Individualized Perioperative Hemodynamic Goal-directed Therapy in Major Abdominal Surgery (iPEGASUS-trial)

NCT03021525 | Completed

• 1 other identifier: 301116
• Study Type: interventional
• Target: 380
• Locations: 3 countries
• Sites: 7

Brief Summary

To evaluate the impact of perioperative, algorithm driven, hemodynamic therapy based on individualized fluid and cardiac output optimization on postoperative moderate and severe complications in patients undergoing major abdominal surgery including visceral, urological, and gynecological operations. In the proposed study, hemodynamic therapy is tailored individually to each patient, based on individual preload optimization by the functional parameter "pulse pressure variation (PPV)" and based on an individually titrated goal of cardiac index. The proposed study therefore further develops the concept of hemodynamic goal-directed therapy to individually set goals and is designed to assess its impact on morbidity and mortality.

Conditions

Hemodynamic Instability; Cardiac Output, High; Peroperative Complication

Keywords

Goal-directed therapy; postoperative morbidity; haemodynamic optimisation; individualised medicine; Pulse pressure variation; Cardiac output

Outcome Measures

Primary Outcomes (1)

• Composite of morbidity and mortality on day 28

  Considering the high relevance for the individual patient and the society, postoperative outcome is most appropriately reflected by a combination of morbidity and mortality. Therefore, the primary endpoint is a composite comprising rate of patients with one or more moderate or severe postoperative complications or death within 28 days post surgery. Moderate and severe postoperative complications are defined on the basis of a consensus statement of an ESA (European Society of Anesthesiology)- ESICM (European Society of Intensive Care Medicine) joint task force on perioperative outcome measures.

  28 days

Secondary Outcomes (3)

• Morbidity

  Day 1,3,5,7 and 180

• Quality of life after 6 months

  Time point of enrolment and on day180

• Mortality

  Day 180

Study Arms (2)

Individualized Goal Directed Therapy (iGDT)

EXPERIMENTAL

Patients receive fluids and catecholamines following a protocol of individualized parameters achieved by extended hemodynamic monitoring.

Procedure: Individualized Goal Directed Therapy

Control

ACTIVE COMPARATOR

Patients in the control group will be treated according to established basic treatment goals.

Procedure: Control Group

Interventions

Individualized Goal Directed Therapy PROCEDURE

The trial intervention period will commence from the induction of anesthesia until 8 hours after surgery, or until discharging from the postoperative intensive or intermediate care unit. All patients in the intervention group receive basic vital sign monitoring. For inotropic support dobutamine, and as vasopressor norepinephrine are drugs of choice. Hemodynamic management is performed according to standard treatment until an arterial line is placed. The signal of the arterial line is then processed either by calibrated or non-calibrated pulse contour analysis for pulse pressure variation (PPV) and cardiac index (CI) measurement. Fluid challenge will be performed by infusion of 500 ml in \<15 minute. Choice of fluid in case of indicated fluid loading is determined on basis of the recent guideline for intravasal volume therapy. Patients receive fluids and vasoactive agents following a protocol of individualized parameters regularly achieved by extended hemodynamic monitoring.

Individualized Goal Directed Therapy (iGDT)

Control Group PROCEDURE

Patients in the control group will be treated according to established basic treatment goals (heart rate \<100 bpm, mean arterial pressure \>65 mmHg, SpO2\>94%, and core temperature \>36° C). Basic anesthesiological monitoring by five-lead-electrocardiogram, pulse oximetry, non-invasive blood pressure monitoring and capnography is performed in every patient of the control group. Placement of an arterial and central venous line, as well as fluid and catecholamines administration, are at the discretion of the treating clinician.

Control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• To provide high generalizability and representativeness the high number of patients with laparotomy and major surgical trauma is included into this study. - Therefore, open visceral, urological, and gynecological surgery is covered by this study.
• Expected duration of surgery must be ≥ 120 minutes and requirement of volume therapy needs to be expected ≥ 2 liters.
• Risk for any postoperative complications needs to be ≥10% assessed by the ACS (American College of Surgery)- NSQUIP (National Surgical Quality Improvement Program) risk calculator.

You may not qualify if:

• Patients \<18 years,
• laparoscopic approach,
• patients not having sinus rhythm,
• patients having highly impaired left ventricular function (ejection fraction \<30%) or severe aortic valve stenosis (aortic valve area \<1 cm2, mean gradient \>40 mmHg),
• pregnant women,
• emergency surgeries (surgery required within 24 hours),
• primarily vascular surgery,
• patients suffering from septic shock,
• patients having phaeochromocytoma,
• patients suffering from non-cardiac chest pain,
• refusal of consent,
• patients receiving palliative treatment only (likely to die within 6 months) and patients suffering from acute myocardial ischemia (within 30 days before randomization) are excluded from the study.
• Further, in case that clinicians intended to use cardiac output monitoring for clinical reasons patients should also not be included in the study.

Sponsors & Collaborators

• Universitätsklinikum Hamburg-Eppendorf: lead
• University of Giessen: collaborator
• University of Rostock: collaborator

Study Sites (7)

Justus-Liebig-University Giessen

Giessen, Germany

Location

University Medical Center Hamburg-Eppendorf

Hamburg, 20246, Germany

Location

University Medicine Rostock

Rostock, Germany

Location

Università degli Studi di Ferrara

Ferrara, Italy

Location

Università degli Studi di Genova

Genoa, Italy

Location

Hospital Santa Creu i Sant Pau

Barcelona, Spain

Location

Hospital Universitari i Politécnic La Fe

Valencia, Spain

Location

Related Publications (2)

• Funcke S, Schmidt G, Bergholz A, Argente Navarro P, Azparren Cabezon G, Barbero-Espinosa S, Diaz-Cambronero O, Edinger F, Garcia-Gregorio N, Habicher M, Klinkmann G, Koch C, Kroker A, Mencke T, Moral Garcia V, Zitzmann A, Lezius S, Pepic A, Sessler DI, Sander M, Haas SA, Reuter DA, Saugel B. Cardiac index-guided therapy to maintain optimised postinduction cardiac index in high-risk patients having major open abdominal surgery: the multicentre randomised iPEGASUS trial. Br J Anaesth. 2024 Aug;133(2):277-287. doi: 10.1016/j.bja.2024.03.040. Epub 2024 May 26.

  PMID: 38797635 DERIVED

• Funcke S, Saugel B, Koch C, Schulte D, Zajonz T, Sander M, Gratarola A, Ball L, Pelosi P, Spadaro S, Ragazzi R, Volta CA, Mencke T, Zitzmann A, Neukirch B, Azparren G, Gine M, Moral V, Pinnschmidt HO, Diaz-Cambronero O, Estelles MJA, Velez ME, Montanes MV, Belda J, Soro M, Puig J, Reuter DA, Haas SA. Individualized, perioperative, hemodynamic goal-directed therapy in major abdominal surgery (iPEGASUS trial): study protocol for a randomized controlled trial. Trials. 2018 May 9;19(1):273. doi: 10.1186/s13063-018-2620-9.

  PMID: 29743101 DERIVED

MeSH Terms

Conditions

Cardiac Output, High; Intraoperative Complications

Interventions

Control Groups

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Pathologic Processes

Intervention Hierarchy (Ancestors)

Epidemiologic Research Design; Epidemiologic Methods; Investigative Techniques; Research Design; Methods

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 12, 2017
• First Posted: January 16, 2017
• Study Start: August 29, 2017
• Primary Completion: March 27, 2023
• Study Completion: August 26, 2023
• Last Updated: January 17, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

IT (2); ES (2); DE (3)