Clinical trial NCT03302650: Angiotensin II for Septic Shock Treatment
Official title: Angiotensin II for Septic Shock Treatment: Effects On Macro- and Microcirculation A Randomized, Controlled Pilot Trial (ANGSTROM Trial)
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: PHASE3
Conditions: Septic Shock
Lead sponsor: Cairo University
Sponsor class: OTHER
First posted: 2017-10-05
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Mean flow index
timeFrame: 6 Hours
Secondary outcomes:
measure: Proportion of perfused vessels
timeFrame: 6 Hours
measure: Perfused vessel density
timeFrame: 6 Hours
measure: systolic blood pressure
timeFrame: 6 hours
measure: Diastolic blood pressure
timeFrame: 6 hours
measure: Heart rate
timeFrame: 6 hours
measure: Serum lactate
timeFrame: 6 hours
measure: Urine output
timeFrame: 6 hours
measure: Serum Creatinine
timeFrame: 24 hours
measure: Serum Sodium
timeFrame: 24 hours
measure: Serum potassium
timeFrame: 24 hours
measure: Cardiac output
timeFrame: 6 hours
measure: systemic vascular resistance
timeFrame: 6 hours
measure: Norepinephrine requirements
timeFrame: 6 hours
measure: perfusion index
timeFrame: 6 hours
measure: total fluid intake
timeFrame: 24 hours
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: Cairo University
Study officials:
affiliation: Head of research committee section in anesthesia department
name: Ahmed Mukhtar, Professor
role: STUDY_DIRECTOR
affiliation: Department of critical care, University of London college hospital
name: Martin W Dünser, Professor
role: STUDY_DIRECTOR
References: