Clinical trial NCT05648279: Personalized Hemodynamic Management in High-risk Major Abdominal Surgery
Official title: Personalized Hemodynamic Management Targeting Preoperative Baseline Cardiac Index in High-risk Patients Having Major Abdominal Surgery: the International Multicenter Randomized PELICAN Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Cardiac Output
Surgery
Postoperative Complications
Anesthesia
Lead sponsor: Universitätsklinikum Hamburg-Eppendorf
Sponsor class: OTHER
First posted: 2022-12-13
Enrollment: 1128
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Postoperative mortality within 30 days after surgery is around 2% in patients having major noncardiac surgery in Europe and the USA. In fact, if the first 30 days after surgery were considered a disease, it would be the third leading cause of death globally. Postoperative deaths are a consequence of postoperative organ injury and complications - including acute myocardial injury, acute kidney injury, and severe infectious complications. To avoid postoperative deaths, it is thus crucial to reduce postoperative organ injury and complications. To reduce postoperative organ injury and complications, modifiable risk factors need to be addressed. These modifiable risk factors for postoperative organ injury include low blood flow states and intraoperative hypotension. Optimizing blood flow (i.e., cardiac index) during surgery may thus be effective in reducing postoperative organ injury and complications. However, the optimal hemodynamic treatment strategy for high-risk surgical patients remains unclear. Cardiac index varies substantially between individuals. However, current intraoperative hemodynamic treatment strategies mainly aim to maximize cardiac index instead of using personalized cardiac index targets for each individual patient. A single-center pilot trial suggests that using individualized cardiac index targets during surgery may reduce postoperative organ injury and complications compared to routine hemodynamic management. However, large robust trials investigating the effect of personalized hemodynamic management targeting preoperative baseline cardiac index on postoperative complications are missing.

The investigators, therefore, propose a multicenter randomized trial to test the hypothesis that personalized hemodynamic management targeting preoperative baseline cardiac index reduces the incidence of a composite outcome of acute kidney injury, acute myocardial injury, non-fatal cardiac arrest, severe infectious complications, and death within 7 days after surgery compared to routine hemodynamic management in high-risk patients having major abdominal surgery.

Detailed description: not provided

Eligibility criteria: Inclusion Criteria:

Consenting patients ≥45 years scheduled for elective major abdominal surgery (involving visceral organs) under general anesthesia that is expected to last ≥90 minutes AND presence of ≥1 of the following high-risk criteria:

* exercise tolerance \<4 metabolic equivalents as defined by the guidelines of the American College of Cardiology/American Heart Association
* renal impairment (serum creatinine ≥1.3 mg dL-1 or estimated glomerular filtration rate \<90 mL min-1 (1.73 m2)-1 within the last 6 months
* coronary artery disease
* chronic heart failure (New York Heart Association Functional Classification ≥II)
* valvular heart disease (moderate or severe)
* history of stroke
* peripheral arterial occlusive disease (any stage)
* chronic obstructive pulmonary disease (any stage) or pulmonary fibrosis (any stage)
* diabetes mellitus requiring oral hypoglycemic agent or insulin
* immunodeficiency due to a disease (e.g., HIV, leukemia, multiple myeloma) or therapy (e.g., immunosuppressants, chemotherapy, radiation, steroids \[above Cushing threshold\])
* liver cirrhosis (any Child-Pugh class)
* body mass index ≥30 kg m-2
* history of smoking within two years of surgery
* age ≥65 years
* expected surgery duration ≥180 minutes
* B-type natriuretic peptide (BNP) \>80 ng/L or N-terminal B-type natriuretic peptide (NT-proBNP) \>200 ng/L within the last 6 months

Exclusion Criteria:

* emergency surgery
* ambulatory surgery
* planned surgery: nephrectomy, liver or kidney transplantation surgery
* status post transplantation of kidney, liver, heart, or lung
* sepsis (according to current Sepsis-3 definition)
* American Society of Anesthesiologists physical status classification V or VI
* pregnancy
* impossibility of preoperative baseline cardiac index assessment using bioreactance
* impossibility to perform cardiac index monitoring using the Starling Fluid Management System (Baxter, Deerfield, IL, USA)
* current participation in another clinical trial or treatment with a similar biological mechanism or primary outcome measure

