxi, China, 710048
        • Not yet recruiting
        • The Frist Affiliated Hospital of Xi'an Jiaotong University
        • Contact:
    • Sichuan
      • Chengdu, Sichuan, China, 610072
        • Not yet recruiting
        • Sichuan Provincial People's Hospital
        • Contact:
      • Chengdu, Sichuan, China, 610044
        • Not yet recruiting
        • West China Hospital of Sichuan University
        • Contact:
    • Tianjin
      • Tianjin, Tianjin, China, 300052
        • Not yet recruiting
        • Tianjin Medical University General Hospital
        • Contact:
      • Tianjin, Tianjin, China, 300190
        • Not yet recruiting
        • Tianjin First Central Hospital
        • Contact:
          • Hongmei Gao, Doctor
          • Phone Number: 1307225 6661
          • Email: ghm182@163.com
    • Xinjiang
      • Ürümqi, Xinjiang, China, 830054
        • Not yet recruiting
        • The first affiliated hospital of Xinjiang medical university
        • Contact:
    • Zhejiang
      • Ningbo, Zhejiang, China, 315020
        • Not yet recruiting
        • The Frist Affiliated Hospital of Ningbo University
        • Contact:
      • Taizhou, Zhejiang, China, 317000
        • Not yet recruiting
        • Taizhou Hospital of Zhejiang Province
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Angiotensin Ⅱ Injection
Angiotensin 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.
Drug: Angiotensin II Injection
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.
Placebo Comparator: Placebo
The 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.
Drug: 0.9% sodium chloride injection
0.9% sodium chloride injection, not containing active ingredients.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of subjects with blood pressure response at 3 hours after administration of study drug
Time Frame: 3 hours after dose
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Sequential Organ Failure Assessment (SOFA) total score
Time Frame: 48 hours after dose
Change from baseline in Sequential Organ Failure Assessment (SOFA) total score. The SOFA score evaluates organ failure according to the conditions of respiratory, blood, liver, cardiovascular, central nervous, kidney and other systems, is scored from 0 to 4, with a higher score representing more severe failure.
48 hours after dose
Cardiovascular SOFA subscore
Time Frame: 48 hours after dose
Change from baseline in Sequential Organ Failure Assessment (SOFA) subscore. The SOFA score evaluates organ failure according to the conditions of respiratory, blood, liver, cardiovascular, central nervous, kidney and other systems, is scored from 0 to 4, with a higher score representing more severe failure.
48 hours after dose
Mortality at Day 7
Time Frame: Day 7 after dose
All-cause mortality of subject at Day 7
Day 7 after dose
Mortality at Day 28
Time Frame: Day 28 after dose
All-cause mortality of subject at Day 28
Day 28 after dose
Proportion of subjects with blood pressure response at 1 hour after administration
Time Frame: 1 hour after dose
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
1 hour after dose
Proportion of subjects with blood pressure response at 2 hours after administration
Time Frame: 2 hours after dose
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
2 hours after dose
Change in background vasoactive agent dose from 0 to 48 hours
Time Frame: 48 hours after dose
Change in background vasoactive dose from baseline to 48 hours after dose
48 hours after dose
Absolute change in blood lactate from 0 to 3 hours
Time Frame: 3 hours after dose
Absolute change in blood lactate from 0 to 3 hours
3 hours after dose
Absolute change in blood lactate from 3 to 48 hours
Time Frame: 3 to 48 hours after dose
Absolute change in blood lactate from 3 to 48 hours
3 to 48 hours after dose
Absolute change in heart rate from 0 to 3 hours
Time Frame: 3 hours after dose
Absolute change in heart rate from 0 to 3 hours
3 hours after dose
Absolute change in heart rate from 3 to 48 hours
Time Frame: 3 to 48 hours after dose
Absolute change in heart rate from 3 to 48 hours
3 to 48 hours after dose
Adverse events (AE)
Time Frame: From drug administration to the end of the study, a total of 28 days
Incidence and severity of adverse events (AE)
From drug administration to the end of the study, a total of 28 days
Serious adverse events (SAE)
Time Frame: From drug administration to the end of the study, a total of 28 days
Incidence and severity of serious adverse events (SAE)
From drug administration to the end of the study, a total of 28 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 23, 2024

Primary Completion (Estimated)

June 1, 2027

Study Completion (Estimated)

December 1, 2027

Study Registration Dates

First Submitted

April 2, 2024

First Submitted That Met QC Criteria

April 2, 2024

First Posted (Actual)

April 8, 2024

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

January 21, 2025

Last Verified

April 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TQG3902-III-01

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Vasodilatory Shock

Clinical Trials on Angiotensin II Injection

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Madagascar

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe