Using Angiotensin II to treat 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

This study is testing if an injection of angiotensin II can help people with severe shock who haven't improved with regular treatments.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 214 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd. (Industry-sponsored)
• Locations: 42 sites (Hefei, Anhui and 41 other locations)
• Trial ID: NCT06351150 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the efficacy and safety of angiotensin II injection compared to a placebo in patients suffering from refractory distributed shock. It is a randomized, double-blind, placebo-controlled study with a 1:1 randomization ratio, aiming to enroll a total of 214 participants. The study will assess the therapeutic outcomes based on the ability to maintain mean arterial pressure in patients who have not responded adequately to standard vasoactive drug treatments. Participants will receive either the angiotensin II injection or a sodium chloride placebo over a specified treatment period.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 75 diagnosed with refractory distributive shock who have been on vasoactive drugs and still have low mean arterial pressure.

Not a fit: Patients who do not have refractory distributive shock or are outside the age range of 18 to 75 may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve blood pressure management in patients with refractory distributed shock.

How similar studies have performed: Other studies have shown promising results with angiotensin II in similar contexts, suggesting potential for success in this approach.

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.

Where this trial is running

Hefei, Anhui and 41 other locations

• The Second People's Hospital of Hefei — Hefei, Anhui, China (Not_yet_recruiting)
• The Frist Affiliated Hospital of Wannan Medical College — Wuhu, Anhui, China (Not_yet_recruiting)
• Beijing Tiantan Hospital,Capital Medical University — Beijing, Beijing Municipality, China (Not_yet_recruiting)
• Peking Union Medical College Hospital — Beijing, Beijing Municipality, China (Not_yet_recruiting)
• The Frist Affiliated Hospital of Chongqing Medical University — Chongqing, Chongqing Municipality, China (Not_yet_recruiting)
• The people's Hospital of the University of traditional Chinese medicine in Fujian — Fuzhou, Fujian, China (Not_yet_recruiting)
• Gansu Provincial Hospital — Lanzhou, Gansu, China (Not_yet_recruiting)
• The First Affiliated Hospital of Sun Yat sen University — Guangzhou, Guangdong, China (Not_yet_recruiting)
• Zhujiang Hospital of Southern Medical University — Guangzhou, Guangdong, China (Not_yet_recruiting)
• The First Affiliated Hospital of Jinan University — Guangzhou, Guangdong, China (Not_yet_recruiting)
• Qingyuan Hospital Affiliated to Guangzhou Medical University — Qingyuan, Guangdong, China (Not_yet_recruiting)
• The First Affiliated Hospital of Shantou University Medical College — Shantou, Guangdong, China (Not_yet_recruiting)
• Peking University Shenzhen Hospital — Shenzhen, Guangdong, China (Not_yet_recruiting)
• The People's Hospital of Guangxi Zhuang Autonomous Region — Guilin, Guangxi, China (Not_yet_recruiting)
• Liuzhou General Hospital — Liuzhou, Guangxi, China (Not_yet_recruiting)
• The Affiliated Hospital of Guizhou Medical University — Guiyang, Guizhou, China (Not_yet_recruiting)
• The Affiliated Hospital of Hebei University — Baoding, Hebei, China (Not_yet_recruiting)
• The First Affiliated Hospital of Harbin Medical University — Harbin, Heilongjiang, China (Not_yet_recruiting)
• The First Affiliated Hospital of Bengbu Medical College — Bengbu, Henan, China (Not_yet_recruiting)
• The First Affiliated Hospital of Henan University of Science and Technology — Luoyang, Henan, China (Not_yet_recruiting)
• The First Affiliated Hospital of Zhengzhou University — Zhengzhou, Henan, China (Not_yet_recruiting)
• Union Hospital, Tongji Medical College of huazhong university of science and technology — Wuhan, Hubei, China (Not_yet_recruiting)
• Wuhan Third Hospital — Wuhan, Hubei, China (Not_yet_recruiting)
• Xiangya Hospital Central South University — Changsha, Hunan, China (Not_yet_recruiting)
• Hunan Provincial People's Hospital — Changsha, Hunan, China (Not_yet_recruiting)
• Jiangsu Province Hospital — Nanjing, Jiangsu, China (Not_yet_recruiting)
• Wuxi People's Hospital — Wuxi, Jiangsu, China (Not_yet_recruiting)
• The Frist Affiliated Hospital of Nanchang University — Nanchang, Jiangxi, China (Not_yet_recruiting)
• Shengjing Hospital of China Medical University — Shenyang, Liaoning, China (Not_yet_recruiting)
• The Second Affiliated Hospital of Xi'an Jiaotong University — Xi'an, Shaanxi, China (Not_yet_recruiting)
• Qilu Hospital of Shandong University — Jinan, Shandong, China (Not_yet_recruiting)
• Zibo Central Hospital — Zibo, Shandong, China (Not_yet_recruiting)
• Shanghai General Hospital — Shanghai, Shanghai Municipality, China (Recruiting)
• The First Hospital of Shanxi Medical University — Taiyuan, Shanxi, China (Not_yet_recruiting)
• The Frist Affiliated Hospital of Xi'an Jiaotong University — Xi’an, Shanxi, China (Not_yet_recruiting)
• West China Hospital of Sichuan University — Chengdu, Sichuan, China (Not_yet_recruiting)
• Sichuan Provincial People's Hospital — Chengdu, Sichuan, China (Not_yet_recruiting)
• Tianjin Medical University General Hospital — Tianjin, Tianjin Municipality, China (Not_yet_recruiting)
• Tianjin First Central Hospital — Tianjin, Tianjin Municipality, China (Not_yet_recruiting)
• The First Affiliated Hospital of Xinjiang Medical University — Ürümqi, Xinjiang, China (Not_yet_recruiting)
• The Frist Affiliated Hospital of Ningbo University — Ningbo, Zhejiang, China (Not_yet_recruiting)
• Taizhou hospital of Zhejiang Province — Taizhou, Zhejiang, China (Not_yet_recruiting)

Study contacts

• Study coordinator: Xiangdong Guan, M.D.

Conditions Vasodilatory Shock