E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with serious cardiac failure scheduled for non-cardiac surgery |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10006387 |
E.1.2 | Term | Broken hip |
E.1.2 | System Organ Class | 10022117 - Injury, poisoning and procedural complications |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10007559 |
E.1.2 | Term | Cardiac failure congestive |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10007554 |
E.1.2 | Term | Cardiac failure |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10066498 |
E.1.2 | Term | Cardiac failure chronic aggravated |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10007558 |
E.1.2 | Term | Cardiac failure chronic |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10024102 |
E.1.2 | Term | Left cardiac failure |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10007561 |
E.1.2 | Term | Cardiac failure left |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10007555 |
E.1.2 | Term | Cardiac failure (NOS) |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10007564 |
E.1.2 | Term | Cardiac failure, congestive |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10007562 |
E.1.2 | Term | Cardiac failure NOS |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10020100 |
E.1.2 | Term | Hip fracture |
E.1.2 | System Organ Class | 10022117 - Injury, poisoning and procedural complications |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To find differences between the 2 groups on cardiac outcomes. Does levosimendan given prophylactic perioperative, protect or enhance cardiac function compared to placebo?
The primary endpoint is maximum change from baseline to postoperative NT-proBNP value. In addition, mean NT-proBNP response will be estimated over the time for each of the treament groups.
|
|
E.2.2 | Secondary objectives of the trial |
We will also compare infusion with levosimendan vs. placebo for these parameters:
Troponin T, hemodynamic parametres (CI, CO, SV, SVI) cardiovascular complications, use of inotrope/vasopressors, hospital- and ICU-stay, mortality after 30 days. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion Criteria
1. Patients scheduled for acute or elective surgery (there must be time for at least 2 hours of infusion of the study medication prior to the start of surgery)
2. The planned duration of the surgical procedure must be at least one (1) hour
3. The acute surgery has to be either implantation of hemi- or total hip prosthesis
4. The elective surgical procedure must be
Abdominal aortic surgery
Pheripheral surgery on arteries
Carotide surgery (trombenartectomy)
Intraabdominal and intrathoracal surgery
Ortopedic surgery on spine.
Implantation of hemi- or total prothesis - knee or hip.
Radical prostatectomy, transurethral excluded.
Cystectomy
Hysterectomy
Nephrectomy
5. A) Preoperative echovariable test performed within last 12 months prior to inclusion: EF ≤ 35%. If an Acute myocardial infarction (AMI) last 12 months,the echocardiographic test must have been done > 1 months after an AMI or
B) Known cardiac failure.
6. NT-proBNP > 2000 pg/ml or 4000 pg/ml if renal failure (GFR<50)
7. The patient has to use at least one of these medicaments:
a. ACE- inhibitors
b Angiotensin receptor blockers
c. Diuretics
d. Digoxin/Digitoxin
|
|
E.4 | Principal exclusion criteria |
Exclusion Criteria
1. Patients under the age of 18
2. Patients participating in another pharmaceutical study
3. Known abuse of opioids, benzodiazepines, anti-epileptic drugs, α2-agonists or alcohol
4. Pregnant or breastfeeding women. Women of childbearing age must have a negative pregnancy test.
5. Acute myocardial infarction last month before admission
6. Cardiac failure as a result of hypertrophic cardiomyopathy
7. Verified severe aortic stenosis (aortic valve area < 1 cm2) or/and 50 mmHg (mean gradient)
8. Persistent ventricular tachycardia
9. History of torsades des pointes
10. Persistent heart rate > 120/minute
11. Systolic BP < 90 mmHg (non-invasive)
12. S-potassium < 3 mmol/l (treated low s-pottasium to > 3 mmol/l is not an exclusion)
13. Inability to give consent due to, e.g. dementia
14. Hypersensitivity to levosimendan or its excipients
15. Severe liver failure (known liver cirrhosis - Child-Pugh grade C)
16. Severe renal failure (GFR < 30 ml/minute or creatinine > 200 mmol/l). Treated prerenal failure with GFR >30 ml/minute or creatinine < 200 mmol/l is not an exclusion.
17. Prolonged QTc interval (men QTc > 0.43 s, women QTc > 0.45 s)
18. Patient not expected to fullfill the study period according to anesthesiologist estimation
19. Use of sulfonurea medication last 24 hours before inclusion
20. Planned use of ketamine.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
NT-proBNP will be measured preoperatively, thereafter 6, 24, 48, 72, 96, 120, 144, 168 hours after last stitch postoperatively (or only until the patient is discharged from hospital), up to a maximum of 168 hours postoperatively.
The primary endpoint is maximum change from baseline to postoperative NT-proBNP value.
In addition, mean NT-proBNP response will be estimated over the time for each of the treament groups.
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
6, 24, 48, 72, 96, 120, 144, 168 hours after last stitch postoperatively. Blood samples only if attendance at the hospital |
|
E.5.2 | Secondary end point(s) |
Troponin T - myocardial necrosis
Ischemia (ECG)
hemodynamic parametres (CI, CO, SV, SVI)
cardiovascular complications
use of inotrope/vasopressors
hospital- and ICU-stay
mortality after 30 days |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Troponin T - Daily during admission
Ischemia (ECG) - continuous first 24 hours, after that 3rd, 5th and 7th day postoperatively
hemodynamic parametres (CI, CO, SV, SVI) first 24 hours postoperatively
cardiovascular complications - during admission + 30 day follow-up
use of inotrope/vasopressors first 24 hours postoperatively
hospital- and ICU-stay during admission
mortality after 30 days - 30 days follow-up |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 4 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
End of trial is last visit 30 days after surgery. Subsequent if possible follow-up of mortality may optionally be carried out at 6 months and 1 year, using the records system. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |