Evaluation of Early Association of Terlipressin and Norepinephrine During Septic Shock; the TerliNor Study (TERLINOR)

In guidelines norepinephrine is the first line vasopressor recommended in case of septic shock. Use of vasopressin is recommended when norepinephrine fails to maintain a mean arterial pressure above 65mmHg or in salvage. Several studies failed to show a superiority of vasopressin over norepinephrine but none evaluated the effect of an early association on organ failure. Terlipressin is a pro-drug of vasopressin which has the same vasoconstrictor effect. We hypothesize that the early association of terlipressin and norepinephrine during septic shock reduces organ failure.

This bi centric, double-blinded, randomised, controlled versus placebo study includes 40 patients. Randomisation will be stratified between centers (two university affiliated intensive care units of Assistance-Publique-Hôpitaux de Marseille, Marseille, France). All patients with septic shock needing more than 0,5µg/kg/min of norepinephrine to reach PAM objectives are randomised, after hemodynamic evaluation and optimisation, to receive continuous infusions of terlipressin (0,01mg/kg/min) or placebo (physiologic serum). The 2 groups receive steroid therapy (continuous intravenous hydrocortisone perfusion) at this time. Clinicians are blinded of perfusion used. Use of terlipressin remains possible in salvage when patients need more of 1µg/kg/min of norepinephrine on physician's decision. Patients with acute ischemic or septic heart failure are excluded of the study.

Primary objective is sepsis related Sequential Organ Failure Assessment (SOFA) score difference between the groups at day 3. Secondary objectives are mortality at day 28, lactates clearance in the first 48hours, renal function (evaluates with AKIN criteria) and use of renal replacement therapy.

Study Overview

• Status: Unknown
• Conditions: Septic Shock
• Intervention / Treatment: Other: Placebo; Drug: Terlipressin

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Marseille Cedex 05, France, 13354
    • Recruiting
    • Assistance Publique - Hopitaux de Marseille
    • Contact: Duclos Gary; Email: gary.duclos@ap-hm.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Older than 18 years
• Dose of norepinephrine greater than 0.3 μg / kg / min
• Lactate greater than 2.0 mmol / l

Exclusion Criteria:

• A left heart failure objectified in ultrasound transthoracique by a fraction of left(awkward) ejection of the ventricle lower than 30 % either by thermodilution transpulmonaire with a cardiac index lower than 2,5 l / min / m2 after optimization of the volémie or a central venous saturation in oxygen ( SVcO2) lower than 60 % after optimization of the blood volume.
• Minors
• Pregnant
• Not having terlipressin allergy
• Not having excipient allergy
• A history known for recent acute coronary syndrome (< 3mois)
• An acute coronary syndrome defined by an increase of the troponine and a rise of the segment ST in the electrocardiogram

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: terlipressin associated with norepinephrine	Drug: Terlipressin; Administration of terlipressine
Placebo Comparator: placebo (physiologic serum) associated with norepinephrine	Other: Placebo; Administration of placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Sequential Organ Failure Assessment (SOFA) score difference between the groups	Day 3

Secondary Outcome Measures

Outcome Measure	Time Frame
Mortality rate	Day 28
Lactates clearance	48 hours

Collaborators and Investigators

• Sponsor: Assistance Publique Hopitaux De Marseille

Study record dates

Study Major Dates

• Study Start (Actual): July 27, 2018
• Primary Completion (Anticipated): December 1, 2018
• Study Completion (Anticipated): June 1, 2019

Study Registration Dates

• First Submitted: November 6, 2017
• First Submitted That Met QC Criteria: November 6, 2017
• First Posted (Actual): November 8, 2017

Study Record Updates

• Last Update Posted (Actual): November 29, 2018
• Last Update Submitted That Met QC Criteria: November 28, 2018
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: norepinephrine; Terlipressin
• 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: 2017-07; 2017-000441-43 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No