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Effectiveness of the Use of the New Hemostatic Patch Hemopatch ® in Patients Undergoing Surgical Liver Resection

Phase 3
Conditions
Liver Damage
Surgery
Interventions
Other: Control
Device: Hemopatch
Registration Number
NCT02769754
Lead Sponsor
Instituto de Investigacion Sanitaria La Fe
Brief Summary

This prospective randomized study aims to determine the influence of the use of local hemostatic on the incidence of local complications derived from the edge of transection: biliary fistula or bleeding, after scheduled hepatic resection.

Detailed Description

Achieving adequate hemostasis is a fundamental prerequisite to successfully perform any surgical procedure, but particularly in cases of visceral abdominal surgery, where a slight bleeding, apparently insignificant, can end in significant bleeding (Haas et al Clinic and Applied thombosis 2006).

Control of intraoperative bleeding is initially performed using traditional techniques such as compression, ligatures, clips, Electrocautery, or clamps. The traditional surgical techniques often fail to prevent bleeding, despite performing a careful and meticulous hemostasis.

The morbidity after elective liver surgery has been reduced in hepatobiliary surgery centers mainly after standardizing anatomical liver resections. These techniques decrease necrosis, bleeding, and the incidence of biliary fistulas (Kraus et al J Am Coll Surg 2005).

Bleeding and biliary fistula are the main determinants of postoperative liver morbidity, with an incidence around 4.2-10% and 4-17% respectively (Yamashita et al Ann Surg 2001; Jin et al World J Gastroenterology 2013).

This complication is difficult to handle especially in patients with cirrhosis or liver cancer, because of reduced platelet and blood coagulation activity (Figueras et al Ann Surg 2007).

Moreover, it is particularly difficult to determine the individual risk of rebleeding or biliary fistula during the intraoperative time.

Many adjuvant surgical hemostatic procedures have been tested in the liver: such as oxidized cellulose, absorbable sponges, fibrillar collagen, and fibrin sealants.

There is an extensive published literature reporting the use of adhesives, Sealants, and topical hemostatics in surgery. There is little doubt that the hemostatic effects of these devices produce a beneficial impact on blood loss. However, there is a wide variation in the literature results. Most of the initial clinical data were obtained in cardiovascular surgery. The only trial that has provided the most significant data in hemostatic efficacy was published by Rousou et al in J Thorac Cardiol South 1999. In this randomized multicenter study, 333 patients that underwent emergency cardiac reoperations were randomized to receive either conventional treatment with fibrinogen or other hemostatic. The 92% of the patients assigned to receive fibrin sealant had a complete hemostasis at 5 minutes, compared with the 12% of those treated with other topical hemostatic.

In clinical practice is difficult to quantify the efficacy of the topical hemostatics on hemostasis. The overall effect of perioperative blood loss can only be inferred indirectly by volume drainage and the number of transfused concentrates (Kraus et al J Am Coll Surg 2005).

The volume of blood loss during liver surgery depends on many factors: systemic coagulation, underlying disease, surgery complexity, surgeon experience, central venous pressure, and local hemodynamics.

Moreover, bile leakages are much harder to identify, define, and particularly to quantify, when compared to bleeding. The biliary system is a low pressure system (less than venous pressure). Animal studies have shown that the use of collagen adhesives is effective for preventing biliary fistulas (Wise et al Am Surg 2002).

In a cohort study of 32 adult patients, in which a right hepatic lobe Split was held, it was compared the use of Tachosil ® versus fibrin glue. The transection area was treated with fibrin glue in 16 patients and with Tachosil ® in the other 16 ones. No differences were observed regarding the need of postoperative transfusion. Nevertheless, the group of patients treated with the fibrin patch showed a significantly lower incidence of bile leakage. Those findings were justified based on the assumption that the use of a fibrin patch, according to its base rich in fibrin, prevents bile leakage, occluding the biliary radicals at the transection (Toti et al Dig Liver Dis. 2010).

The first clinical trial comparing a hemostatic patch (Tachosil ®) versus the standard surgical hemostasis with Argon was published by Frilling et al in 2005 (Frilling et al Langenbecks Arch Surg. 2005). It was observed a reduction in the intraoperative time for hemostasis and less posterior drain in the Tachosil ® group (N = 121).

In 2007, Figueras et al (Figueras et al Ann Surg 2007) published the results of a randomized clinical trial comparing the fibrin glue administration (Tissucol ® + collagen sponge) versus control in 300 patients. The results showed no differences between groups in blood loss, transfusions, and incidence of biliary fistula, and therefore it was concluded that the cessation of the use of fibrin sealant would be a justified saving cost.

