Ignite Creation Date:
2024-05-05 @ 5:23 PM
Last Modification Date:
2024-10-26 @ 9:31 AM
Study NCT ID:
NCT00440921
Status:
WITHDRAWN
Last Update Posted:
2015-06-02
First Post:
2007-02-26
Brief Title:
Clinical Trial for Fibrin Sealant in Knee Surgery
Sponsor:
Sanquin Research Blood Bank Divisions
Organization:
Sanquin Research Blood Bank Divisions
Study Overview
Official Title:
Randomized Clinical Trial for Fibrin Sealant in Knee Surgery
Status:
WITHDRAWN
Status Verified Date:
2015-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
No agreement between investigator and sponsor
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Thermogenesis is a company that sells a machine for the production of fibrin sealant of single donor plasma the CryoSeal Fibrin Sealant System CS-1
Fibrin sealant consists of two components cryoprecipitate and thrombin Cryoprecipitate is the fraction of human plasma that contains concentrated coagulation factors such as fibrinogen Thrombin is an enzyme that facilitates the conversion of fibrinogen into fibrin so that a clot will be formed
Fibrin sealant can be used in surgery to increase hemostasis in the wound after eg knee- or hip replacement cosmetical surgery or partial liverresections
Until now mainly autologous plasma was used to produce fibrin sealant with the CS-1 Within Sanquin there is a question whether fibrin sealant can be produced from the allogeneic quarantaine plasma that is in stock Therefore in this study will be studied whether allogenous single donor fibrin sealant produced using the CS-1 is effective in wound healing and as consequence of this can be registered as a product of Sanquin To answer these questions a national working party is formed working party Fibrin Sealant
So far three man personnel in Sanquin Blood Bank Nort East Region SBNO are certified by Thermogenesis to use the CS-1 for production of fibrin sealant and an in vitro validation has been performed
The next step will be a study for the in vivo effectiveness of fibrin sealant produced of single donor allogeneic quarantaine plasma using the CS-1 As control patients without fibrin sealant treatment will be studied Two hospitals Refaja Hospital in Stadskanaal and Wilhelmina hospital in Assen are already interested in participating in this study Probably three more hospitals will participate
The use of fibrin sealant will be studied in a prospective randomized trial for patients undergoing knee and hip replacements
Fibrin sealant consists of two components cryoprecipitate and thrombin Cryoprecipitate is the fraction of human plasma that contains concentrated coagulation factors such as fibrinogen Thrombin is an enzyme that facilitates the conversion of fibrinogen into fibrin so that a clot will be formed
Fibrin sealant can be used in surgery to increase hemostasis in the wound after eg knee- or hip replacement cosmetical surgery or partial liverresections
Until now mainly autologous plasma was used to produce fibrin sealant with the CS-1 Within Sanquin there is a question whether fibrin sealant can be produced from the allogeneic quarantaine plasma that is in stock Therefore in this study will be studied whether allogenous single donor fibrin sealant produced using the CS-1 is effective in wound healing and as consequence of this can be registered as a product of Sanquin To answer these questions a national working party is formed working party Fibrin Sealant
So far three man personnel in Sanquin Blood Bank Nort East Region SBNO are certified by Thermogenesis to use the CS-1 for production of fibrin sealant and an in vitro validation has been performed
The next step will be a study for the in vivo effectiveness of fibrin sealant produced of single donor allogeneic quarantaine plasma using the CS-1 As control patients without fibrin sealant treatment will be studied Two hospitals Refaja Hospital in Stadskanaal and Wilhelmina hospital in Assen are already interested in participating in this study Probably three more hospitals will participate
The use of fibrin sealant will be studied in a prospective randomized trial for patients undergoing knee and hip replacements
Detailed Description:
1 Introduction
Until now mainly autologous plasma was used to produce fibrin sealant with the CS-1 Within Sanquin there is a question whether fibrin sealant can be produced from the allogeneic quarantaine plasma that is in stock Therefore in this study will be studied whether allogenous single donor fibrin sealant produced using the CS-1 is effective in wound healing and as consequence of this can be registered as a product of Sanquin
The use of fibrin sealant will be studied in a prospective randomized trial for patients undergoing knee and hip replacements
2 Aim
To study the effectiveness of fibrin sealant produced of single donor allogeneic plasma when used intra-operatively after total knee or hip replacement
Primairy endpoint wound healing
Secondary endpoints total blood loss until 24h post-operative amount of blood transfused motion of the joint knee after surgery amount of pain after surgery use of antibiotics wound infections stay in hospital adverse events satisfaction with fibrin sealant as used by the physician
3 Hypothesis
We hypothesize that use of fibrin sealant will have a positive effect on wound healing will cause less blood loss decreased use of antibiotics and and will cause that a decreased number of infections will be seen compared to patients who are not treated with fibrin sealant Through this hospital stay will probably be shortened for patients who are treated with fibrin sealant
As a working hypothesis we assume a score for wound healing of at least 20 lower and at least 20 less blood loss for the fibrin sealant treated group
4 Definitions
NA
5 Ethical aspects 51 Admission of the Ethical Committee For this study approval is asked from the ethical committee of each participating hospital
52 Admission of the patient
Each patient who potentially can be included will be asked with informed consent for admission and participation in the study
53 Confidentiality
Patients will be registered using a patient number date of birth and study number and further will be anonimized
54 Input Data
Input of data will be done by the senior researcher OO of SBNO Shehe will take confidentiality of the data into account
6 Materials and collaborating departments
Orthopedic Surgery department of hospitals
Patient data can be filled in on the forms in the appendix
Fibrin Sealant data can be filled in on the form in the appendix
Department OO of SBNO for analysis of data
SBNO for production and release of fibrin sealant
7 Patients 71 Inclusion
Age minimum of 18 years
Gender man or woman
Admission of the patient after informed consent 72 Exclusion
Liver failure
Congenital or acquired coagulation disorders
Thrombocytopenia 100 x109PLTL 73 Number of patients
The number of patients needed in this study to indicate a statistical significantly difference can be calculated from a pilot study for wound healing in patients that have undergone knee- or hip replacement
Knee replacement For calculation of the number of patients we aim to see a significant difference of at least 20 better wound healing after use of fibrin sealant during surgery From a pilot we observed for wound healing a score of 071049 With the power at 80 and alpha at 005 we need 193 evaluable patients in both study group fibrin sealant treated and control group non fibrin sealant treated
Hip replacement For calculation of the number of patients we aim to see a significant difference of at least 20 better wound healing after use of fibrin sealant during surgery From a pilot we observed for wound healing a score of 158079 With the power at 80 and alpha at 005 we need 96 evaluable patients in both study group fibrin sealant treated and control group non fibrin sealant treated
8 Adverse events
Each adverse event AE that occurs during of after the use of fibrin sealant will be noted on the form by the physician on duty
An AE is any untoward medical occurrence in a patient patient is defined as any subject who has been enrolled in the study as evidenced by the subject having signed informed consent or any unfavorable and unintended sign for example an abnormal laboratory finding symptom or disease that occurs during the course of the clinical investigation The AE may or may not be considered as related to the investigational drug or device All AEs should be recorded in the patients chart and graded mild moderate or severe All AEs shall be handled to the hospital procedures in force and as soon as possible passed down to the study coordinators in case of fatality at least within 24h
Mild Symptom barely noticeable to patient does not influence performance or functioning Prescription drugs not ordinarily needed for relief of symptom but may be given because of personality of patient
Moderate Symptom of sufficient severity to make patient uncomfortable performance of daily activities influenced patient is able to continue in study treatment for symptom is needed
Severe Symptom causes severe discomfort or may be of such severity that patient cannot perform daily routines may cause cessation of treatment with fibrin sealant or even may be fatal
After complementary follow-up the physician on duty will conclude with notice of argumentation whether the AE
is not caused by fibrin sealant
is possible but not necessary caused by fibrin sealant causes cannot be proven nor excluded
is probably caused by fibrin sealant
is certainly caused by fibrin sealant
9 Procedure 91 Set up clinical trial
The study is a randomized prospective clinical trial
Fibrin sealant treated patients will be compared with non fibrin sealant treated patients
Patients included undergo total knee or hip replacement
During participation of the patient only the study coordinator of the hospital and the staff of the operation room know whether a patient is treated with fibrin sealant or not
Nurses and patients can be informed at the end of participation of the patient at discharge of the hospital
Primairy endpoint is wound healing
Secondary endpoints are total blood loss until 24h post-operative amount of blood transfused motion of the joint knee after surgery amount of pain after surgery use of antibiotics wound infections stay in hospital adverse events satisfaction with fibrin sealant as used by the physician
Each group fibrin sealant treated and non fibrin sealant treated wil contain 193 patients for knee and 96 patients for hip surgery
92 Production and release of fibrin sealant
Fibrin sealant will be produced and released from SBNO according to the procedures in force
93 Controled treatment with fibrin sealant
Each patient who might be included see 71 and 72 will be asked for admission to participate in this study by informed consent prior to surgery Therefore a letter with information about this study will be given to each patient who might be included
After admission an envelope will be openend by the study coordinator in the hospital in which a code is for treatment or no treatment with fibrin sealant The study coordinator will tell the outcome only to the personel of the OR who need to know it for preparation and usage of the fibrin sealant People from the operation room do not communicate this outcome to the nursery Except for treatment with fibrin sealant there will be no difference in treatment of the patients
Patient and nurses when desired will be informed about treatment with fibrin sealant or not when the patient leaves the hospital and is discharged from this study
Prior to surgery a blood sample of the patient will be taken to determine the platelet count hematocrit and hemoglobin
Fibrin sealant if used will be assessed just before closing the wound 94 Parameters
The following parameters of patients and surgery will be noted pre-operative by nurses double blinded
Birth date gender
Weight length
Platelet count haemoglobin and hematocrit
Underlying diseases
Medication
Use of antibiotics
Pain VASC via standardized score Score 0 no pain 2 pain that can be neglected 4 uncomfortable pain 6 painful cannot be neglected 8 very painful patient cannot concentrate himherself 10 extreme painful patient cannot do anything
The following parameters of patients and surgery will be noted per-operative by staff of the operation room single blinded
Time points of start surgery treatment with fibrin sealant and end of surgery
Hemostasis of fibrin sealant seen yes or no only for hip replacement because it is hard to see this for knee replacement
Medication
Use of antibiotics
Number of transfusions red cells platelets and plasma
Adverse events severeness and relation to treatment with fibrin sealant
Mobility of knee only for knee replacement
The following parameters of patients and surgery will be noted at 1h post-operative by staff of operation room single blinded
Blood loss via drain
Medication
Use of antibiotics
Number of transfusions red cells platelets and plasma
Adverse events severeness and relation to treatment with fibrin sealant
Pain VASC at 1h after end of anaesthesia via standardized score see above under parameters pre-operative
The following parameters of patients and surgery will be noted 1h post-operative by the nurses double blinded
Wound healing including wound leakage and wound infection via score form see appendix at time of wound treatment in case of heavy wound leakage ie bandage need to be changed at 3 days postoperatively and at discharge from hospital
Blood loss via drain at removing of the drain mostly the next morning after surgery
Medication until discharge of hospital
Use of antibiotics until discharge from hospital
Number of transfusions red cells platelets and plasma until discharge from hospital
Adverse events severeness and relation to treatment with fibrin sealant until discharge from hospital
Pain VASC at 3h post operative at 2100 h day of surgery at 800 h 1400 h and 2100 h at day after surgery at 800 h on the second day after surgery and at discharge from hospital as described above under parameters pre-operative
Mobility of knee at discharge from hospital Also date at which 90 flexion is reached will be noted
Hospital stay after surgery in days
10 Analyzing and reporting of results 101 Analyzing results
Anonimized patient data will be put in and analyzed in an Excel file
Results of knee and hip replacements will be analyzed and reported separately
Via an unpaired t-test differences in primary and secondary endpoints between fibrin sealant treated and non fibrin sealant treated patients will be studied
The Fishers exact test will be used to determine the effect of use of fibrin sealant in wound leakage wound infections and undesired events
Of the results a report will be written Also a report for data of each separate hospital will be written Results about knee and hip replacements will described separately
11 Time scheduling
The study will start in January 2007 After minimaal 193 evaluable patients per group for knee surgery 193 patients treated with fibrin sealant and 193 patients not treated with fibrin sealant and minimal 96 evaluable patients per group for hip surgery 96 patients treated with fibrin sealant and 96 patients not treated with fibrin sealant the study will be finished
It is expected that this study will take about 1 year in case 5 hospitals participate
Only in case of serious reasons eg severe adverse events the study will be terminated early
Until now mainly autologous plasma was used to produce fibrin sealant with the CS-1 Within Sanquin there is a question whether fibrin sealant can be produced from the allogeneic quarantaine plasma that is in stock Therefore in this study will be studied whether allogenous single donor fibrin sealant produced using the CS-1 is effective in wound healing and as consequence of this can be registered as a product of Sanquin
The use of fibrin sealant will be studied in a prospective randomized trial for patients undergoing knee and hip replacements
2 Aim
To study the effectiveness of fibrin sealant produced of single donor allogeneic plasma when used intra-operatively after total knee or hip replacement
Primairy endpoint wound healing
Secondary endpoints total blood loss until 24h post-operative amount of blood transfused motion of the joint knee after surgery amount of pain after surgery use of antibiotics wound infections stay in hospital adverse events satisfaction with fibrin sealant as used by the physician
3 Hypothesis
We hypothesize that use of fibrin sealant will have a positive effect on wound healing will cause less blood loss decreased use of antibiotics and and will cause that a decreased number of infections will be seen compared to patients who are not treated with fibrin sealant Through this hospital stay will probably be shortened for patients who are treated with fibrin sealant
As a working hypothesis we assume a score for wound healing of at least 20 lower and at least 20 less blood loss for the fibrin sealant treated group
4 Definitions
NA
5 Ethical aspects 51 Admission of the Ethical Committee For this study approval is asked from the ethical committee of each participating hospital
52 Admission of the patient
Each patient who potentially can be included will be asked with informed consent for admission and participation in the study
53 Confidentiality
Patients will be registered using a patient number date of birth and study number and further will be anonimized
54 Input Data
Input of data will be done by the senior researcher OO of SBNO Shehe will take confidentiality of the data into account
6 Materials and collaborating departments
Orthopedic Surgery department of hospitals
Patient data can be filled in on the forms in the appendix
Fibrin Sealant data can be filled in on the form in the appendix
Department OO of SBNO for analysis of data
SBNO for production and release of fibrin sealant
7 Patients 71 Inclusion
Age minimum of 18 years
Gender man or woman
Admission of the patient after informed consent 72 Exclusion
Liver failure
Congenital or acquired coagulation disorders
Thrombocytopenia 100 x109PLTL 73 Number of patients
The number of patients needed in this study to indicate a statistical significantly difference can be calculated from a pilot study for wound healing in patients that have undergone knee- or hip replacement
Knee replacement For calculation of the number of patients we aim to see a significant difference of at least 20 better wound healing after use of fibrin sealant during surgery From a pilot we observed for wound healing a score of 071049 With the power at 80 and alpha at 005 we need 193 evaluable patients in both study group fibrin sealant treated and control group non fibrin sealant treated
Hip replacement For calculation of the number of patients we aim to see a significant difference of at least 20 better wound healing after use of fibrin sealant during surgery From a pilot we observed for wound healing a score of 158079 With the power at 80 and alpha at 005 we need 96 evaluable patients in both study group fibrin sealant treated and control group non fibrin sealant treated
8 Adverse events
Each adverse event AE that occurs during of after the use of fibrin sealant will be noted on the form by the physician on duty
An AE is any untoward medical occurrence in a patient patient is defined as any subject who has been enrolled in the study as evidenced by the subject having signed informed consent or any unfavorable and unintended sign for example an abnormal laboratory finding symptom or disease that occurs during the course of the clinical investigation The AE may or may not be considered as related to the investigational drug or device All AEs should be recorded in the patients chart and graded mild moderate or severe All AEs shall be handled to the hospital procedures in force and as soon as possible passed down to the study coordinators in case of fatality at least within 24h
Mild Symptom barely noticeable to patient does not influence performance or functioning Prescription drugs not ordinarily needed for relief of symptom but may be given because of personality of patient
Moderate Symptom of sufficient severity to make patient uncomfortable performance of daily activities influenced patient is able to continue in study treatment for symptom is needed
Severe Symptom causes severe discomfort or may be of such severity that patient cannot perform daily routines may cause cessation of treatment with fibrin sealant or even may be fatal
After complementary follow-up the physician on duty will conclude with notice of argumentation whether the AE
is not caused by fibrin sealant
is possible but not necessary caused by fibrin sealant causes cannot be proven nor excluded
is probably caused by fibrin sealant
is certainly caused by fibrin sealant
9 Procedure 91 Set up clinical trial
The study is a randomized prospective clinical trial
Fibrin sealant treated patients will be compared with non fibrin sealant treated patients
Patients included undergo total knee or hip replacement
During participation of the patient only the study coordinator of the hospital and the staff of the operation room know whether a patient is treated with fibrin sealant or not
Nurses and patients can be informed at the end of participation of the patient at discharge of the hospital
Primairy endpoint is wound healing
Secondary endpoints are total blood loss until 24h post-operative amount of blood transfused motion of the joint knee after surgery amount of pain after surgery use of antibiotics wound infections stay in hospital adverse events satisfaction with fibrin sealant as used by the physician
Each group fibrin sealant treated and non fibrin sealant treated wil contain 193 patients for knee and 96 patients for hip surgery
92 Production and release of fibrin sealant
Fibrin sealant will be produced and released from SBNO according to the procedures in force
93 Controled treatment with fibrin sealant
Each patient who might be included see 71 and 72 will be asked for admission to participate in this study by informed consent prior to surgery Therefore a letter with information about this study will be given to each patient who might be included
After admission an envelope will be openend by the study coordinator in the hospital in which a code is for treatment or no treatment with fibrin sealant The study coordinator will tell the outcome only to the personel of the OR who need to know it for preparation and usage of the fibrin sealant People from the operation room do not communicate this outcome to the nursery Except for treatment with fibrin sealant there will be no difference in treatment of the patients
Patient and nurses when desired will be informed about treatment with fibrin sealant or not when the patient leaves the hospital and is discharged from this study
Prior to surgery a blood sample of the patient will be taken to determine the platelet count hematocrit and hemoglobin
Fibrin sealant if used will be assessed just before closing the wound 94 Parameters
The following parameters of patients and surgery will be noted pre-operative by nurses double blinded
Birth date gender
Weight length
Platelet count haemoglobin and hematocrit
Underlying diseases
Medication
Use of antibiotics
Pain VASC via standardized score Score 0 no pain 2 pain that can be neglected 4 uncomfortable pain 6 painful cannot be neglected 8 very painful patient cannot concentrate himherself 10 extreme painful patient cannot do anything
The following parameters of patients and surgery will be noted per-operative by staff of the operation room single blinded
Time points of start surgery treatment with fibrin sealant and end of surgery
Hemostasis of fibrin sealant seen yes or no only for hip replacement because it is hard to see this for knee replacement
Medication
Use of antibiotics
Number of transfusions red cells platelets and plasma
Adverse events severeness and relation to treatment with fibrin sealant
Mobility of knee only for knee replacement
The following parameters of patients and surgery will be noted at 1h post-operative by staff of operation room single blinded
Blood loss via drain
Medication
Use of antibiotics
Number of transfusions red cells platelets and plasma
Adverse events severeness and relation to treatment with fibrin sealant
Pain VASC at 1h after end of anaesthesia via standardized score see above under parameters pre-operative
The following parameters of patients and surgery will be noted 1h post-operative by the nurses double blinded
Wound healing including wound leakage and wound infection via score form see appendix at time of wound treatment in case of heavy wound leakage ie bandage need to be changed at 3 days postoperatively and at discharge from hospital
Blood loss via drain at removing of the drain mostly the next morning after surgery
Medication until discharge of hospital
Use of antibiotics until discharge from hospital
Number of transfusions red cells platelets and plasma until discharge from hospital
Adverse events severeness and relation to treatment with fibrin sealant until discharge from hospital
Pain VASC at 3h post operative at 2100 h day of surgery at 800 h 1400 h and 2100 h at day after surgery at 800 h on the second day after surgery and at discharge from hospital as described above under parameters pre-operative
Mobility of knee at discharge from hospital Also date at which 90 flexion is reached will be noted
Hospital stay after surgery in days
10 Analyzing and reporting of results 101 Analyzing results
Anonimized patient data will be put in and analyzed in an Excel file
Results of knee and hip replacements will be analyzed and reported separately
Via an unpaired t-test differences in primary and secondary endpoints between fibrin sealant treated and non fibrin sealant treated patients will be studied
The Fishers exact test will be used to determine the effect of use of fibrin sealant in wound leakage wound infections and undesired events
Of the results a report will be written Also a report for data of each separate hospital will be written Results about knee and hip replacements will described separately
11 Time scheduling
The study will start in January 2007 After minimaal 193 evaluable patients per group for knee surgery 193 patients treated with fibrin sealant and 193 patients not treated with fibrin sealant and minimal 96 evaluable patients per group for hip surgery 96 patients treated with fibrin sealant and 96 patients not treated with fibrin sealant the study will be finished
It is expected that this study will take about 1 year in case 5 hospitals participate
Only in case of serious reasons eg severe adverse events the study will be terminated early
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None