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

CTTQ

Status and phase: Enrolling; Phase 3

Conditions: Vasodilatory Shock

Treatments: Drug: 0.9% sodium chloride injection; Drug: Angiotensin II Injection

Study type: Interventional

Funder types: Industry

Identifiers

NCT06351150

TQG3902-III-01

Details and patient eligibility

About

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.

Enrollment: 214 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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214 participants in 2 patient groups, including a placebo group

Angiotensin Ⅱ Injection

Experimental group

Description:

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.

Treatment:

Drug: Angiotensin II Injection

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: 0.9% sodium chloride injection