Clinical trial NCT06885268: The Effect of Noradrenaline Infusion Versus Standard Blood Pressure Management on Perioperative HYPotension in NOn-caRdiac Surgery HYP-NOR Trial
Official title: The Effect of Noradrenaline Infusion Versus Standard Blood Pressure Management on Perioperative HYPotension in NOn-caRdiac Surgery HYP-NOR Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Hypotension
Non-cardiac Surgery
Keywords: perioperative hypotension
non-cardiac surgery
mean arterial pressure
randomized controlled trial
postoperative organ dysfunction
perioperative care
intraoperative hypotension
norepinephrine infusion
noradrenaline infusion
Lead sponsor: Jagiellonian University
Sponsor class: OTHER
Collaborators: name: Medical Research Agency, Poland
First posted: 2025-03-20
Enrollment: 750
Sex: ALL
Minimum age (years): 45
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: Patients will receive either noradrenaline infusion or standard blood pressure management during and up to 4 hours after surgery. Patients and health care providers will not be blinded to patients' allocation to either arm of the trial. Continuous blood pressure measurements will be secured in all patients who do not have an arterial line already in place for other indications using a non-invasive volume-clamp method. The medical team will not be aware of the continuous blood pressure monitoring and will use solely non-invasive blood pressure measurements at time intervals (at least every 5 minutes). In each group, patients will receive balanced crystalloids at 4 ml/kg per hour as maintenance fluid during surgery. In mechanical ventilation, a tidal volume of 8 mL/kg predicted body weight will be recommended. Other ventilatory settings, optimisation of volume status, depth of anaesthesia, patient positioning, as well as prompt diagnosis and treatment of reversible causes of hypotension will be prioritised in all patients in adherence with institutional protocols and current standards of practice.

The study aims to determine whether perioperative noradrenaline infusion can reduce exposure to hypotension compared to reactive treatment of hypotension, whether it is more effective in controlling hypotension during the intraoperatively and postoperatively, whether it reduces the risk of postoperative organ dysfunction, and whether it is safe and does not increase the risk of potential complications.

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

1. 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
2. Persistent difference in recorded SBP between right and left upper limb \>10 mm Hg
3. Persistent atrial fibrillation
4. Have a documented history of dementia
5. Have language, vision, or hearing impairments that may compromise cognitive assessments
6. Have a condition that precludes routine blood pressure management such as surgeon request for relative hypotension
7. Receiving irreversible nonselective monoamine oxidase inhibitors (e.g. tranylcypromine, phenelzine) within 2 weeks preceding study enrolment
8. The use of tricyclic antidepressants
9. Have Prinzmetal angina
10. Have contraindications to noradrenaline per clinician judgement
11. Noradrenaline infusion started before surgery or plan to use continuous noradrenaline infusion throughout the procedure
12. Treating physician (surgeon/anaesthetist) decides on the necessity of extended continuous hemodynamic monitoring during or after surgery
13. Severe kidney disease (MDRD creatinine clearance \<15 mL/min/1.73m2) or renal replacement therapy
14. End-stage heart failure: defined as NYHA Class IV - severe limitations in daily activity. Patients experience symptoms even while at rest. Mostly bedbound patients.
15. 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).
16. Emergency and urgent surgery defined as performed within 24 hours of sudden illness/unplanned admission to hospital
17. Have previously participated in the trial: patient already took a part in the HYP-NOR trial in the past
18. Pregnant or breastfeeding women.

Primary outcomes:
measure: Perioperative hypotension
timeFrame: During and up to 4 hours after surgery
Secondary outcomes:
measure: The duration of hypotension
timeFrame: During and up to 4 hours after surgery
measure: Myocardial Injury after Non-cardiac Surgery (MINS)
timeFrame: During hospitalization and up to 30 days after surgery
measure: Acute kidney injury fulfilling Kidney Disease Improving Global Outcomes (KDIGO) criteria
timeFrame: During hospitalization and up to 30 days after surgery
measure: Stroke
timeFrame: During hospitalization and up to 30 days after surgery
measure: Non-fatal cardiac arrest
timeFrame: During hospitalization and up to 30 days after surgery
measure: Sepsis
timeFrame: During hospitalization and up to 30 days after surgery
measure: Death
timeFrame: During hospitalization and up to 30 days after surgery
measure: Infusion-related reactions
timeFrame: During the infusion of noradrenaline and up to 30 days after drug administration, with assessment occurring postoperatively.
measure: Days alive and out of hospital
timeFrame: 30 days after surgery
measure: Clinically important atrial fibrillation
timeFrame: During hospitalization and up to 30 days after surgery
measure: Major bleeding
timeFrame: During hospitalization and up to 30 days after surgery
measure: Peripheral ischemia
timeFrame: During hospitalization and up to 30 days after surgery
Other outcomes:
measure: Lowest MAP throughout the procedure
timeFrame: During and up to 4 hours after surgery
measure: Lowest MAP for a cumulative case total of 10 minutes
timeFrame: During and up to 4 hours after surgery
measure: Median mean arterial pressure
timeFrame: During and up to 4 hours after surgery
measure: Median heart rate
timeFrame: During and up to 4 hours after surgery
measure: Acute Myocardial Infarction
timeFrame: During hospitalization and up to 30 days after surgery
measure: Peak troponin concentration
timeFrame: The first three days after surgery
measure: Area under the curve troponin
timeFrame: The first three days after surgery
measure: Bradycardia
timeFrame: During surgery, up to 4 hours after surgery, and up to 30 days after surgery.
measure: Acute congestive heart failure
timeFrame: During hospitalization and up to 30 days after surgery
measure: Acute Kidney Injury stage 2-3
timeFrame: 30 days after surgery
measure: Pneumonia
timeFrame: During hospitalization and up to 30 days after surgery
measure: Postoperative pulmonary complications
timeFrame: During hospitalization and up to 30 days after surgery
measure: Surgical site infection
timeFrame: During hospitalization and up to 30 days after surgery
measure: Delirium
timeFrame: First day after surgery
measure: Discharge destination
timeFrame: 30 days after surgery
measure: Cognitive decline
timeFrame: 30 days after surgery
measure: Days alive and outside the intensive care unit
timeFrame: 30 days after surgery
measure: Health-related quality of life
timeFrame: 30 days after surgery
Locations:
city: Katowice
country: Poland
facility: Uniwersyteckie Centrum Kliniczne im. Prof. Kornela Gibińskiego Śląski Uniwersytet Medyczny
city: Kraków
country: Poland
facility: 5 Wojskowy Szpital Kliniczny z Polikliniką Samodzielny Publiczny Zakład Opieki Zdrowotnej w Krakowie
city: Olsztyn
country: Poland
facility: Wojewódzki Szpital Specjalistyczny w Olsztynie
city: Opole
country: Poland
facility: Uniwersytecki Szpital Kliniczny w Opolu
city: Zabrze
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny Nr 1 im. Prof. Stanisława Szyszko Śląskiego Uniwersytetu Medycznego w Katowicach
Study officials:
affiliation: Centre for Intensive Care and Perioperative Medicine, Jagiellonian University Medical College
name: Wojciech Szczeklik, MD, PhD
role: STUDY_DIRECTOR
References: