Clinical trial NCT03021525: Individualized Perioperative Hemodynamic Goal-directed Therapy in Major Abdominal Surgery (iPEGASUS-trial)
Official title: Individualized Perioperative Hemodynamic Goal-directed Therapy in Major Abdominal Surgery (iPEGASUS-trial) - A Multi-center, Prospective, Randomized Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hemodynamic Instability
Cardiac Output, High
Peroperative Complication
Keywords: Goal-directed therapy
postoperative morbidity
haemodynamic optimisation
individualised medicine
Pulse pressure variation
Cardiac output
Lead sponsor: Universitätsklinikum Hamburg-Eppendorf
Sponsor class: OTHER
Collaborators: name: University of Giessen
name: University of Rostock
First posted: 2017-01-16
Enrollment: 380
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: 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.

Detailed description: Postoperative mortality in patients undergoing surgery is on average still 4% in Europe as evaluated recently in a cohort study across 28 European countries and is considered to be even higher in high risk surgery. But besides this significant risk of death, in particular moderate and severe postoperative complications, affecting up to 40% of patients after major surgery, frequently lead to severe reductions of quality of life and cause high healthcare costs in western nations. Perioperative hemodynamic goal-directed optimization is believed to be an integral part to reduce in particular postoperative morbidity significantly and possibly also mortality. Algorithm driven optimization of macrocirculation aiming on best possible oxygen and substrate delivery to end organs and tissues is thought to be the theoretical mechanism of this therapy. A recent large multi-center trial based on such a pragmatic, non-individualized protocol failed to reduce composite morbidity underlining this weak point of this approach. The reason for failing statistically significant improvement of clinical outcome first of all has to be seen in not taking into account individual hemodynamic needs of each single patient. Every patient was hemodynamically treated according to a "one size fits all of maximizing stroke volume" approach. In contrast, a first mono-center trial gave evidence that individualized early goal-directed therapy based on an individually optimized volumetric cardiac preload parameter (global end-diastolic volume) reduces complications and ICU length of stay after cardiac surgery. Further, and even more important, a first multi-center pilot study using a goal-directed algorithm aiming to optimize blood flow oriented on individual cardiac capacities (individualized optimal cardiac index) in major abdominal surgery demonstrated feasibility and a reduction in postoperative complications. This finding needs to be confirmed in a multi-center study that is adequately powered to detect changes in specific complications and in mortality before clinical practice can be changed accordingly. Therefore, the hypothesis of this proposed prospective two arm randomized study is that algorithm driven individualized hemodynamic goal-directed therapy reduces moderate and severe postoperative complications being a massive burden on quality of life and health care costs. The proposed study develops the concept of hemodynamic goal-directed therapy to individually set goals and is designed to assess its impact on morbidity and mortality.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Composite of morbidity and mortality on day 28
timeFrame: 28 days
Secondary outcomes:
measure: Morbidity
timeFrame: Day 1,3,5,7 and 180
measure: Quality of life after 6 months
timeFrame: Time point of enrolment and on day180
measure: Mortality
timeFrame: Day 180
Other outcomes:
Locations:
city: Giessen
country: Germany
facility: Justus-Liebig-University Giessen
city: Hamburg
country: Germany
facility: University Medical Center Hamburg-Eppendorf
city: Rostock
country: Germany
facility: University Medicine Rostock
city: Ferrara
country: Italy
facility: Università degli Studi di Ferrara
city: Genoa
country: Italy
facility: Università degli Studi di Genova
city: Barcelona
country: Spain
facility: Hospital Santa Creu i Sant Pau
city: Valencia
country: Spain
facility: Hospital Universitari i Politécnic La Fe
Study officials:
References:
citation: 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.