Efficacy of fibrin sealant in reducing resection surface crelated complications after partial liver resections

ISRCTN ISRCTN85205641
DOI https://doi.org/10.1186/ISRCTN85205641
Secondary identifying numbers N/A
Submission date
18/02/2010
Registration date
28/05/2010
Last edited
19/09/2012
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Surgery
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof Robert Porte
Scientific

Chief Department of Hepatobiliary Surgery and Liver Transplantation
University Medical Center Groningen
PO Box 30001
Groningen
9700 RB
Netherlands

Email r.j.porte@chir.umcg.nl

Study information

Study designNational multicentre prospective randomised controlled trial
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Hospital
Study typeTreatment
Participant information sheet Not available in web format, please contact m.t.de.boer@chir.umcg.nl to request a patient information sheet (Dutch only)
Scientific titleEfficacy of fibrin sealant in reducing resection surface crelated complications after partial liver resections (FRESCO trial): A Dutch, multicentre, prospective, randomised, controlled trial
Study acronymFRESCO trial
Study objectivesThe application of fibrin sealant to the cut surface of the liver remnant and to the diaphragm after elective hepatic resection will decrease the incidence of resection surface-related complications and diaphragm-related complications.
Ethics approval(s)Medical Ethical Board of University Medical Center Groningen approved on the 12th October 2005 (ref: 2005/183)
Health condition(s) or problem(s) studiedPartial liver resection complications
InterventionRandomisation to treatment group will be performed using a sealed envelope and will be performed prior to peritoneal closure after completion of conventional hemostasis and bile stasis. Only the surgeon cannot be blinded to one of two groups. Patients, ward staff and radiologists will be blinded for study medication. Stratification will be done by diagnosis: benign versus malignant.

The fibrin sealant that used in this study is Quixil® Human Surgical Sealant Kit (hereinafter called Quixil®). It consists of a packet containing two components in separate vials of 5 ml. Vial I contains Biological Active Component (BAC): a concentrate of human clottable fibrinogen at a concentration of 40 - 60 mg/ml. A synthetic antifibrinolytic agent, tranexamic acid (85 - 105 mg/ml) is added to the fibrinogen as a stabiliser. Vial II consists of a high concentration of human thrombin (800 - 1200 IU/ml) dissolved in a solution of 5.6 – 6.2 mg/ml of calcium chloride. Both components undergo double viral-inactivation steps: treatment with solvent detergent followed by pasteurisation (at 60 degrees Celsius for ten hours) for the fibrinogen and nanofiltration for the thrombin. Quixil® is provided by the manufacturer in a 10 ml double-syringe spray-device.

Group 1:
After liver resection and completion of hemostasis the envelope is opened showing treatment arm. Maximum 5 ml of fibrin sealant is sprayed or dripped on the resection surface of the liver. Maximum 5 ml of fibrin sealant is sprayed on the bare diaphragmatic resection surface. Preferably a drain will be placed adjacent to the cut liver surface.

Group 2:
After liver resection and completion of hemostasis the envelope is opened showing control arm. Preferably a drain will be placed adjacent to the cut liver surface.

Duration of treatment: single application during operation when patient is randomised in treatment arm. Total duration of follow-up will be 30 days.

For calculation of the required study-population size, resection surface-related complications such as bleeding, biloma and/or abscess formation are considered the most important target variables. Based on experience and publications of several centres, the overall proportion of these complications is estimated to be 15-20% when no fibrin sealant is applied to the resection surface (control group). A difference of about 50% between the control group and the fibrin sealant group is regarded as clinically significant. This would result in a proportion of 7.5-10% resection surface-related complications in the fibrin sealant group. Based on these assumptions, we calculated that a study size of 220 patients in each group will be needed to achieve 80% power at the 5% significance level. To have some safety margins it was decided to enrol 250 patients in each group.

The primary endpoint of this study, however, will not only be the clinical presentation of a resection surface related complication, but also all CT scan detected complications. Although the exact incidence of CT scan detected complications is not known, this is expected to be higher than that of clinically detected complications. Therefore, an interim analysis will be performed after 180 patients (90 in each group). Main reason to do an interim analysis is to investigate weather the assumed complication rate is indeed 15 to 20%, or much higher. If the complication rate is higher, a smaller number of patients will be required to obtain the same level of statistical power as outlined above.

An interim analysis was performed in November 2009 after we had the completed CRF’s of 180 patients enrolled in the FRESCO trial. An independent epidemiologist analysed the complication rate in the control group. This complication rate was higher than expected: 30,4%. Based on the complication percentage of 30.4% and on the assumption that a difference of 50% between the control group and the fibrin sealant group is clinically significant, a study size of 131 patients in each group will be needed to achieve a 80% power at the 5% significance level. To have some safety margins it was decided to enrol 300 patients in total.
Intervention typeProcedure/Surgery
Primary outcome measure1. Resection surface related complications detected by computed tomography (CT) scan or clinical symptoms: haematoma, biloma or subphrenic abscess
2. Diaphragm related complications detected by CT scan or clinical symptoms: pleural effusion
3. Need for reintervention for bleeding or bile leakage from the cut surface of the liver, or pleural effusion

CT scan after 7 days, further assessment of complications and reinterventions during hospital stay until first out-patient appointment.
Secondary outcome measures1. Changes in drain bilirubin (micromol/l), drain hemoglobin concentration (mmol/l) and volume of fluid drainage (ml) from the abdominal drains during the first three days post-operatively
2. Decrease in serum haemoglobin concentration (mmol/l) (lab day 1, 3, 5, 7, thereafter weekly)
3. Transfusion requirement (whole admission until first outpatient appointment)
4. Post-operative morbidity (whole admission until outpatient appointment)
5. Post-operative mortality (whole admission until outpatient appointment)
6. Length of hospital stay (whole admission until outpatient appointment)
Overall study start date23/05/2006
Completion date01/06/2010

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexBoth
Target number of participants600
Key inclusion criteria1. Patients aged greater than or equal to 18 years, either sex
2. Undergo liver resections (at least one segment) for benign or malignant tumours or metastatic tumours, or
3. Undergo liver resection in combination with radiofrequency ablation (RFA)
Key exclusion criteria1. Aged less than 18 years
2. Undergo liver resections with extrahepatic biliary resection and reconstruction (Klatskin tumours)
3. Cirrhosis
4. Other disorders of haemostasis
5. Polycystic liver disease
6. Any associated operative gastrointestinal procedures (a needle catheter jejunostomy is not excluded)
7. Wedge resections
8. Pregnancy
9. History of hypersensitivity, allergy or anaphylactic reaction to any plasma derived product, including fibrin sealant
Date of first enrolment23/05/2006
Date of final enrolment01/06/2010

Locations

Countries of recruitment

  • Netherlands

Study participating centre

Chief Department of Hepatobiliary Surgery and Liver Transplantation
Groningen
9700 RB
Netherlands

Sponsor information

Johnson and Johnson Medical Limited (UK)
Industry

Kirkton Campus
Simpson Parkway
Livingston
EH54 7AT
United Kingdom

Website http://www.jnj.com/connect/
ROR logo "ROR" https://ror.org/03qwpn290

Funders

Funder type

Hospital/treatment centre

University Medical Center Groningen (UMCG) (Netherlands) - local hospital committee performance audit (Doelmatigheidsonderzoek) funding

No information available

Johnson and Johnson Medical Limited (UK) - supplying fibrin sealant and funding of CT scans at one week post-operative

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing plan

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Results article results 01/08/2012 Yes No