FIRST study

Study Title 

The use of Fibrin Sealant in total knee replacement surgery trial (FIRST).

Background

Fibrin Sealant, also referred to as “fibrin glue” consists of two components, one component is thrombin and the other one is cryoprecipitate with fibrinogen. When both components are combined the last step of the coagulation cascade is started; the conversion of fibrinogen in fibrin. CryoSeal can be used at the end of the operation to seal the bare bony surfaces (i.e. bone surfaces not covered by the prosthesis), and synovial tissue with the aim to decrease or prevent large postoperative bleeding at the surgical field. The patient’s coagulation system is also capable to stop excessive bleeding, but this will probably take longer. CryoSeal only fastens this process because of the higher amount of growth factors; it imitates the last phase of the coagulation process. 

Is the application of CryoSeal (CS) by primary total knee replacement surgery beneficial for the patient with respect to a faster track and improved early (2 and 6 weeks) postoperative rehabilitation as determined by improved knee extension and flexion? The beneficial effect may be due to quicker rehabilitation (focus on knee function), by pain reduction, better mobilization and improved quality of life (especially short term). 

The study is a randomized, multi centre trial in orthopedic surgery in patients who receive a primary total knee replacement. Patients will be randomized in two groups. The intervention group will be treated with CryoSeal per operative and the control group will receive standard care (no additional treatment during surgery). Patients will be stratified prior to randomization in two groups depending on the postoperative use of a wound drain. No consensus exists on the usage of the latter.

Rationale

Fibrin Sealant is known to have some potential benefits for intra-operative use, especially in the acceleration of the coagulation cascade. Most studies with fibrin glue are focusing on the reduction of allogenic blood transfusion and the possibilities to reduce costs. Firstly, fibrin sealant was made from patients’ blood plasma but the logistic problems made introduction in general hard. Nowadays Sanquin has produced a CryoSeal (fibrin sealant) made of single-donor plasma which can be used during surgery.

Study objective

Is the application of CryoSeal (CS) in primary total knee replacement surgery beneficial for the patient with respect to a faster track and improved postoperative rehabilitation? The beneficial effect may be due to quicker functional knee rehabilitation, by pain reduction, better mobilization and improved quality of life during the early postoperative period.

Sponsors 

Sanquin Blood Supply Foundation.

Study design

A prospective, randomized multi center study.

Subjects and Sites 

Patients aged above 18 years scheduled for primary total knee replacement because of osteoarthritis or rheumatic arthritis, meeting all the inclusion criteria and none of the exclusion criteria, are eligible for inclusion in the study.  At present time, 6 centers enroll patients. Since total knee replacement surgery is a well defined standardized surgical procedure and CS application can be standardized on the amount and the well defined layers of femoral and tibial and patellar ‘if applicable’.

Intervention

The intervention is the application of CS during surgery according to the standardized manner. The control group will receive standard care.

Main endpoints

Primary

• Flexion- and extension knee function after 2 and 6 weeks.

Secondary

• Postoperative complications, pain score, knee function Flexion/Extension, Barthel score (day 3);
• Outpatient department scores (2 weeks, 6 weeks and 3 months, 1 year): Complications, pain score, knee function, OKS, KSS, KOOS, SF-12, IPQ-K and EQ5D

Inclusion criteria

• Patients who will undergo primary total knee replacement surgery for osteoarthritis or rheumatic arthritis
• Age, minimum of 18 years
• ASA classification I-III

Exclusion criteria

• Liver failure
• Congenital or acquired coagulation disorders
• Patients with known haemophilia or von Willibrand disease
• Patients with INR >2 (standard practice for operation)