Angiotensin II for Distributive Shock

Distributive Shock Clinical Trial

Official title:

Angiotensin II as a First-line Vasopressor for Distributive Shock During or After Heart Transplantation or Durable Left Ventricular Assist Device Implantation: A Pilot Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04904562
• Other study ID #: STU00211528
• Status: Recruiting
• Phase: Phase 4
• Start date: June 1, 2022
• Est. completion date: December 31, 2024

Study information

• Verified date: November 2023
• Source: Northwestern University
• Contact: Choy Lewis, MD
• Phone: 312-926-5589
• Email: Choy.Lewis[@]nm.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a single-center, randomized, double-blind, placebo-controlled pilot study. A total of 40 patients who develop distributive shock, intra-operatively or post-operatively within 48 hours of heart transplant or left ventricular assist device placement will be enrolled. Participants will be randomized to Angiotensin II (Giapreza) vs. placebo plus standard of care, as a first line agent for vasoplegia. Two groups of patients will be enrolled:

• Group A: Heart Transplant (10 control, 10 treatment)

• Group B: LVAD implant (10 control, 10 treatment)

Description:

Patients undergoing implantation of a durable left ventricular assist devices (LVAD) or a heart transplantation are at increased risk for cardiac vasoplegia. Vasoplegia, during or following cardiac surgery, is a life-threatening condition that is characterized by poor organ perfusion and may progress to multi-organ failure. The prognosis is especially poor for patients with refractory hypotension, despite high doses of vasopressors. Existing data point to total catecholamine dose, cumulative time spent with hypotension, volume overload, need for blood transfusion as contributing factors. Catecholamine vasopressors and vasopressin, which are often used as first line vasopressor therapy, are also independent risk factors for end organ dysfunction. Data comparing mortality with the use of different classes of vasopressors, in various types of shock, have been equivocal to date. In addition, data comparing the use of different classes of vasopressors for vasoplegia during or after heart transplantation and LVAD implantation are lacking. In patients with distributive shock in the intensive care unit, angiotensin II has been shown to reduce total catecholamine dose over 24 hours and the cumulative time spent with hypotension. This study will evaluate, as the primary endpoint, whether first line use of angiotensin II affects total catecholamine vasopressor dose in the first 24 hours after vasoplegia is first. Secondary endpoints include cumulative time spent with mean arterial pressure < 70 mmHg within the first 24 hours after distributive shock is first diagnosed, need for vasoplegia rescue therapies (methylene blue, vitamin B12, Vitamin C, steroids), incidence of acute kidney injury and stroke, time to extubation, incidence of new tachyarrhythmias, need for blood transfusion and fluid overload within the first 24 hours, ICU and hospital length of stay, 30-day mortality and allograft rejection (for heart transplant recipients).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: December 31, 2024
• Est. primary completion date: June 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Patients (18 years of age or older)

2. Onset of distributive shock within 48 hours after heart transplantation or VAD placement. Distributive shock defined as MAP less than 55mmHg on CPB, MAP less than 70mmHg before or after CPB, or systemic vascular resistance (SVR) less than 800 dynes/cm/sec5 with cardiac index (CI) greater than 2.0L/min/m2 and clinically determined euvolemia.

Exclusion Criteria:

1. Patients without distributive shock,

2. Women who are pregnant or breastfeeding.

3. Patients who do not receive the study drug as a first line agent for distributive shock

4. Allergy to angiotensin II, angiotensin II or another vasopressor being used at the time of presentation to the operating room

5. Preexisting distributive shock

6. Preexisting thromboembolic disease

7. Patients who are unwilling to provide consent

Related Conditions & MeSH terms

• Distributive Shock
• Shock

Intervention

Drug:
• Angiotensin II
Angiotensin II started at 5 ng/kg/min and titrated in 5-10 ng/kg/min increments every 5 minutes up to 80ng/kg/min to achieve target arterial pressure (MAP)
• Placebo
Placebo

Locations

Country	Name	City	State
United States	Northwestern University	Chicago	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
Northwestern University	La Jolla Pharmaceutical Company

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Total catecholamine dose	Total catecholamine dose for first 24 hours after distributive shock is first diagnosed	24 hours
Secondary	Cumulative time spent with MAP < 70 mmHg	Cumulative time spent with MAP < 70 mmHg within the first 24 hours after distributive shock is first diagnosed	24 hours
Secondary	Time to extubation	Time to extubation after arrival in the ICU if distributive shock is diagnosed intraoperatively or time to extubation after distributive shock is diagnosed postoperatively	24 hours
Secondary	Incidence of stroke	Incidence of stroke confirmed by neurologist within 48 hours after distributive shock is first diagnosed	48 hours
Secondary	Incidence of acute kidney injury	Incidence of acute kidney injury, staged by KDIGO Creatinine criteria, within 48 hours after distributive shock is first diagnosed	48 hours
Secondary	Incidence of new tachyarrhythmia	Incidence of new tachyarrhythmia within the first 24 hours after distributive shock is first diagnosed	24 hours
Secondary	Units of blood transfused	Units of blood transfused within first 24 hours after distributive shock is first diagnosed	24 hours
Secondary	Fluid overload	Fluid overload within the first 24 hours after distributive shock is first diagnosed	24 hours
Secondary	Intensive care unit (ICU) length of stay	Total time spent in the ICU after initial diagnosis of distributive shock	1 year
Secondary	Hospital length of stay	Total time spent in the hospital after diagnosis of distributive shock	1 year
Secondary	30-day mortality	Subject death within 30 days of diagnosis of distributive shock	30 days