Noradrenaline Versus Standard Blood Pressure Management for Perioperative Hypotension in Non-cardiac Surgery

NCT06885268 | Recruiting Phase 3 DMC

• 2 other identifiers: HYP-NOR2023-508255-39-00
• Study Type: interventional
• Target: 750
• Locations: 1 country
• Sites: 5

Brief Summary

The effect of noradrenaline infusion versus standard blood pressure management on perioperative HYPotension in NOn-caRdiac surgery. The study aims to determine whether perioperative noradrenaline infusion is superior to standard blood pressure management for the occurrence of perioperative hypotension.

Conditions

Blood Pressure Management; Intraoperative Hypotension; Non-cardiac Surgery

Keywords

hypotension; noradrenaline infusion; perioperative care

Outcome Measures

Primary Outcomes (1)

• Perioperative hypotension

  Number of episodes of perioperative hypotension defined as any mean arterial pressure (MAP) reading ≤55 mm Hg in the setting of a continuous blood pressure measurement.

  During and up to 4 hours after surgery

Secondary Outcomes (11)

• Myocardial Injury after Non-cardiac Surgery (MINS)

  During hospitalization and up to 30 days after surgery

• Acute kidney injury fulfilling Kidney Disease Improving Global Outcomes (KDIGO) criteria

  During hospitalization and up to 30 days after surgery

• Stroke

  During hospitalization and up to 30 days after surgery

• Non-fatal cardiac arrest

  During hospitalization and up to 30 days after surgery

• Sepsis

  During hospitalization and up to 30 days after surgery

Other Outcomes (19)

• Lowest MAP throughout the procedure

  During surgery

• Median mean arterial pressure

  During and up to 4 hours after surgery

• Median heart rate

  During and up to 4 hours after surgery

Study Arms (2)

Intervention group

ACTIVE COMPARATOR

In the intervention group, a standardized noradrenaline infusion at a concentration of 10 µg/mL will be initiated 15 to 60 seconds before induction of anaesthesia. The infusion will be titrated and maintained during surgery and postoperatively for up to 4 hours, with a minimum duration of 2 hours, until haemodynamic stability is achieved. Haemodynamic stability is defined as stable blood pressure requiring minimal noradrenaline support of 0.01 µg/kg/min or less for at least 1 hour. We will mandate avoidance of mean arterial pressure decreasing below 60 to 70 mm Hg. Once haemodynamic stability is achieved during the postoperative observation period, noradrenaline infusion may be discontinued. Safety criteria for discontinuation include systolic blood pressure above 180 mm Hg, in which case the infusion will be stopped. If systolic blood pressure is between 140 and 170 mm Hg, dose reduction or continuation at a very low noradrenaline infusion of 0.005 µg/kg/min, approximately 1 mL per h

Drug: noradrenaline infusion for management blood pressure

Control group

ACTIVE COMPARATOR

Standard blood pressure management reactive to blood pressure values. According to the 2022 ESA/ESC guidelines, patients in the control group will be treated to avoid a mean arterial pressure below 60 to 70 mm Hg. Ephedrine boluses (5 mg per bolus, up to a total intravenous dose of 25 mg) are recommended as first line treatment for hypotension. If hypotension persists, peripheral noradrenaline may be administered. Due to variability in clinical practice regarding the choice and timing of vasopressors and fluid therapy during and after surgery, further protocolization of hypotension management will not be mandated in order to enhance feasibility and generalizability of the trial.

Combination Product: standard blood pressure management

Interventions

standard blood pressure management COMBINATION_PRODUCT

Patients in the control group will receive standard blood pressure management reactive to blood pressure values. In the light of the current ESA/ESC 2022 guidelines, all patients in the control group will be treated to avoid MAP \<60-70 mm Hg. Ephedrine boluses (5 mg each, up to 25 mg total intravenous dose) will be recommended as a first-line hypotension treatment. Subsequent treatment will involve administering peripheral noradrenaline. Notwithstanding, there is a variation in clinical practice regarding the choice and timing of vasopressors and fluids to be administered during and after surgery, therefore, hypotension treatment will not be further protocolized to increase the feasibility and generalizability of the trial.

Control group

noradrenaline infusion for management blood pressure DRUG

A single concentration of noradrenaline (10 μg/ml) will be initiated 15-60 seconds prior to the induction of anaesthesia, then titrated and maintained until 4 hours after surgery to meet pre-specified mean arterial pressure (MAP) targets. The drug infusion will be started at a dose of 0.01 μg/kg/min and will be titrated to a maximum of 0.1 μg/kg/min. Anaesthesiologists will be advised to use the lowest possible dose of noradrenaline. Avoidance of MAP decreases of \>20% from baseline values or \<60-70 mm Hg will be required in both groups. Individual baseline MAP value will be defined as resting blood pressure obtained in at least two measurements at the surgery ward on the day before surgery. Noradrenaline will be administered peripherally in all patients who do not have a central venous catheter in place.

Intervention group

Eligibility Criteria

• Age: 45 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥45 years old
• Elective or accelerated\* non-cardiac surgery expected to last ≥1 hour and requiring general, neuraxial, or combined general with neuraxial anesthesia
• Expected to stay overnight in the hospital after surgery
• Written informed consent to participate in the HYP-NOR Trial provided
• American Society of Anesthesiologists (ASA) physical status class II or higher.

You may not qualify if:

• Newly diagnosed, untreated, or uncontrolled hypertension -in two measurements on the day before surgery Systolic Blood Pressure (SBP) ≥180 mm Hg or Diastolic Blood Pressure (DBP) ≥110 mm Hg
• Persistent difference in recorded SBP between right and left upper limb \>10 mm Hg
• Persistent atrial fibrillation
• Have a documented history of dementia
• Have language, vision, or hearing impairments that may compromise cognitive assessments
• Have a condition that precludes routine blood pressure management such as surgeon request for relative hypotension
• Receiving irreversible nonselective monoamine oxidase inhibitors (e.g. tranylcypromine, phenelzine) within 2 weeks preceding study enrolment
• The use of tricyclic antidepressants
• Have Prinzmetal angina
• Have contraindications to noradrenaline per clinician judgement
• Noradrenaline infusion started before surgery or plan to use continuous noradrenaline infusion throughout the procedure
• Treating physician (surgeon/anaesthetist) decides on the necessity of extended continuous hemodynamic monitoring during or after surgery
• Severe kidney disease (MDRD creatinine clearance \<15 mL/min/1.73m2) or renal replacement therapy
• End-stage heart failure: defined as NYHA Class IV - severe limitations in daily activity. Patients experience symptoms even while at rest. Mostly bedbound patients.
• Known severe liver disease: defined as the presence of liver cirrhosis or any of the symptoms of severe liver dysfunction: portal hypertension (esophageal varices, ascites), hepatocellular insufficiency (e.g., jaundice, hepatic encephalopathy) and coagulopathy (prolonged INR/APTT associated with known liver dysfunction).

Sponsors & Collaborators

• Jagiellonian University: lead
• Medical Research Agency, Poland: collaborator

Study Sites (5)

Uniwersyteckie Centrum Kliniczne im. Prof. Kornela Gibińskiego Śląski Uniwersytet Medyczny

Katowice, 40-752, Poland

RECRUITING

5 Wojskowy Szpital Kliniczny z Polikliniką Samodzielny Publiczny Zakład Opieki Zdrowotnej w Krakowie

Krakow, 30-901, Poland

RECRUITING

Wojewódzki Szpital Specjalistyczny w Olsztynie

Olsztyn, 10-561, Poland

ACTIVE NOT RECRUITING

Uniwersytecki Szpital Kliniczny w Opolu

Opole, 45-401, Poland

RECRUITING

Samodzielny Publiczny Szpital Kliniczny Nr 1 im. Prof. Stanisława Szyszko Śląskiego Uniwersytetu Medycznego w Katowicach

Zabrze, 41-800, Poland

RECRUITING

MeSH Terms

Conditions

Hypotension

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Study Officials

• Wojciech Szczeklik, MD, PhD

  Centre for Intensive Care and Perioperative Medicine, Jagiellonian University Medical College

  STUDY DIRECTOR

Central Study Contacts

Bożena Seczyńska, PhD

CONTACT

(+48) 124332847; bozena.seczynska@uj.edu.pl

Zbigniew Putowski, MD, PhD

CONTACT

(+48) 126308267; zbigniew.putowski@uj.edu.pl

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medical Sciences, Head of the Department of Intensive Care and Perioperative Medicine Faculty

Study Record Dates

• First Submitted: March 11, 2025
• First Posted: March 20, 2025
• Study Start: June 25, 2025
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2027
• Last Updated: January 14, 2026

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

PL (5)