Angiotensin II for Septic Shock Treatment

NCT ID: NCT03302650

Last Updated: 2019-01-16

Basic Information

• Recruitment Status: SUSPENDED
• Clinical Phase: PHASE3
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-04-01
• Study Completion Date: 2019-08-15

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.

Conditions

Septic Shock

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Angiotensin group

Patients will receive Angiotensin II at a starting dose of 20 ng/Kg/min. During the first 30 minutes after randomization, the angiotensin II infusion will be titrated to achieve a mean arterial pressure of 65-75 mmHg while the norepinephrine infusion will be withdrawn and stopped. Following a stabilization of 60 minutes, the angiotensin II infusion is titrated to achieve a mean arterial pressure of 85-95 mmHg. Following a 30 minutes wash-in period and a 60 minutes stabilization period, a third set of measurements will be taken. Then, the angiotensin II infusion will be withdrawn in small steps and replaced by a norepinephrine infusion which will then be titrated to achieve a mean arterial pressure of 65-75 mmHg. Then, the final set of measurements will be taken.

Group Type: EXPERIMENTAL

Angiotensin II

Intervention Type: DRUG

Patients will receive angiotensin-II at a starting dose of 20 ng/Kg/min.

Norepinephrine

Intervention Type: DRUG

patients will receive norepinephrine infusion adjusted according to blood pressure

Normal saline group

Patients will receive normal saline infusion in addition to norepinephrine infusion. The same mean arterial pressure levels (65-75 mmHg \> 85-95 mmHg \> 65-75 mmHg) will be achieved by titration of the norepinephrine infusion. Identical wash-in and stabilization periods will be kept as in the study group. Measurements will be taken at the same time points as in the study group. The maximum dose of norepinephrine applied will be 0.7 mcg/kg/min.

Group Type: PLACEBO_COMPARATOR

Normal saline

Intervention Type: DRUG

Patients will receive normal saline.

Norepinephrine

Intervention Type: DRUG

patients will receive norepinephrine infusion adjusted according to blood pressure

Interventions

Angiotensin II

Patients will receive angiotensin-II at a starting dose of 20 ng/Kg/min.

Intervention Type: DRUG

Normal saline

Patients will receive normal saline.

Intervention Type: DRUG

Norepinephrine

patients will receive norepinephrine infusion adjusted according to blood pressure

Intervention Type: DRUG

Other Intervention Names

Noradrenaline

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cairo University

OTHER

Sponsor Role: lead

Responsible Party

Ahmed Hasanin

Assistant professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ahmed Mukhtar, Professor

Role: STUDY_DIRECTOR

Head of research committee section in anesthesia department

Martin W Dünser, Professor

Role: STUDY_DIRECTOR

Department of critical care, University of London college hospital

Locations

Cairo University

Cairo, , Egypt

Countries

Egypt

Other Identifiers

N-68-2017

Identifier Type: -

Identifier Source: org_study_id