Terlipressin Alone Versus the Standard Therapy With Catecholamines for Hepatic Patients With Septic Shock- Prospective Single Center Randomized Controlled Study.

The purpose of this study is to evaluate the use of terlipressin compared to standard regimen in hepatic patients with septic shock. Another aim is to compare the mortality rate & the effects on renal functions in both groups.

Study Overview

• Status: Unknown
• Conditions: Resolution of Septic Shock With Terlipressin
• Intervention / Treatment: Drug: Experimental

Detailed Description

Study type:

This is a single center, prospective randomized controlled study.

Inclusion criteria:

The subjects are adults aged between 18 & 70 years who will be admitted to the intensive care unit (ICU) of National Hepatology & Tropical Medicine Research Institute (NHTMRI).

All patients that will be included in the study should have septic shock diagnosed by having sepsis with an underlying circulatory and cellular/metabolic abnormality

Exclusion criteria:

Patients will be excluded if they are pregnant, have uncontrolled hypertension, ischemic skin necrosis, present or suspected coronary artery disease, present or suspected acute mesenteric ischemia, or peripheral vascular diseases (e.g. Raynaud's syndrome or related diseases) or hypersensitivity to terlipressin.

Study design:

Fifty patients will be enrolled in each arm of the study & randomly assigned in a 1:1 manner to receive either intravenous infusion (IVi) terlipressin by rate 1-2µg/kg/min. or intravenous infusion norepinephrine in an initial dose of 0.01µg/kg/min which can be increased every 15-30min. to 3µg/kg/min. maximum ± epinephrine with an initial dose 0.05µg/kg/min. IVi & can be titrated every 15-30min. The increments of epinephrine dose will be 0.05- 0.2µg/kg/min. and up to 2µg/Kg/min. The end point of the study will be achieving mean arterial pressure ≥ 65mmHg & normalized lactate ≤ 2mmol/L or lactate clearance ≥ 10% within 6hours All demographic data will be obtained at time of admission, including the patients' age, sex, body mass index (BMI), associated co-morbidities (diabetes mellitus, hypertension), Child-Pugh score and Sequential Organ Failure Assessment (SOFA).

Vital signs including the heart rate, mean arterial pressure (MAP) through arterial cannula, central venous pressure (CVP) through a catheter inserted either in the internal jugular vein or the subclavian vein will be measured at admission and at regular intervals. The volume & fluid balance will be recorded at admission and then will be followed up daily and recorded as required. Daily ECG with ST analysis, lactate level & ScVO2 will be measured on admission and then recorded at regular intervals during treatment after 2, 6, 12, 24 & 48hours.

Organ dysfunction and injury (aspartate aminotransferase, alanine amino-transaminase, total bilirubin, international normalized ratio, serum creatinine and troponin-I) will be analyzed at admission, and after 12, 24 & 48hours of treatment.

The rate of norepinephrine ± epinephrine infusion as well as terlipressin dose required to keep MAP at 65 mmHg will be recorded at baseline and 6, 12, 24, and 48hours after treatment.

Twenty-eight day mortality will be followed by phone calls to the patient or one of his/her first-degree relatives.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt, 11441
    • Recruiting
    • NHTMRI
    • Contact: Eman El-Desoki, Ph D; Phone Number: 01227409501; Email: eman18350@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adults aged between 18 & 70years who will be admitted to the intensive care unit (ICU) of National Hepatology & Tropical Medicine Research Institute (NHTMRI).

All patients that will be included in the study should have septic shock diagnosed by having sepsis with an underlying circulatory and cellular/metabolic abnormality.

Exclusion Criteria:

• Patients will be excluded if they are pregnant, have uncontrolled hypertension, ischemic skin necrosis, present or suspected coronary artery disease, present or suspected acute mesenteric ischemia, or peripheral vascular diseases (e.g. Raynaud's syndrome or related diseases) and hypersensitivity to Terlipressin.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: nor-epinephrine+/- epinephrine infusion; Intravenous infusion of Nor-epinephrine in an initial dose of 0.01µg/kg/min. which can be increased every 15-30 minutes to maximum 3µg/kg/min. ± intravenous infusion of epinephrine with an initial dose 0.05µg/kg/min. & can be titrated every 15-30 minutes up to 2µg/Kg/min. The end point is to achieve mean arterial pressure ≥ 65 mmHg & normalized lactate ≤ 2 mmol/L or lactate clearance ≥ 10% within 6 hours. Patients will be followed for 48 hours.	Drug: Experimental; Patients in this arm of the study will receive intravenous infusion (IVi) terlipressin by rate 1-2µg/kg/min.; Other Names: Terlipressin intravenous infusion
OTHER: Terlipressin infusion; Intravenous infusion of terlipressin by rate 1-2µg/kg/min. The end point is to achieve mean arterial pressure ≥ 65 mmHg & normalized lactate ≤ 2mmol/L or lactate clearance ≥ 10% within 6 hours. Patients will be followed for 48 hours.	Drug: Experimental; Patients in this arm of the study will receive intravenous infusion (IVi) terlipressin by rate 1-2µg/kg/min.; Other Names: Terlipressin intravenous infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hemodynamic stability & optimization; mean blood pressure more than or equal 65mmHg	how fast hemodynamic stability will be achieved in each arm of the study	48hours up to 7days
mortality	28-day mortality will be followed by phone calls to the patient or one of his/her first degree relatives	28 days
Hemodynamic stability & optimization; mean blood pressure	for how long hemodynamic stability will be maintained	48hours up to 7days
Hemodynamic stability & optimization, lactate clearance to be 2mmol/L	how fast it will be achieved	48hours up to 7days

Collaborators and Investigators

• Sponsor: National Hepatology & Tropical Medicine Research Institute

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 1, 2018
• Primary Completion (ANTICIPATED): July 1, 2020
• Study Completion (ANTICIPATED): December 1, 2020

Study Registration Dates

• First Submitted: July 12, 2018
• First Submitted That Met QC Criteria: July 23, 2018
• First Posted (ACTUAL): August 1, 2018

Study Record Updates

• Last Update Posted (ACTUAL): August 6, 2018
• Last Update Submitted That Met QC Criteria: August 2, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Shock, Septic; Shock; Antihypertensive Agents; Vasoconstrictor Agents; Terlipressin
• Other Study ID Numbers: NHTMRI-ICU-B

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes