Clinical trial NCT02769754: Effectiveness of the Use of the New Hemostatic Patch Hemopatch ® in Patients Undergoing Surgical Liver Resection
Official title: Phase III, Randomized, Unblinded, Controlled Clinical Trial for Evaluating the Effectiveness of the Use of the New Hemostatic Patch Hemopatch ® in Patients Undergoing Surgical Liver Resection
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Liver Damage
Surgery
Keywords: LIVER
RESECTION
SURGERY
Lead sponsor: Instituto de Investigacion Sanitaria La Fe
Sponsor class: OTHER
First posted: 2016-05-12
Enrollment: 250
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.

Eligibility criteria: 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).

Primary outcomes:
measure: Bleeding
timeFrame: Day 0 to day 30 (+-10 days)
measure: Presence of Biliary Fistula
timeFrame: Day 0 to day 30 (+-10 days)
Secondary outcomes:
measure: Age
timeFrame: Preoperative
measure: Body Mass Index (BMI)
timeFrame: Preoperative
measure: Gender
timeFrame: Preoperative
measure: Medical history (heart disease, lung disease, cirrhosis)
timeFrame: Preoperative
measure: Hypertension
timeFrame: Preoperative
measure: Dyslipemia
timeFrame: Preoperative
measure: Tobacco
timeFrame: Preoperative
measure: Alcohol
timeFrame: Preoperative
measure: Characteristics of liver disease
timeFrame: Preoperative
measure: Type of surgery
timeFrame: On surgery
measure: Type of surgery
timeFrame: On surgery
measure: Type of surgery
timeFrame: On surgery
measure: Need of transfusion
timeFrame: Day 0 to day 30 (+-10 days)
measure: Need of transfusion
timeFrame: Day 0 to day 30 (+-10 days)
measure: Incidence of re-interventions
timeFrame: 30 days after surgery
measure: Postoperative liver failure
timeFrame: Day 5 after surgery
measure: Infection or wound dehiscence
timeFrame: 30 days after surgery
measure: Interventional radiology procedures
timeFrame: 30 days after surgery
measure: Mortality
timeFrame: 30 days after surgery
measure: Hospital stay (HS)
timeFrame: Up to 30 days after surgery
measure: Readmissions
timeFrame: From hospital discharge to 30 days after.
measure: Preoperative Chemotherapy Administration
timeFrame: Preoperative
measure: immunosuppressive therapy
timeFrame: Preoperative
measure: Diuresis
timeFrame: Up to 30 days after surgery
measure: Temperature
timeFrame: Up to 30 days after surgery
measure: Blood preassure
timeFrame: Up to 30 days after surgery
measure: Concomitant medication
timeFrame: Up to 30 days after surgery
Other outcomes:
Locations:
city: Valencia
country: Spain
facility: Hospital Universitario y Politécnico La Fe
Study officials:
affiliation: Instituto de Investigación Sanitaria La Fe
name: Rafael López-Andújar
role: PRINCIPAL_INVESTIGATOR
References: