Early Norepinephrine in Trauma Patients With Hemorrhagic Shock

NCT06977659 | Enrolling By Invitation Phase 1

• 1 other identifier: MURA2025/335
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

Brief Summary

The goal of this clinical trial is to learn if norepinephrine works to treat trauma patients with hemorrhagic shock. It will also learn about the safety of norepinephrine. The main questions it aims to answer are: Does norepinephrine affect the short-term mortality (24-hour mortality)? Does norepinephrine affect the long-term mortality (30-day mortality), survival with favorable outcome, total volume of blood product and crystalloid given in 24 hours, estimated blood loss within 24 hours, resuscitation-related complications, and length of ICU and hospital stay? What medical problems do participants have when receiving norepinephrine? Researchers will compare norepinephrine to a placebo (a look-alike substance that contains no drug) to see if norepinephrine works to treat trauma patients with hemorrhagic shock. Participants will: Receive norepinephrine or a placebo intravenously within 1 hour after randomization, infused for 24 hours after randomization, and then discontinued. Patients are monitored for outcomes and adverse events.

Conditions

Trauma, Multiple

Keywords

Trauma; Norepinephrine; Blood transfusion

Outcome Measures

Primary Outcomes (1)

• 24-hour mortality

  The outcome will be analyzed 24 hours after the patient is enrolled.

  From enrollment to the end of treatment at 24 hour

Secondary Outcomes (3)

• 30-day mortality

  From enrollment to 30 days after treatment.

• Survival with favorable outcome at 30 days

  From enrollment to 30 day after treatment.

• The cumulative volume of blood product within 24 hours

  From enrollment to the end of treatment at 24 hour.

Study Arms (2)

Norepinephrine

ACTIVE COMPARATOR

Norepinephrine bitartrate (LEVOPHEDR, Pfizer inc.) 4 mg/4ml + 5% Dextrose in water 246 ml (total volume 250 ml, final concentration 16 mcg/ml) infuses intravenously via a central catheter or peripheral line with the rate of 10 ml/h (equivalent to 0.05 mcg/kg/min for a 50-kg patient). The drug will be initiated within 1 hour after randomization, infused for 24 hours after randomization, and then discontinued.

Drug: Norepinephrine

Placebo

PLACEBO COMPARATOR

5% Dextrose in water 250 ml infused intravenously at a rate of 10 ml/h. The drug will be initiated within 1 hour after randomization, infused for 24 hours after randomization, and then discontinued.

Drug: Placebo

Interventions

Norepinephrine DRUG

Norepinephrine bitartrate (LEVOPHEDR, Pfizer inc.) 4 mg/4ml + 5% Dextrose in water 246 ml (total volume 250 ml, final concentration 16 mcg/ml) infuses intravenously via a central catheter or peripheral line with the rate of 10 ml/h (equivalent to 0.05 mcg/kg/min for a 50-kg patient). The drug will be initiated within 1 hour after randomization, infused for 24 hours after randomization, and then discontinued.

Norepinephrine

Placebo DRUG

5% Dextrose in water 250 ml infused intravenously at a rate of 10 ml/h. The drug will be initiated within 1 hour after randomization, infused for 24 hours after randomization, and then discontinued.

Placebo

Eligibility Criteria

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

You may qualify if:

• Adult trauma patients aged 18 to 65 years
• Significant bleeding from traumatic events including
• Exsanguinous external bleeding (500 ml or more), or
• Evidence of internal bleeding (e.g., FAST positive, hemothorax, or bleeding seen on CT scan)
• Hemorrhagic shock is defined as:
• Hypotensive event suspected from hemorrhagic shock, characterized by
• Systolic blood pressure less than 90 mmHg,
• Mean arterial pressure less than 65 mmHg, or
• A decrease in blood pressure from baseline more than 30 mmHg (as recorded in the trauma bay, resuscitation room of the emergency department at Ramathibodi Hospital, trauma unit at Siriraj Hospital, or trauma ward/ ICU) OR
• Signs of shock, including:
• Capillary refill time greater than 2 seconds,
• Base excess less than -6 mEq/L,
• Lactate level greater than 2 mmol/L)

You may not qualify if:

• Prehospital cardiopulmonary resuscitation or cardiopulmonary resuscitation at the trauma bay.
• Persistent shock for more than 12 hours prior to randomization.
• Severe traumatic brain injury with Glasgow Coma Scale (GCS) score less than 9 (GCS 3-8)
• Traumatic limb injury with acute limb ischemia
• A history of limb ischemia, chronic heart disease, chronic lung disease, or chronic renal disease
• Pregnant patients
• Documented "Do Not Resuscitate" (DNR) order or who declined life-sustaining intervention before randomization
• Allergic to norepinephrine or contraindications for its use (e.g., peripheral vascular thrombosis, mesenteric thrombosis, and fatal tachyarrhythmia)
• Current use of ergotamine, monoamine oxidase inhibitors (MAOIs), or tricyclic antidepressants (TCAs)
• Prior vasopressor administration before randomization.
• Weight less than 30 kilograms (Extremely low body weight may increases the risk of weight-based dosing issues)

Sponsors & Collaborators

• Visarat Palitnonkiat: lead
• Siriraj Hospital: collaborator

Study Sites (2)

Faculty of Medicine Ramathibodi Hospital

Bangkok, 10400, Thailand

Location

Faculty of Medicine Siriraj Hospital

Bangkok, 10700, Thailand

Location

Related Publications (3)

• Harrois A, Baudry N, Huet O, Kato H, Dupic L, Lohez M, Ziol M, Vicaut E, Duranteau J. Norepinephrine Decreases Fluid Requirements and Blood Loss While Preserving Intestinal Villi Microcirculation during Fluid Resuscitation of Uncontrolled Hemorrhagic Shock in Mice. Anesthesiology. 2015 May;122(5):1093-102. doi: 10.1097/ALN.0000000000000639.

  PMID: 25782753 BACKGROUND

• Cohn SM, DeRosa M, McCarthy J, Song J, White C, Louden C, Ehler B, Michalek J, Landry DW. Characterizing vasopressin and other vasoactive mediators released during resuscitation of trauma patients. J Trauma Acute Care Surg. 2013 Oct;75(4):620-8. doi: 10.1097/TA.0b013e31829eff31.

  PMID: 24064875 BACKGROUND

• Cohn SM, McCarthy J, Stewart RM, Jonas RB, Dent DL, Michalek JE. Impact of low-dose vasopressin on trauma outcome: prospective randomized study. World J Surg. 2011 Feb;35(2):430-9. doi: 10.1007/s00268-010-0875-8.

  PMID: 21161222 BACKGROUND

MeSH Terms

Conditions

Multiple Trauma; Wounds and Injuries

Interventions

Norepinephrine

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 Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: The independent nurse prepares the drug (norepinephrine or placebo) according to the randomization code associated with the study ID and then sends it to the trauma bay. The appearance of both norepinephrine and placebo preparations will be identical. Both patients and physicians will remain blinded after the intervention assignment. An emergency unblinding service is available if the clinician believes that clinical management depends on knowing whether the patient received norepinephrine or placebo. Attending physicians will also be unblinded in the event of serious adverse events that require discontinuation of the study.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Faculty of Medicine Ramathibodi Hospital

Model Details: After the trauma team notifies the nurse about the patient's enrollment, an independent nurse opens an opaque sealed envelope (randomization). Afterward, he or she will prepare the drug (norepinephrine or placebo) according to the assigned group and send it to the trauma bay/ ward. Both norepinephrine preparation and matched placebo will be given intravenously at the rate of 10ml/h.

Study Record Dates

• First Submitted: May 7, 2025
• First Posted: May 18, 2025
• Study Start: May 20, 2025
• Primary Completion (Estimated): July 17, 2027
• Study Completion (Estimated): August 18, 2027
• Last Updated: May 18, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

TH (2)