|- candidate number||8429|
|- NTR Number||NTR2500|
|- ISRCTN||ISRCTN wordt niet meer aangevraagd.|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||9-sep-2010|
|- Secondary IDs||P10.115 METC sanquin|
|- Public Title||The use of Fibrin Sealant in total knee replacement surgery.|
|- Scientific Title||The use of Fibrin Sealant in total knee replacement surgery.|
|- ACRONYM||Cryoseal in TKR|
|- hypothesis||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. |
|- Healt Condition(s) or Problem(s) studied||Total knee replacement (TKR), Rehabilitation, Fibrin sealant|
|- Inclusion criteria||1. Patients who will undergo primary total knee replacement surgery for osteoarthritis or rheumatic arthritis;|
2. Age, minimum of 18 years;
3. (Admission of the patient after informed consent);
4. ASA classification I-III.
|- Exclusion criteria||1. Liver failure;|
2. Congenital or acquired coagulation disorders;
3. Patients with known haemophilia or von Willibrand disease;
4. Patients with INR >2 (standard practice for operation).
|- mec approval received||yes|
|- multicenter trial||yes|
|- Type||2 or more arms, randomized|
|- planned startdate ||1-jan-2011|
|- planned closingdate||1-jan-2013|
|- Target number of participants||500|
|- Interventions||The CryoSeal (CS) experimental product consists of two components: cryoprecipitate and thrombin. Cryoprecipitate is one fraction of a single human plasma donation that contains concentrated coagulation factors, such as fibrinogen, which together with the second fraction containing an enzyme thrombin, that facilitating the conversion of fibrinogen into fibrin. Together mixed they will form a clot. This product has two main advantages compared to other current available preparations, namely a single donor-exposure compared to commercial allogeneic fibrin Sealant (FS) products, produced from pooled multiple plasma donations which also has a bovine thrombin source and secondly the controlled hemostatic conditions of the product compared to autologous FS, prepared prior to surgery or at the operation theatre and which content is dependent on its hemostatic condition of patients (age, co-morbidity Based on preliminary estimations on CS use in the literature (1), 12-15 ml CS is expected to be used per patient randomized for CS.|
|- Primary outcome||Postoperative knee function in mean extension difference with goniometric at 2 and 6 weeks (in relation to secondary endpoints), corrected for pre-operative extension.|
|- Secondary outcome||1. Postoperative Hb/Ht;|
2. Number of transfusions after surgery;
3. VAS pain score;
5. Total hospital stay and duration of rehabilitation;
6. Illness perception IPQ-K score;
7. Function improvement score (KSS, Barthel Index score, KOOS);
8. Postoperative F/E.
|- Timepoints||1. Pre-operative;|
2. 2 weeks;
3. 6 weeks;
4. 1 year.
|- Trial web site||N/A|
|- status||inclusion stopped: follow-up|
|- CONTACT FOR PUBLIC QUERIES||MD. W.Chr. Verra|
|- CONTACT for SCIENTIFIC QUERIES||MD. W.Chr. Verra|
|- Sponsor/Initiator ||Sanquin Blood Bank (Stichting Sanquin Bloedvoorziening)|
(Source(s) of Monetary or Material Support)
|Sanquin Blood Supply|
|- Brief summary||Rationale: |
Fibrin Sealant is known to have some potential benefits for intraoperative use, especially in the acceleration of the coagulation cascade. Most studies with fibrin glue are focussing on the reduction of allogeneic blood transfusion and the possibilities to reduce costs. Firstly, fibrin sealant was made from patientsí blood plasma but the logistic problems made introduction in general hard. Now Sanquin has produced a CryoSeal (fibrin sealant) made of single-donor plasma which can be used during surgery. This application is already used in cardiothoracic surgery.
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 mobilisation and improved quality of life during the early postoperative period.
Multicenter, randomised controlled trial stratified by clinic.
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.
The intervention is the application of CryoSeal during surgery according to the standardised manner. The control group will receive standard care.
Main study parameters/endpoints:
Primary endpoint: Postoperative knee function in mean extension difference with goniometric at 2 and 6 weeks (in relation to secondary endpoints), corrected for pre-operative extension.
Secondary endpoints: Postoperative complications, VAS pain score, knee function Flexion/Extension, Barthel score (day 3); Outpatient department scores (2 weeks, 6 weeks and 3 months, 1 year): Complications, VAS pain knee function, KSS, KOOS, SF-12, IPQ-K and EQ5D.
Nature and extent of the burden and risks associated with participation benefit and group relatedness:
Given the origin of the CryoSeal product, i.e. donor plasma and in the absence of added bovine or chemical fibrinolysis inhibitors, no toxicity is to be expected by applying CryoSeal produced by the CS-1 (machine) / CP-3 (disposable) system, which was confirmed by pre and clinical research.
When a total sample size of 500 patients appeared to be reasonable (by the 2 wks standard deviations of the P.E.) a single interim analysis will be performed in the first 250 patients. Considering patients with and without drain, we compute the pre- and post-operative differences in extension angles as primary outcome. We compare the patients with and without Cryoseal in an analysis of variance adjusting for the pre-operative extension angles. We perform a one-sided test at level 0.0025. If we find a significant difference, we stop including patients. The study will also stop when both arms show significant increase in extension function when > 600 patients are needed.
If we do not find a significant difference, we will proceed to test for futility. In 250 patients, we perform a one-sided test at level 0.1 to determine if patients with Cryoseal show SMALLER post-operative difference in extension angles, compared to those without Cryoseal. If we reject this hypothesis, we stop the inclusion of patients.
|- Main changes (audit trail)||30-5-2013: Per May 15th 2013, an addition to the analysis plan was added to the protocol before deblinding of the database. This analysis plan describes subgroup analyses that will be performed besides the analysis on primary outcome as described in the original protocol.
A version of this analysis plan was sent to the trial registry as well.|
|- RECORD||9-sep-2010 - 30-mei-2013|