Noradrenaline versus usual blood pressure care during non-cardiac surgery

The Effect of Noradrenaline Infusion Versus Standard Blood Pressure Management on Perioperative HYPotension in NOn-caRdiac Surgery HYP-NOR Trial

This test tries a continuous noradrenaline infusion during and for four hours after non-cardiac surgery to see if it reduces episodes of low blood pressure in adults aged 45 and older compared with usual blood pressure care.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 750 (estimated)
• Ages: 45 Years and up
• Sex: All
• Sponsor: Jagiellonian University (other)
• Locations: 5 sites (Katowice and 4 other locations)
• Trial ID: NCT06885268 on ClinicalTrials.gov

What this trial studies

Adults having elective or accelerated non-cardiac surgery expected to last at least one hour are randomized to receive either a continuous perioperative noradrenaline infusion (continued up to four hours after surgery) or standard reactive blood pressure management. The trial is open-label to clinicians, while continuous non-invasive blood pressure is recorded covertly using a volume-clamp method and routine intermittent measurements guide care. All participants receive standardized intraoperative care including balanced crystalloids at 4 ml/kg/hour and recommended tidal volumes of 8 ml/kg predicted body weight, with attention to volume status, depth of anaesthesia, positioning, and prompt treatment of reversible causes of hypotension. The primary aim is to see whether proactive noradrenaline reduces the duration and severity of perioperative hypotension compared with reactive treatment.

Who should consider this trial

Good fit: Adults aged 45 or older scheduled for elective or accelerated non-cardiac surgery lasting at least one hour who require general or neuraxial anaesthesia, expect an overnight hospital stay, and are ASA class II or higher.

Not a fit: Patients with uncontrolled or very high blood pressure, persistent atrial fibrillation, documented dementia, significant sensory or language impairments, surgeon-requested permissive hypotension, or other protocol exclusions are unlikely to be eligible or to benefit.

Why it matters

Potential benefit: If successful, proactive noradrenaline could reduce the time patients spend with low blood pressure around surgery and may lower complications associated with perioperative hypotension.

How similar studies have performed: Prior smaller perioperative studies of prophylactic vasopressors (including noradrenaline and phenylephrine) have reduced episodes of intraoperative hypotension, but large trials showing clear reductions in downstream clinical complications remain limited.

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.

Where this trial is running

Katowice and 4 other locations

• Uniwersyteckie Centrum Kliniczne im. Prof. Kornela Gibińskiego Śląski Uniwersytet Medyczny — Katowice, Poland (RECRUITING)
• 5 Wojskowy Szpital Kliniczny z Polikliniką Samodzielny Publiczny Zakład Opieki Zdrowotnej w Krakowie — Krakow, Poland (RECRUITING)
• Wojewódzki Szpital Specjalistyczny w Olsztynie — Olsztyn, Poland (ACTIVE_NOT_RECRUITING)
• Uniwersytecki Szpital Kliniczny w Opolu — Opole, Poland (RECRUITING)
• Samodzielny Publiczny Szpital Kliniczny Nr 1 im. Prof. Stanisława Szyszko Śląskiego Uniwersytetu Medycznego w Katowicach — Zabrze, Poland (RECRUITING)

Study contacts

• Study coordinator: Bożena Seczyńska, PhD

Conditions: Blood Pressure Management, Intraoperative Hypotension, Non-cardiac Surgery, hypotension, noradrenaline infusion, perioperative care