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

NCT ID: NCT03336814

Last Updated: 2018-11-29

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-07-27
• Study Completion Date: 2019-06-01

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.

Conditions

Septic Shock

Study Design

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

Study Groups

terlipressin associated with norepinephrine

Group Type: EXPERIMENTAL

Terlipressin

Intervention Type: DRUG

Administration of terlipressine

placebo (physiologic serum) associated with norepinephrine

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Administration of placebo

Interventions

Terlipressin

Administration of terlipressine

Intervention Type: DRUG

Placebo

Administration of placebo

Intervention Type: OTHER

Eligibility Criteria

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

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

Sponsors

Assistance Publique Hopitaux De Marseille

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jean-Olivier ARNAUD

Role: STUDY_DIRECTOR

Assistance Publique Hôpitaux de Marseille

Locations

Assistance Publique - Hôpitaux de Marseille

Marseille, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Gary Duclos

Role: CONTACT

gary.duclos@ap-hm.fr

Camille Delannoy

Role: CONTACT

drci@ap-hm.fr

0491382747 ext. +33

Facility Contacts

Duclos Gary

Role: primary

gary.duclos@ap-hm.fr

Other Identifiers

2017-000441-43

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2017-07

Identifier Type: -

Identifier Source: org_study_id