Evaluating the superiority of VAsopressin versus NOradrenaline in the management of the renal risk patient undergoing cardiac surgery with extracorporeal circulation

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire Dijon Bourgogne

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]

Trial duration

28 Dec 2022 → ongoing

Decision date (initial)

2022-08-01

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2022-500419-38-00

ClinicalTrials.gov

NCT05568160

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To compare 2 blood pressure optimization strategies (vasopressin versus norepinephrine) on the occurrence of a composite end point combining renal complications and death at D7 of the onset of vasoplegic syndrome in patients undergoing cardiac surgery with extracorporeal circulation.

Secondary objectives 12

1. To compare between the two strategies the occurrence of a composite end point combining acute renal failure and death at D30 and D90 of the onset of vasoplegic syndrome
2. To compare between the two strategies mortality within 90 days of the onset of vasoplegic syndrome
3. To compare between the two strategies cardiac complications (including CA/FA) at D7, D30 and D90 of the onset of the vasoplegic syndrome
4. To compare between the two strategies digestive complications at D7, D30 and D90 of the onset of the vasoplegic syndrome
5. To compare between the two strategies cerebral complications (stroke, confusion/disorientation) at D7 of the onset of vasoplegic syndrome
6. To compare between the two strategies the use of rescue norepinephrine after the onset of vasoplegic syndrome
7. To compare between the two strategies the use of inotropic and vasopressor agents from D0 to D7 of the onset of the vasoplegic syndrome
8. To compare between the two strategies Length of stay in the ICU and hospital and associated costs within 90 days of the vasoplegic syndrome
9. To compare between the two strategies the cost-effectiveness ratio at D90, expressed in terms of costs per complication (ARF or death) avoided, from a societal point of view
10. To compare between the two strategies the cost-effectiveness ratio at D90, expressed in terms of costs per life-year gained, from a societal point of view
11. To compare between the two strategies cost-utility ratio at D90, expressed in terms of costs per healthy life-year gained, from a societal perspective
12. To compare between the two strategies complications related to the use of vasopressors at D7 of the onset ofthe vasoplegic syndrome: hyponatremia, hypoperfusion of the extremities, mesenteric ischemia

Conditions and MedDRA coding

vasoplegic syndrome

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Patient who has given free, written and informed consent
2. Patient of legal age
3. Patient requiring cardiac surgery: o Scheduled (> 24h) o With extracorporeal circulation (ECC) o Myocardial revascularization (coronary bypass), and/or surgical correction of valvulopathy (aortic, mitral, pulmonary, tricupsidian), and/or of the ascending aorta and/or removal of an intracardiac tumor, and/or closure of a PFO/ASD
4. Patient with at least 3 risk factors for acute kidney failure including: age > 70 years, combined surgery (more than two procedures), common trunk lesion, preoperative anemia, chronic respiratory failure, obliterative arterial disease of the lower extremities, diabetes, glomerular filtration < 60 ml min-1, LVEF <40%, redux, intra-aortic counterpulsation balloon, expected duration of bypass surgery > 100 min, albuminuria
5. Negative pregnancy test for women of childbearing age

Exclusion criteria 12

1. Patient not affiliated to national health insurance or not beneficiary of a social security system
2. Patient subject to a measure of legal protection (curatorship, guardianship)
3. Pregnant, parturient or breastfeeding women
4. Patients of legal age who are incapable or unable to express their consent
5. Patients who have already been included in this study
6. Patients requiring emergency surgery (less than 24 hours)
7. Patient with chronic kidney failure on dialysis
8. Patient with a cardiac transplant
9. Patient on left-sided monoventricular assistance
10. Patient on ECMO/ECLS
11. Patient with acute circulatory failure in the immediate preoperative period (sepsis, hemorrhage)
12. Patients with known hypersensitivity to the active ingredient (argipressin) or to one of the excipients of REVERPLEG®

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Occurrence of a renal complication or death from the onset of vasoplegic syndrome until 7 days after. Renal complications are defined as the occurrence of acute kidney failure as defined by the KDIGO definition (stage 1 or higher), and/or the initiation of renal replacement therapy

Secondary endpoints 14

1. The occurrence of a renal complication (as defined in the primary endpoint) or death within 90 days of the onset of vasoplegic syndrome
2. Mortality within 90 days of the onset of vasoplegic syndrome
3. Occurrence of a cardiac complication as listed below at 7, 30, and 90 days after the onset of vasoplegic syndrome: arrhythmia requiring treatment , postoperative myocardial damage, myocardial infarction defined by an increase in cardiac enzymes plus the appearance of a new Q wave, and/or an abnormality of kinetics on echocardiography, cardiorespiratory arrest
4. The occurrence of a digestive complication as listed below at 7, 30 and 90 days after the onset of the vasoplegic syndrome: mesenteric ischemia, ischemic colitis diagnosed by an imaging examination (CT scan, endoscopy) or the need for a reoperation for digestive complication in the aftermath of the cardiac surgery
5. The occurrence of a cerebral complication as listed below within 7 days of the onset of the vasoplegic syndrome: stroke, delirium (identified by the CAM-ICU test)
6. The number of patients requiring rescue norepinephrine after the onset of vasoplegic syndrome in the OR and postoperatively
7. The total dose (mg) of norepinephrine for patients requiring rescue norepinephrine after the onset of vasoplegic syndrome in the OR and postoperatively
8. The Vasoactive Inotropic Score at D0, D1, D2, D7 of the onset of the vasoplegic syndrome (VIS = dopamine dose (mcg kg-1 min-1) + dobutamine dose (mcg kg-1 min-1) + 100 x adrenaline dose (mcg kg-1 min- 1) + 10 x dose of milrinone (mcg kg-1 min-1) + 10,000 x dose of vasopressin (units/kg/min) + 100 x dose of norepinephrine (mcg kg-1 min-1) + 10 x dose of phenylephrine (mcg kg-1 min-1)
9. The length of stay in the ICU and hospital (number of days) at D90 of the onset of the vasoplegic syndrome
10. The difference in mean costs of ICU and hospital stays at D90 of vasoplegic syndrome onset
11. The incremental cost-effectiveness ratio at D90 of onset of vasoplegic syndrome, expressed as the cost per additional complication avoided by the vasopressin strategy compared with the noradrenaline strategy
12. The incremental cost-effectiveness ratio at D90 of the onset of vasoplegic syndrome, expressed as the cost per additional year of life gained with the vasopressin strategy compared with the noradrenaline strategy
13. Incremental cost-effectiveness ratio at D90 of the onset of vasoplegic syndrome, expressed in terms of cost per additional healthy life-year gained (cost/QALY) with the vasopressin strategy compared with the noradrenaline strategy
14. The occurrence of hyponatremia (Na+ <130 mmol l-1), hypoperfusion of the extremities (cyanosis/necrosis of the extremities) at D7

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire Dijon Bourgogne

Sponsor organisation

Centre Hospitalier Universitaire Dijon Bourgogne

Address

1 Boulevard Jeanne D Arc

City

Dijon

Postcode

21000

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire Dijon Bourgogne

Contact name

Chef de projets recherche

Public contact point

Organisation

Centre Hospitalier Universitaire Dijon Bourgogne

Contact name

Chef de projets recherche

Locations

1 EU/EEA country · 6 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Application history

2 submissions — initial application plus substantial / non-substantial modifications