Angiotensin II for Septic Shock Treatment

NCT03302650 | Suspended Phase 3 DMC

• 1 other identifier: N-68-2017
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Septic Shock

Outcome Measures

Primary Outcomes (1)

• 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 ųm.

  6 Hours

Secondary Outcomes (15)

• Proportion of perfused vessels

  6 Hours

• Perfused vessel density

  6 Hours

• systolic blood pressure

  6 hours

• Diastolic blood pressure

  6 hours

• Heart rate

  6 hours

Study Arms (2)

Angiotensin group

EXPERIMENTAL

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infusion will be titrated to achieve a mean arterial pressure of 65-75 mmHg while the norepinephrine infusion will be withdrawn and stopped.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 Then, the angiotensin II infusion will be withdrawn in small steps and replaced by a norepinephrine infusion which will then be titrated to achieve a mean arterial pressure of 65-75 mmHg.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.

Drug: Angiotensin II; Drug: Norepinephrine

Normal saline group

PLACEBO COMPARATOR

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.

Drug: Normal saline; Drug: Norepinephrine

Interventions

Angiotensin II DRUG

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

Angiotensin group

Normal saline DRUG

Patients will receive normal saline.

Normal saline group

Norepinephrine DRUG

patients will receive norepinephrine infusion adjusted according to blood pressure

Also known as: Noradrenaline

Angiotensin group; Normal saline group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• Acute coronary syndrome.
• Impaired cardiac contractility
• Bronchospasm.
• Major burns
• Liver failure.
• Active bleeding.

Sponsors & Collaborators

• Cairo University: lead

Study Sites (1)

Cairo University

Cairo, Egypt

Location

MeSH Terms

Conditions

Shock, Septic

Interventions

Angiotensin II; Saline Solution; Norepinephrine

Condition Hierarchy (Ancestors)

Sepsis; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Intervention Hierarchy (Ancestors)

Angiotensins; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Autacoids; Inflammation Mediators; Biological Factors; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Biogenic Monoamines; Biogenic Amines; Catecholamines; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

• Ahmed Mukhtar, Professor

  Head of research committee section in anesthesia department

  STUDY DIRECTOR

• Martin W Dünser, Professor

  Department of critical care, University of London college hospital

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant professor

Study Record Dates

• First Submitted: October 1, 2017
• First Posted: October 5, 2017
• Study Start: April 1, 2019
• Primary Completion: August 1, 2019
• Study Completion: August 15, 2019
• Last Updated: January 16, 2019

Record last verified: 2019-01

Locations

EG (1)