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

NCT03336814 | Unknown Phase 4

• 2 other identifiers: 2017-072017-000441-43
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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

Keywords

Terlipressin; norepinephrine

Outcome Measures

Primary Outcomes (1)

• Sequential Organ Failure Assessment (SOFA) score difference between the groups

  Day 3

Secondary Outcomes (2)

• Mortality rate

  Day 28

• Lactates clearance

  48 hours

Study Arms (2)

terlipressin associated with norepinephrine

EXPERIMENTAL

Drug: Terlipressin

placebo (physiologic serum) associated with norepinephrine

PLACEBO COMPARATOR

Other: Placebo

Interventions

Terlipressin DRUG

Administration of terlipressine

terlipressin associated with norepinephrine

Placebo OTHER

Administration of placebo

placebo (physiologic serum) associated with norepinephrine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Assistance Publique Hopitaux De Marseille: lead

Study Sites (1)

Assistance Publique - Hôpitaux de Marseille

Marseille, 13354, France

RECRUITING

MeSH Terms

Conditions

Shock, Septic

Interventions

Terlipressin

Condition Hierarchy (Ancestors)

Sepsis; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Intervention Hierarchy (Ancestors)

Lypressin; Vasopressins; Pituitary Hormones, Posterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Study Officials

• Jean-Olivier ARNAUD

  Assistance Publique Hôpitaux de Marseille

  STUDY DIRECTOR

Central Study Contacts

Gary Duclos

CONTACT

gary.duclos@ap-hm.fr

Camille Delannoy

CONTACT

0491382747; drci@ap-hm.fr

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 6, 2017
• First Posted: November 8, 2017
• Study Start: July 27, 2018
• Primary Completion: December 1, 2018
• Study Completion: June 1, 2019
• Last Updated: November 29, 2018

Record last verified: 2017-11

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)