Angiotensin II for Distributive Shock

Northwestern University

Status and phase: Enrolling; Phase 4

Conditions: Distributive Shock

Treatments: Drug: Angiotensin II; Drug: Placebo

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT04904562

STU00211528

Details and patient eligibility

About

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)

Full 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).

Enrollment: 40 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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40 participants in 2 patient groups, including a placebo group

Treatment

Active Comparator group

Description:

Angiotensin II administered as an intravenous (IV) infusion will be increased every 5 minutes by 5-10ng/kg/min increments up to 80ng/kg/min

Treatment:

Drug: Angiotensin II

Control

Placebo Comparator group

Description:

Intravenous (IV) infusion (saline)

Treatment:

Drug: Placebo