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

Septic Shock Clinical Trial

— TERLINOR  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03336814
• Other study ID #: 2017-07
• Secondary ID: 2017-000441-43
• Status: Recruiting
• Phase: Phase 4
• Start date: July 27, 2018
• Est. completion date: June 1, 2019

Study information

• Verified date: November 2017
• Source: Assistance Publique Hopitaux De Marseille
• Contact: Gary Duclos
• Email: gary.duclos[@]ap-hm.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: June 1, 2019
• Est. primary completion date: December 1, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Septic Shock
• Shock
• Shock, Septic

Intervention

Drug:
• Terlipressin
Administration of terlipressine

Other:
• Placebo
Administration of placebo

Locations

Country	Name	City	State
France	Assistance Publique - Hôpitaux de Marseille	Marseille Cedex 05

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique Hopitaux De Marseille

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sequential Organ Failure Assessment (SOFA) score difference between the groups		Day 3
Secondary	Mortality rate		Day 28
Secondary	Lactates clearance		48 hours