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

Phase 4

• Conditions: Septic Shock
• Interventions: Other: Placebo; Drug: Terlipressin

• Registration Number: NCT03336814
• Lead Sponsor: Assistance Publique Hopitaux De Marseille

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2017-11
• Study First Submitted: 2017-11-06
• Study First Submitted QC: 2017-11-06
• Study First Posted: 2017-11-08
• Study Start: 2018-07-27
• Last Update Submitted: 2018-11-28
• Last Update Posted: 2018-11-29
• Primary Completion: 2018-12-01
• Study Completion: 2019-06-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 40

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
placebo (physiologic serum) associated with norepinephrine	Placebo	-
terlipressin associated with norepinephrine	Terlipressin	-

Primary Outcome Measures

Name	Time	Method
Sequential Organ Failure Assessment (SOFA) score difference between the groups	Day 3

Secondary Outcome Measures

Name	Time	Method
Mortality rate	Day 28
Lactates clearance	48 hours

Trial Locations

Locations (1)

Assistance Publique - Hôpitaux de Marseille; 🇫🇷 Marseille Cedex 05, France