The purpose of the study is to comparatively evaluate the hemodynamic effects of two treatments when intraoperative hypotension occurs. Patients who require advanced hemodynamic monitoring and develop intraoperative hypotension will be treated with either Cafedrin/Theodrenaline or Noradrenaline after randomisation to one of two study arms. MedDRA version: 20.0 Level: PT Classification code 10062300 Term: Procedural hypotension System Organ Class: 10022117 - Injury, poisoning and procedural co
Conditions
Interventions
Trade Name: Akrinor
Pharmaceutical Form: Solution for injection
INN or Proposed INN: CAFEDRINE HYDROCHLORIDE
CAS Number: 3039-97-2
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type
Sponsors
Ratiopharm GmbH Teva EU Medical Affairs
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: The patient is capable of giving signed informed consent as described in Appendix B which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol; The patient is at least 50 years of age with chronic cardiac failure (NYHA-stages: II-III), is of ASA-Classification: 3 or 4, and has an indication for arterial cannulation and advanced hemodynamic monitoring prior to induction of general anesthesia; The patient is undergoing elective vascular surgery with general anesthesia using Propofol/Fentanyl or Propofol/Sufentanil. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 180 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
Exclusion criteria: The patient has a known hypersensitivity to any components of the IMPs stated in this protocol; The patient has a known hypersensitivity to sodium metabisulfite; The patient has bronchial asthma with sulfite hypersensitivity; The patient has diagnosis of clinical relevant mitral stenosis; The patient has diagnosis of clinical relevant aortic stenosis; The patient has a diagnosis of hyperthyroidism; The patient has a diagnosis of pheochromocytoma; The patient is going to receive any cardiac sensitizing agent (e.g. cyclopropane or halothane) or is going to have deep hypoxia or hypercapnia concomitant to application of IMP; The patient has uncontrolled hypertension as co-morbidity; The patient has sepsis, septic shock, or systemic inflammatory response syndrome (SIRS); The patient is on the following classes of medication that were not withheld on the day of surgery: ACE-Inhibitor /AT2-Antagonists or MAO-Inhibitors. Use of regional anesthesia during study phase 1 and/or study phase 2; The patient is going to receive inhalation anesthesia during study phase 1 and/or 2. The patient cannot exclude pregnancy based on a negative pregnancy test (blood or urine sample) or medical history (menopause, sterilization, amenorrhea).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to compare the hemodynamic effects of the test and reference IMPs administered as bolus injection and subsequent as continuous infusion in a surgical cohort of at-risk adult patients who develop intraoperative hypotension .;Secondary Objective: The secondary effectiveness objectives of the study are to compare hemodynamic measures and study procedures during study phase 1 („bolus phase“, 0-20 Minutes after initial treatment of intraoperative arterial hypotension).;Primary end point(s): (1) Treatment related difference in average MAP [DaMAP] during study phase 2, calculated as the mean difference between areas below the target MAP value (90 mmHg). Non-inferiority is assumed, if DaMAP can be shown to be lower than the non-inferiority margin (5 mmHg) at one-sided alpha-level 0.025. (2) Treatment related difference in average Cardiac Index [DaCI] during study phase 1, calculated as the difference in means of individual areas above the CIref (CIref is individually defined as the CI-measurement at the start of the treatment). Superiority is concluded, if a positive DaCI can be shown at one-sided alpha-level 0.025. ;Timepoint(s) of evaluation of this end point: The duration of the study phase 1 and 2 is two times 20 minutes each. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): (1) Treatment related difference in average MAP [DaMAP] during study phase 1. The estimated DaMAP will be presented along with its two-sided 95% confidence interval. (2) Treatment related differences in: a. change in HR b. change in SVI c. change in SVRI d. change of dP/dtmax e. change in CI f. change in MAP during study phase 1. The estimated treatment related differences will be presented along with their two-sided 95% confidence interval. (3) Ratio of treatment specific incidence rates of overshooting blood pressure (MAP > 110 mmHg) events during study phase 1. The estimated incidence rate ratio will be presented along with its two-sided 95% confidence interval. (4) Ratio of treatment specific incidence rates of low blood pressure (MAP <80 mmHg) events during study phase 1. The estimated incidence rate ratio will be presented along with its two-sided 95% confidence interval. (5) Treatment related differences in number of: a. additional bolus-injections (at MAP <70 mmHg) b. additional measures (volume, position changes etc.) necessary to stabilize blood pressure during study phase 1, where both entities the corresponding contrasts between treatments will be presented along with their two-sided 95% confidence intervals ;Timepoint(s) of evaluation of this end point: The duration of this study phase is 0-20 minutes after initial IMP-Treatment. | — |
Countries
Germany
Contacts
Public ContactDr Susanne Huljic-Lankinen
ratiopharm GmbH
Outcome results
None listed