Clinical trial NCT03336814: Evaluation of Early Association of Terlipressin and Norepinephrine During Septic Shock; the TerliNor Study
Official title: Evaluation of Early Association of Terlipressin and Norepinephrine During Septic Shock; the TerliNor Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Septic Shock
Keywords: Terlipressin
norepinephrine
Lead sponsor: Assistance Publique Hopitaux De Marseille
Sponsor class: OTHER
First posted: 2017-11-08
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Sequential Organ Failure Assessment (SOFA) score difference between the groups
timeFrame: Day 3
Secondary outcomes:
measure: Mortality rate
timeFrame: Day 28
measure: Lactates clearance
timeFrame: 48 hours
Other outcomes:
Locations:
city: Marseille Cedex 05
country: France
facility: Assistance Publique - Hôpitaux de Marseille
Study officials:
affiliation: Assistance Publique Hôpitaux de Marseille
name: Jean-Olivier ARNAUD
role: STUDY_DIRECTOR
References: