Angiotensin II Stress Test. Renin Kinetics During Treatment of Vasoplegic Shock With Angiotensin II in Relation to Hemodynamic Response to Treatment With Angiotensin II.
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Sponsor
- Enrollment
- 121
- Locations
- 4
- Primary Endpoint
- ICU free days
Study Overview
Brief Summary
Shock is a life-threatening condition which can cause multiple organ failure and even death. One characteristic of shock is low blood pressure which is managed with drugs called vasopressors. Most frequently used vasopressors are noradrenaline, vasopressin and recently also angiotensin II. Angiotensin II is present in the body and has a physiological role in maintaining blood pressure in healthy persons. Renin is an enzyme and a key factor in angiotensin II production in the body. In patients with shock, there is a lack of angiotensin II and an excess of renin in the body. Due to the literature renin has the potential to be a marker of severity of shock. Synthetic angiotensin II is used in patients with shock in whom we cannot normalize the blood pressure with noradrenaline and vasopressin. Regarding scientific data, the use of synthetic angiotensin II reduces the dose of noradrenaline and vasopressin and the incidence of acute kidney injury. The aim of our study is to find out what is the relation between the concentration of renin before and 6 hours after the start of using angiotensin II in patients with shock and their clinical outcome. Since not all patients with shock are responding to angiotensin II, the aim of our study is also to find out which patients could benefit most from synthetic angiotensin II.
Detailed Description
In patients with distributive shock (≥18 years) with noradrenaline at least 0,3 mcg/kg/min and vasopressin 0,03 IE/min not achieving an appropriate mean arterial pressure (65-85 mmHg) despite fluid resuscuitation an angiotensin II infusion will be started at 20 ng/kg/min and after that adjusted to a max dose of 40 ng/kg/min if needed. Before the infusion and 6 hours after the start of angiotensin II infusion a blood sample will be drawn to determine the renin concentration. The primary outcome will be organ failure free days and ICU free days. Secondary outcome will be the need for vasopressors, dialysis, mechanical ventilation, trend of renin concentration.
Study Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Prospective
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •patients with distributive shock lasting < 72 hours
- •a goal mean arterial pressure (65-85 mmHg) not achieved despite optimal fluid resuscitation (30 ml/kg cristalloid) and an infusion of at least noradrenaline 0.3 mcg/kg/min and vasopressin 0.03 IE/min
- •the patient did not get angiotensin II before
- •predicted survival is >24h
- •no limitations for active treatment
Exclusion Criteria
- •burns >20% body area
- •acute coronary syndrome
- •bronchospasm
- •liver disease (MELD ≥30)
- •severe acute bleeding (need for 4 or more units of concentrated erythrocyte)
- •acute mesenteric ischemia
- •aortic dissection
- •leucopenia <1000/mm3
- •pregnancy
- •Raynaud disease, systemic sclerosis, vasospastic disease
- •active venous or arterial thromboembolic disease
- •the need for daily dose of hydrocortisone 500 mg or more
- •cardiac index \70%
Outcomes
Primary Outcomes
ICU free days
Time Frame: 0-30 days
30 minus the number of days in the ICU
organ failure free days
Time Frame: 0-30 days
days alive without the need of vasopressors, ventilators, or dialysis
Association between 0-6-hour change in relative renin ratio (ΔRRR = RRR6h - RRR0h) and 28-day organ failure-free days (without vasopressors, mechanical ventilation and renal replacement therapy (RRT))
Time Frame: 0-28 days
days alive without the need of vasopressors, ventilators, or dialysis
Secondary Outcomes
- mechanical ventilation need(0-30 days)
- dyalisis need(0-30 days)
- renin trend(0-6 hours)
- duration of the need for vasopressors(0-30 days)
- Association between ΔRRR and 28-day ICU free days(0-28 days)
- Association between ΔRRR and vasopressor free days(0-28 days)
- Association between ΔRRR and cumulative dose of vasopressors expressed in norepinephrine equivalent dose (NED)(0-28 days)
- Association between ΔRRR and the RRT free days(0-28 days)
- Association between ΔRRR and invasive mechanical ventilation free days(0-28 days)
- Determination of responders and nonresponders based on calculation of the ratio between change in MAP between 0 and 1 hours of protocol to the change in total vasopressor NED between 0 and 1 hours of protocol.(0-1 hour)
- Comparison of the prognostic performance of renin and lactate at 0 and 6 hours for 28-day mortality.(0-6 hour)
- product ( [renin] x [lactate]) at baseline and 6 hours after start of angiotensin II infusion(baseline - just before start of angiotensin II infusion; 6 hours - 6 hours after start of angiotensin II infusion)
- Change in total norepinephrine-base dose equivalen (NED) at baseline and 1 hour predicts mortality(change in norepinephrine-base dose equivalent (NED) from start of angiotensin II infusion (baseline) and 1 hour after start of angiotensin II infusion)
Investigators
Andreja Möller Petrun, MD, PhD
Assoc. Prof. Andreja Möller Petrun, MD, PhD; Principal Investigator
University Medical Centre Maribor