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

Vasodilatory Shock Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06351150
• Other study ID #: TQG3902-III-01
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: May 2024
• Est. completion date: December 2027

Study information

• Verified date: April 2024
• Source: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
• Contact: Xiangdong Guan, M.D.
• Phone: 13802925067
• Email: guanxiangdong1962[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 214
• Est. completion date: December 2027
• Est. primary completion date: June 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Shock
• Vasodilatory Shock

Intervention

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.
• 0.9% sodium chloride injection
0.9% sodium chloride injection, not containing active ingredients.

Locations

Country	Name	City	State
China	The Affiliated Hospital of Hebei University	Baoding	Hebei
China	Peking Union Medical College Hospital	Beijing	Beijing
China	The First Affiliated Hospital of Bengbu Medical College	Bengbu	Henan
China	Xiangya Hospital Central South University	Changsha	Hunan
China	Sichuan Provincial People's Hospital	Chengdu	Sichuan
China	West China Hospital of Sichuan University	Chengdu	Sichuan
China	The First Affiliated Hospital of Sun Yat sen University	Guangzhou	Guangdong
China	Zhujiang Hospital of Southern Medical University	Guangzhou	Guangdong
China	The First Affiliated Hospital of Harbin Medical University	Harbin	Heilongjiang
China	Liuzhou General Hospital	Liuzhou	Guangxi
China	The First Affiliated Hospital of Henan University of Science and Technology	Luoyang	Henan
China	Jiangsu Province Hospital	Nanjing	Jiangsu
China	Qingyuan Hospital Affiliated to Guangzhou Medical University	Qingyuan	Guangdong
China	The First Affiliated Hospital of Shantou University Medical College	Shantou	Guangdong
China	The First Hospital of Shanxi Medical University	Taiyuan	Shanxi
China	The First Affiliated Hospital of Xinjiang Medical University	Ürümqi	Xinjiang
China	Union Hospital, Tongji Medical College of huazhong university of science and technology	Wuhan	Hubei
China	The Second Affiliated Hospital of Xi'an Jiaotong University	Xi'an	Shaanxi
China	The First Affiliated Hospital of Zhengzhou University	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Sequential Organ Failure Assessment (SOFA) total score	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
Secondary	Cardiovascular SOFA subscore	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
Secondary	Mortality at Day 7	All-cause mortality of subject at Day 7	Day 7 after dose
Secondary	Mortality at Day 28	All-cause mortality of subject at Day 28	Day 28 after dose
Secondary	Proportion of subjects with blood pressure response at 1 hour after administration	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
Secondary	Proportion of subjects with blood pressure response at 2 hours after administration	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
Secondary	Change in background vasoactive agent dose from 0 to 48 hours	Change in background vasoactive dose from baseline to 48 hours after dose	48 hours after dose
Secondary	Absolute change in blood lactate from 0 to 3 hours	Absolute change in blood lactate from 0 to 3 hours	3 hours after dose
Secondary	Absolute change in blood lactate from 3 to 48 hours	Absolute change in blood lactate from 3 to 48 hours	3 to 48 hours after dose
Secondary	Absolute change in heart rate from 0 to 3 hours	Absolute change in heart rate from 0 to 3 hours	3 hours after dose
Secondary	Absolute change in heart rate from 3 to 48 hours	Absolute change in heart rate from 3 to 48 hours	3 to 48 hours after dose
Secondary	Adverse events (AE)	Incidence and severity of adverse events (AE)	From drug administration to the end of the study, a total of 28 days
Secondary	Serious adverse events (SAE)	Incidence and severity of serious adverse events (SAE)	From drug administration to the end of the study, a total of 28 days