Early Administration of Norepinephrine in Sepsis

NCT05836272 | Recruiting Phase 4

• 1 other identifier: Tunisian ICUs association
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

The management of septic states includes, in addition to the specific treatment (antimicrobials and eradication of the source), a restoration of the hemodynamic disorders and assistance of the failing organs. In general, the restoration of hemodynamic disorders begins first with volume expansion, followed by the use of Noepinephrine (NE) when the target mean arterial pressure (MAP) is not reached after optimizing the intravascular volume. Recently, several studies have supported the interest of early NE on MAP, cardiac output and mortality. It is therefore tempting to restrict fluid administration even in the initial phase of hemodynamic management of severe sepsis by starting NE earlier.

Conditions

Sepsis, Severe

Keywords

sepsis; septic shock; Norepinephrine; volume expansion; mortality

Outcome Measures

Primary Outcomes (1)

• shock control

  shock control is defined by a composite criterion (MAP \> 65 mm Hg for 2 consecutive measurements and urinary output \> 0.5 ml/kg/h for 2 consecutive hours)

  within 6 hours

Secondary Outcomes (3)

• Decrease in serum lactate

  within 6 hours

• Volume of fluid

  within 48 hours

• Mortality

  28 days

Other Outcomes (2)

• Use of invasive ventilation

  48 hours

• Variation of cardiac output

  Within 6 hours

Study Arms (2)

Early NE

ACTIVE COMPARATOR

The early NE arm will receive low-dose NE as soon as hypotension secondary to sepsis is observed in addition to a classic therapeutic regimen that complies with the guidelines of the 2021 Surviving Sepsis Compaign. Sepsis is defined according to the sepsis 3 consensus by a sepsis related organ failure assessment (SrOFA) score greater than 2 following an infection (documented or suspected)

Drug: Norepinephrine Bitartrate

Placebo

PLACEBO COMPARATOR

The placebo arm will receive only the classic therapeutic regimen that complies with the guidelines of the 2021 Surviving Sepsis Compaign.

Other: Placebo

Interventions

Norepinephrine Bitartrate DRUG

The NE will be prepared as follows: 4 mg mixed with 250 ml of 5% glucose resulting in a final norepinephrine concentration of 0.016 mg/ml. For the control group placebo: 250 ml of 5% glucose will be prepared. Both drugs will be infused via a peripheral line or a venous catheter. The intravenous infusion rate varies from 8 to 15 ml/hour, adjusted according to body weight to obtain norepinephrine at 0.05 microgram/kg/min (ie 0.128 to 0.24 mg per hour) in continuous infusion.

Also known as: Norepinephrine 0,016 mg/ml

Early NE

Placebo OTHER

For the control group placebo: 250 ml of 5% glucose will be prepared and will be infused via a peripheral line or a venous catheter. The intravenous infusion rate varies from 8 to 15 ml/hour.

Placebo

Eligibility Criteria

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

You may qualify if:

• Age 18 or older.
• The patient or his/her legal representative has given informed consent in writing.
• Diagnosis of sepsis according to the definitions updated by the consensus of sepsis 3.
• Mean arterial pressure \< 65 mmHg

You may not qualify if:

• Diagnosis of septic shock prior to randomization (where NA requirements exceed those of the trial protocol)
• Pregnancy,
• Need for immediate surgery,
• Neoplasia at an advanced stage
• Circumstances where water restriction is the rule:
• Acute pulmonary edema
• Acute coronary syndrome,

Sponsors & Collaborators

• Tunis University: lead

Study Sites (1)

intensive care unit of the University Hospital Center La Rabta

Tunis, 1007, Tunisia

RECRUITING

Related Publications (2)

• Permpikul C, Tongyoo S, Viarasilpa T, Trainarongsakul T, Chakorn T, Udompanturak S. Early Use of Norepinephrine in Septic Shock Resuscitation (CENSER). A Randomized Trial. Am J Respir Crit Care Med. 2019 May 1;199(9):1097-1105. doi: 10.1164/rccm.201806-1034OC.

  PMID: 30704260 BACKGROUND

• Trifi A, Abdellatif S, Mehdi A, Messaoud L, Seghir E, Mrad N, Ben Khelil J, Ben Ismail K, Merhaben T, Fradj H, Mokline A, Messaadi AA, Khiari H, Garbaa Y, Borsali Falfoul N, Ennouri E, Toumi R, Boussarsar M, Jaoued O, Atrous S, Ghezala HB, Brahmi N, Trabelsi I, Ghadhoune H, Bradaii S, Bahloul M, Ammar R, Kaaniche FM. Early administration of norepinephrine in sepsis: Multicenter randomized clinical trial (EA-NE-S-TUN) study protocol. PLoS One. 2024 Jul 18;19(7):e0307407. doi: 10.1371/journal.pone.0307407. eCollection 2024.

  PMID: 39024364 DERIVED

MeSH Terms

Conditions

Sepsis; Shock, Septic

Interventions

Norepinephrine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Biogenic Monoamines; Biogenic Amines; Catecholamines; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

• Ahlem Trifi

  Hopital La Rabta

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ahlem Trifi

CONTACT

98692699; trifiahlem2@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: This involves randomizing 2 independent groups according to a succession of six blocks of random permutations and this will be carried out using a computer-generated tool: the NE group (early noradrenaline group) which will receive NA at start for correction of hypotension and Placebo group (standard treatment group).

Study Record Dates

• First Submitted: April 18, 2023
• First Posted: May 1, 2023
• Study Start: August 1, 2023
• Primary Completion: June 1, 2025
• Study Completion: August 1, 2025
• Last Updated: December 4, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

TU (1)