Overview
Sponsor-declared trial summary
Phase
Therapeutic confirmatory (Phase III)
Status
Ongoing, recruiting
Participants planned
750
Countries
1
Sites
6
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 in patients having noncardiac surgery.
Key facts
- Sponsor
- Uniwersytet Jagiellonski Collegium Medicum
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Anesthesia and Analgesia [E03], Diseases [C] - Cardiovascular Diseases [C14]
- Trial duration
- 16 Jun 2025 → ongoing
- Decision date (initial)
- 2024-07-22
- Transition trial
- No
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- No
- Funding sources
- Agencja Badań Medycznych
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Therapy, Efficacy
The study aims to determine whether perioperative noradrenaline infusion is superior to standard blood pressure management for the occurrence of perioperative hypotension in patients having noncardiac surgery.
Conditions and MedDRA coding
hypotension in non-cardiac surgery
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 21.0 | LLT | 10056679 | Intraoperative hypotension | 10022117 |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 5
- ≥45years old
- Elective or accelerated* for noncardiac surgery expected to last ≥ 1 hour and requiring general, neuraxial, or combined general & neuraxial anaesthesia
- Expected to require at least overnight hospital stay
- Written informed consent to participate in the HYP-NOR Trial provided
- American Society of Anesthesiologists (ASA) physical status class II or higher.
Exclusion criteria 16
- 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
- End-stage heart failure
- Known severe liver disease
- Emergency and urgent surgery defined as performed within 24 hours of sudden illness/unplanned admission to hospital
- Have previously participated in the trial
- Pregnant or breastfeeding women
- 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
- 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
- Persistent difference in recorded SBP between right and left upper limb >10 mm Hg
- Persistent atrial fibrillation
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- The primary outcome is perioperative hypotension, defined as any mean arterial pressure (MAP) reading ≤55 mmHg during and up to 4 hours after noncardiac surgery.
Secondary endpoints 1
- Secondary outcomes include time under MAP ≤60 mm Hg intraoperatively and postoperatively; a composite of major perfusion-related complications: myocardial injury after noncardiac surgery (MINS), acute kidney injury (AKI), stroke, non-fatal cardiac arrest, sepsis, and death of all causes; infusion-related reactions; days alive and at home up to 30 days after surgery.
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
LEVONOR,1 mg/ml, roztwór do infuzji
PRD325731 · Product
- Active substance
- Norepinephrine
- Substance synonyms
- LEVARTERENOL, Noradrenaline
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- CONCENTRATE FOR SOLUTION FOR INFUSION
- Max daily dose
- 10 µg microgram(s)
- Max total dose
- 10 µg microgram(s)
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- C01CA03 — NOREPINEPHRINE
- Marketing authorisation
- R/3394
- MA holder
- ZAKLADY FARMACEUTYCZNE POLPHARMA S.A.
- MA country
- Poland
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Uniwersytet Jagiellonski Collegium Medicum
- Sponsor organisation
- Uniwersytet Jagiellonski Collegium Medicum
- Address
- Ul. Sw. Anny 12
- City
- Cracow
- Postcode
- 31-008
- Country
- Poland
Scientific contact point
- Organisation
- Uniwersytet Jagiellonski Collegium Medicum
- Contact name
- Wojciech Szczeklik
Public contact point
- Organisation
- Uniwersytet Jagiellonski Collegium Medicum
- Contact name
- Biuro ds. Badań Klinicznych
Locations
1 EU/EEA country · 6 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Poland | Ongoing, recruiting | 750 | 6 |
| Rest of world | — | 0 | — |
Investigational sites
Uniwersyteckie Centrum Kliniczne Im. Prof. K. Gibinskiego Slaskiego Uniwersytetu Medycznego W Katowicach
Klinika Anestezjologii i Intensywnej Terapii, Ul. Ceglana 35, 40-514, Katowice
Uniwersytecki Szpital Kliniczny W Opolu
Klinika Anestezjologii i Intensywnej Terapii, Al. Wincentego Witosa 26, 45-401, Opole
Uniwersytecki Szpital Kliniczny Nr 1 W Lublinie
II Klinika Anestezjologii i Intensywnej Terapii SPSK 1, Ul. Stanislawa Staszica 16, 20-081, Lublin
Samodzielny Publiczny Szpital Kliniczny Nr 1 Im.Prof.Stanislawa Szyszko Slaskiego Uniwersytetu Medycznego W Katowicach
Oddział Anestezjologii i Intensywnej Terapii, Ul. 3 Maja 13/15, 41-800, Zabrze
5 Wojskowy Szpital Kliniczny Z Poliklinika Samodzielny Publiczny Zaklad Opieki Zdrowotnej W Krakowie
Ośrodek Intensywnej Terapii i Medycyny Okołozabiegowej, Ul. Wroclawska 1/3, 30-006, Cracow
Wojewodzki Szpital Specjalistyczny W Olsztynie
Oddział Kliniczny Anestezjologii i Intensywnej Terapii, Ul. Zolnierska 18, 10-561, Olsztyn
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Poland | 2025-06-16 | 2025-06-24 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 9 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol 2023-508255-39 | 2.0 |
| Protocol (for publication) | D1_Protocol 2023-508255-39 approved_blinded | 1.3 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements | 2 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements_leaflet | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF | 3.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF biobank questionaire | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_biobank | 1.1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPc Levonor | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis PL 2023-508255-39 | 1 |
Application history
7 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-03-26 | Poland | Acceptable 2024-07-15
|
2024-07-22 |
| 2 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2025-06-26 | Poland | Acceptable 2024-07-15
|
2025-06-26 |
| 3 | NON SUBSTANTIAL MODIFICATION | NSM-2 | 2025-06-26 | Poland | Acceptable 2024-07-15
|
2025-06-26 |
| 4 | NON SUBSTANTIAL MODIFICATION | NSM-4 | 2025-10-07 | Poland | Acceptable 2024-07-15
|
2025-10-07 |
| 5 | SUBSTANTIAL MODIFICATION | SM-2 | 2025-10-23 | Poland | Acceptable | 2025-12-10 |
| 6 | NON SUBSTANTIAL MODIFICATION | NSM-5 | 2025-12-17 | Poland | Acceptable | 2025-12-17 |
| 7 | NON SUBSTANTIAL MODIFICATION | NSM-6 | 2026-04-28 | Poland | Acceptable | 2026-04-28 |