Primary outcomes:
measure: Composite outcome of major postoperative complications
timeFrame: Postoperative Day 7
Secondary outcomes:
measure: Composite outcome of major postoperative complications
timeFrame: Postoperative Day 3
measure: Postoperative acute kidney injury
timeFrame: Postoperative Day 3
measure: Postoperative acute kidney injury
timeFrame: Postoperative Day 7
measure: Postoperative acute myocardial injury
timeFrame: Postoperative Day 3
measure: Postoperative acute myocardial injury
timeFrame: Postoperative Day 7
measure: Postoperative severe infectious complications
timeFrame: Postoperative Day 3
measure: Postoperative severe infectious complications
timeFrame: Postoperative Day 7
measure: Postoperative non-fatal cardiac arrest
timeFrame: Postoperative Day 3
measure: Postoperative non-fatal cardiac arrest
timeFrame: Postoperative Day 7
measure: Postoperative death
timeFrame: Postoperative Day 3
measure: Postoperative death
timeFrame: Postoperative Day 7
measure: Composite outcome of long-term postoperative complications
timeFrame: Postoperative Day 30
measure: Composite outcome of long-term postoperative complications
timeFrame: Postoperative Day 90
measure: Postoperative need for renal replacement therapy
timeFrame: Postoperative Day 30
measure: Postoperative need for renal replacement therapy
timeFrame: Postoperative Day 90
measure: Postoperative myocardial infarction
timeFrame: Postoperative Day 30
measure: Postoperative myocardial infarction
timeFrame: Postoperative Day 90
measure: Postoperative non-fatal cardiac arrest
timeFrame: Postoperative Day 30
measure: Postoperative non-fatal cardiac arrest
timeFrame: Postoperative Day 90
measure: Postoperative death
timeFrame: Postoperative Day 30
measure: Postoperative death
timeFrame: Postoperative Day 90
measure: Postoperative fever
timeFrame: Postoperative Day 7
measure: Postoperative respiratory infection
timeFrame: Postoperative Day 7
measure: Postoperative neurological infection
timeFrame: Postoperative Day 7
measure: Postoperative urinary system infection
timeFrame: Postoperative Day 7
measure: Postoperative colitis or infection with Clostridium difficile
timeFrame: Postoperative Day 7
measure: Postoperative endometritis
timeFrame: Postoperative Day 7
measure: Postoperative deep incisional surgical site infection
timeFrame: Postoperative Day 7
measure: Postoperative organ or space surgical site infection
timeFrame: Postoperative Day 7
measure: Postoperative unknown infection with pathogenic organisms in tissue or fluid
timeFrame: Postoperative Day 7
measure: Postoperative sepsis
timeFrame: Postoperative Day 7
measure: Transfer from intensive care unit to normal ward
timeFrame: Postoperative Day 90
measure: Hospital discharge
timeFrame: Postoperative Day 90
measure: Unplanned hospital re-admission
timeFrame: Postoperative Day 30
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Hvidovre Hospital
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Copenhagen
country: Denmark
facility: University Medical Center Copenhagen Bispebjerg and Frederiksberg
city: Düsseldorf
country: Germany
facility: University Hospital Düsseldorf
city: Hamburg
country: Germany
facility: University Medical Center Hamburg
city: Lübeck
country: Germany
facility: University Medical Center Schleswig Holstein, Lübeck
city: Marburg
country: Germany
facility: University Hospital Marburg
city: Munich
country: Germany
facility: LMU Munich
city: Pamplona
country: Spain
facility: Clínica Universidad de Navarra
Study officials:
affiliation: Universitätsklinikum Hamburg-Eppendorf
name: Bernd Saugel, M.D.
role: PRINCIPAL_INVESTIGATOR
References: