Early Administration of Norepinephrine in Sepsis

Sepsis, Severe Clinical Trial

— EA-NE-TUN  

Official title:

Early Administration of Norepinephrine in Sepsis (Tunisian Multicenter Randomized Trial)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05836272
• Other study ID #: Tunisian ICUs association
• Status: Recruiting
• Phase: Phase 4
• Start date: August 1, 2023
• Est. completion date: December 2024

Study information

• Verified date: August 2023
• Source: Tunis University
• Contact: Ahlem Trifi
• Phone: 98692699
• Email: trifiahlem2[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

Sepsis is characterized by systemic inflammation induced by a severe infection resulting in an inappropriate host response against that infection. On the microcirculatory scale, vasoplegia with capillary leakage is distinguished. Management of sepsis includes, in addition to specific treatment which includes antimicrobials and eradication of the source, restoration of hemodynamic disorders and assistance to failing organs. In general, the restoration of hemodynamic disorders begins first with volume expansion, followed by the use of vasopressors (mainly norepinephrine: NE as first-line therapy) when the mean arterial pressure target (MAP: reflecting the perfusion pressure organs) is not reached after optimizing the intravascular volume.

Recently, several studies have supported the benefit of administering NE at the start of resuscitation of sepsis. Indeed, its administration at an earlier phase than usually recommended improved MAP and cardiac output with a favorable effect on mortality. At a median interval of 1.3 hours from ICU admission and exclusive administration of NE, MAP was adequately restored within a relatively short time (30 min) and was associated with a better survival rate than that predicted by the severity scores of similar patients from other series reported in the literature. In the recent Thai "CENSER" trial, shock was controlled in 76% of patients in the early NE group versus 48% (p<0.001). On the other hand, the administration of a large quantity of fluids inevitably increases the risk of fluid overload, which is a frequent complication in septic patients. In front of all these arguments, it is therefore tempting to restrict fluid administration even to the initial phase of the hemodynamic management of sepsis by starting NE earlier.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: December 2024
• Est. primary completion date: September 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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,

Related Conditions & MeSH terms

• Sepsis
• Sepsis, Severe
• Toxemia

Intervention

Drug:
• Norepinephrine Bitartrate
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.

Other:
• Placebo
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.

Locations

Country	Name	City	State
Tunisia	intensive care unit of the University Hospital Center La Rabta	Tunis

Sponsors (1)

Lead Sponsor	Collaborator
Tunis University

Country where clinical trial is conducted

Tunisia, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Use of invasive ventilation	Use of invasive ventilation	48 hours
Other	Variation of cardiac output	Variation of Cardiac output assessed xith transthoracic cardiac ultrasound (the 15% threshold is considered to define an increase in CO).	Within 6 hours
Primary	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	Decrease in serum lactate	Decrease in serum lactate > 10% from baseline	within 6 hours
Secondary	Volume of fluid	Quantity of intravenous fluid received	within 48 hours
Secondary	Mortality	Mortality	28 days