Angiotensin II for Septic Shock Treatment

Septic Shock Clinical Trial

Official title:

Angiotensin II for Septic Shock Treatment: Effects On Macro- and Microcirculation A Randomized, Controlled Pilot Trial (ANGSTROM Trial)

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT03302650
• Other study ID #: N-68-2017
• Status: Suspended
• Phase: Phase 3
• Start date: April 1, 2019
• Est. completion date: August 15, 2019

Study information

• Verified date: January 2019
• Source: Cairo University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study aims to investigate the effect of angiotensin II on microcirculation and peripheral perfusion in patients with septic shock.

Description:

Shock is a syndrome characterized by acute circulatory failure resulting in impaired peripheral tissue perfusion. Distributive shock is the most common type of shock and is usually caused by severe sepsis. Distributive shock is characterized by profound vasodilatation leading to decreased arterial blood pressure and impaired organ perfusion despite high cardiac output.

The use of vasopressors is an essential management line for distributive sock. Two groups of vasopressors are usually used for management of shock: catecholamines and vasopressin-like peptides. There is a continuous need for other vasopressors because:

1- Available vasopressors have narrow therapeutic window. 2- Patients with severe hypotension refractory to the currently available classes usually die.

A third system is usually engaged in the physiology of shock which is Renin-Angiotensin—aldosterone system. Angiotensin II is a natural hormone which is a potent vasopressor; moreover, angiotensin II stimulates the production of both antidiuretic hormone and adrenocorticotropin hormone.

In a pilot study, angiotensin II was reported as an effective rescue vasopressor in septic shock patients on multiple vasopressors. Angiotensin II improved mean arterial pressure and helped in reduction of the doses of catecholamines. In a recent large randomized controlled trial, angiotensin II improved blood pressure in catecholamine-resistant distributive shock patients.

Microcirculation is the primary site of oxygen and nutrient exchange. Maintenance of microcirculatory perfusion is a prerequisite for preservation of organ function. Multiple organ failure is common in patients with distributive shock despite maintenance of parameters of global perfusion due to disrupted microcirculatory perfusion. Furthermore, restoration of microcirculatory perfusion was correlated with improvement in survival. This study aims to investigate the effect of angiotensin II on peripheral microcirculation in patients with septic shock.

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 20
• Est. completion date: August 15, 2019
• Est. primary completion date: August 1, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Septic shock patients.

• Aged above 18 years.

• With cardiac index > 2.4 L/min/BSA 1.73 m2.

• On high dose vasopressors (defined as norepinephrine infusion above 0.1 mcg/Kg/min)

Exclusion Criteria:

• Acute coronary syndrome.

• Impaired cardiac contractility

• Bronchospasm.

• Major burns

• Liver failure.

• Active bleeding.

Related Conditions & MeSH terms

• Septic Shock
• Shock
• Shock, Septic

Intervention

Drug:
• Angiotensin II
Patients will receive angiotensin-II at a starting dose of 20 ng/Kg/min.
• Normal saline
Patients will receive normal saline.
• Norepinephrine
patients will receive norepinephrine infusion adjusted according to blood pressure

Locations

Country	Name	City	State
Egypt	Cairo University	Cairo

Sponsors (1)

Lead Sponsor	Collaborator
Cairo University

Country where clinical trial is conducted

Egypt, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean flow index	Mean flow index measured by Side stream dark field imaging optical probe (Microscan; MicroVision Medical, Amsterdam, Netherlands). Briefly, after gentle cleansing of the tongue by isotonic-saline-drenched gauze, avoiding pressure artifacts, 5 steady images of at least 20 seconds each will be obtained and stored under a random number. Offline blind analysis of each video will be done using a dedicated software (Automated Vascular Analysis 3.0; Academic Medical Center, University of Amsterdam, The Netherlands).; The microvascular flow index (MFI) will be used to quantify microvascular blood flow. In this score, flow is characterized as absent (0), intermittent (1), sluggish (2), or normal (3), for each patient the values from 5 videos will be averaged. Since our investigation will be focused on small vessels, calculations will be separately performed for vessels with a diameter less than 20 um.	6 Hours
Secondary	Proportion of perfused vessels	Proportion of perfused vessels measured by Side stream dark field imaging optical probe (Microscan; MicroVision Medical, Amsterdam, Netherlands). Briefly, after gentle cleansing of the tongue by isotonic-saline-drenched gauze, avoiding pressure artifacts, 5 steady images of at least 20 seconds each will be obtained and stored under a random number. Offline blind analysis of each video will be done using a dedicated software (Automated Vascular Analysis 3.0; Academic Medical Center, University of Amsterdam, The Netherlands)	6 Hours
Secondary	Perfused vessel density	Perfused vessel density measured by Side stream dark field imaging optical probe (Microscan; MicroVision Medical, Amsterdam, Netherlands). Briefly, after gentle cleansing of the tongue by isotonic-saline-drenched gauze, avoiding pressure artifacts, 5 steady images of at least 20 seconds each will be obtained and stored under a random number. Offline blind analysis of each video will be done using a dedicated software (Automated Vascular Analysis 3.0; Academic Medical Center, University of Amsterdam, The Netherlands)	6 Hours
Secondary	systolic blood pressure	systolic blood pressure measured in mmHg	6 hours
Secondary	Diastolic blood pressure	diastolic blood pressure measured in mmHg	6 hours
Secondary	Heart rate	heart rate in beats per minute	6 hours
Secondary	Serum lactate	Serum lactate measured in milligrams per deciliter	6 hours
Secondary	Urine output	quantity of urine in milliliters	6 hours
Secondary	Serum Creatinine	serum creatinine measured in milligrams per deciliter	24 hours
Secondary	Serum Sodium	Serum sodium measured in milligrams per deciliter	24 hours
Secondary	Serum potassium	Serum potassium measured in milligrams per deciliter	24 hours
Secondary	Cardiac output	quantity of blood pumper by the heart measured by electrical cardiometry in liters per minute	6 hours
Secondary	systemic vascular resistance	systemic vascular resistance measured by electrical cardiometry	6 hours
Secondary	Norepinephrine requirements	total requirement of norepinephrine needed to maintain mean arterial blood pressure above 65 mmHg	6 hours
Secondary	perfusion index	proportion of pulsatile to non-pulsatile portions in peripheral circulation	6 hours
Secondary	total fluid intake	amount of fluids received by the patient in milliliters	24 hours