In the clinical trial recently published by Moench et al (Langenbecks Arch Surg. 2014) they studied the intraoperative time of hemostasis evaluated at 3 minutes by a non-inferiority design. The collagen hemostatic agent Sangustop ® proved to be as effective as the fibrinogen and thrombin sponge Tachosil ® in times of intraoperative hemostasis (n = 128).

The different results observed among studies may be due to the diversity of the agents evaluated, the poor standardization of the application techniques, and especially by the clinical differences.

Hemopatch® is indicated as a hemostatic device in procedures when the surgical control of bleeding by pressure, ligation, or conventional methods is inefficient or impractical. It consists in a soft, thin, foldable, and flexible collagen patch derived from bovine skin, and NHS-PEG coated (pentaerythritol polyethylene glycol ether tetrasuccinimidil glutarate). The white face, which is applied on the tissue, is covered with a thin layer of NHS-PEG providing a firm adherence to it, thus sealing the bleeding surface and inducing hemostasis at the same time. Because of its flexible structure, the application of Hemopatch ® on the site to achieve hemostasis is easily controlled. The uncoated side is marked with blue squares of a biocompatible dye, to differentiate it from the coated side.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
250
Inclusion Criteria
  • Scheduled major or minor liver resection surgery by laparotomy approach.
  • Age>18
  • They have given their written consent voluntarily after having offered the possibility of their participation in the study.
Exclusion Criteria
  • Pregnancy and lactation
  • Patients with urgent surgery
  • Concomitant surgery of another organ
  • Gallbladder or biliary-enteric anastomosis associated.
  • ALPPS surgery (stands for Associating Liver Partition and Portal vein Ligation for Staged hepatectomy).
  • Patients with liver transplantation history.
  • Patients with previous liver trauma.
  • Patients with congenital haematological disease involving clotting factors alteration.
  • Patients with known hypersensitivity to bovine proteins and brilliant blue colorante (FD&C Nº1).

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
ControlControlIn the control group (group A) no additional treatment will be applied after performing the usual surgical hemostasis.
HemopatchHemopatchHemopatch will be apply in the treatment group (group B), once the standard surgical hemostasis is achieved
Primary Outcome Measures
NameTimeMethod
BleedingDay 0 to day 30 (+-10 days)

Bleeding is defined as the fall of \> 3 g/dl of hemoglobin in the postoperative as compared to the baseline value after the operation (the hemoglobin level immediately after surgery) and/or any postoperative transfusion of red blood cells packages because of hemoglobin drop and/or the need for reoperation to stop the bleeding (e.g., embolization or re- laparotomy).

Presence of Biliary FistulaDay 0 to day 30 (+-10 days)

Biliary fistula is defined as the presence of high bilirubin levels (Bilirubin\> 3x in serum level measured at the same time) in the abdominal drainage, being included the need for interventional radiology due to biliary collection or a re-laparotomy due to biliary fistula (Brooke-Smith et al HPB 2015).

Secondary Outcome Measures
NameTimeMethod
AlcoholPreoperative
DiuresisUp to 30 days after surgery
HypertensionPreoperative
AgePreoperative
Body Mass Index (BMI)Preoperative
GenderPreoperative
Medical history (heart disease, lung disease, cirrhosis)Preoperative
DyslipemiaPreoperative
TobaccoPreoperative
Characteristics of liver diseasePreoperative

Characteristics of liver disease: benign-malignant (source)

Infection or wound dehiscence30 days after surgery
Preoperative Chemotherapy AdministrationPreoperative

Up to 30 days after surgery

immunosuppressive therapyPreoperative
Need of transfusionDay 0 to day 30 (+-10 days)

blood / plasma / platelet d. intraoperative / postoperative e. blood / plasma / platelet f. concentrates number

Incidence of re-interventions30 days after surgery

Incidence of re-interventions (No / Yes / Number / match)

Interventional radiology procedures30 days after surgery

Number of interventional radiology procedures needed and findings

Type of surgeryOn surgery

Type of surgery: Number-size of hemostatic patches used as well as their location

Postoperative liver failureDay 5 after surgery
Hospital stay (HS)Up to 30 days after surgery

Hospital stay (HS) defined as number of days from the preoperative admission to discharge.

Mortality30 days after surgery

Mortality p.o. (defined as the existence of the event within 30 days p.o.).

ReadmissionsFrom hospital discharge to 30 days after.

Readmissions (No / Yes / number of days of re-entry / Cause).

Blood preassureUp to 30 days after surgery
Concomitant medicationUp to 30 days after surgery
TemperatureUp to 30 days after surgery

Trial Locations

Locations (1)

Hospital Universitario y Politécnico La Fe

🇪🇸

Valencia, Spain

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