Clinical trial NCT04904562: Angiotensin II for Distributive Shock
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Distributive Shock
Keywords: Vasoplegia
Lead sponsor: Northwestern University
Sponsor class: OTHER
Collaborators: name: La Jolla Pharmaceutical Company
First posted: 2021-05-27
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 1:1 randomization to receive either study drug or placebo
Primary purpose: PREVENTION

Brief 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)

Detailed 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).

Eligibility criteria: 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

Primary outcomes:
measure: Total catecholamine dose
timeFrame: 24 hours
Secondary outcomes:
measure: Cumulative time spent with MAP < 70 mmHg
timeFrame: 24 hours
measure: Time to extubation
timeFrame: 24 hours
measure: Incidence of stroke
timeFrame: 48 hours
measure: Incidence of acute kidney injury
timeFrame: 48 hours
measure: Incidence of new tachyarrhythmia
timeFrame: 24 hours
measure: Units of blood transfused
timeFrame: 24 hours
measure: Fluid overload
timeFrame: 24 hours
measure: Intensive care unit (ICU) length of stay
timeFrame: 1 year
measure: Hospital length of stay
timeFrame: 1 year
measure: 30-day mortality
timeFrame: 30 days
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
Study officials:
affiliation: Northwestern University
name: Choy Lewis, MD
role: PRINCIPAL_INVESTIGATOR
References: