Clinical Trial Details
— Status: Withdrawn
Administrative data
| NCT number |
NCT00440921 |
| Other study ID # |
RP06.008 |
| Secondary ID |
|
| Status |
Withdrawn |
| Phase |
N/A
|
| First received |
February 26, 2007 |
| Last updated |
June 1, 2015 |
| Start date |
December 2008 |
| Est. completion date |
June 2010 |
Study information
| Verified date |
June 2015 |
| Source |
Sanquin Research & Blood Bank Divisions |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO) |
| Study type |
Interventional
|
Clinical Trial 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 e.g.
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.
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
· N/A
5. Ethical aspects 5.1 Admission of the Ethical Committee · For this study approval is
asked from the ethical committee of each participating hospital.
5.2 Admission of the patient
· Each patient who potentially can be included will be asked with informed consent for
admission and participation in the study.
5.3 Confidentiality
· Patients will be registered using a patient number, date of birth and study number
and further will be anonimized.
5.4 Input Data
· Input of data will be done by the (senior) researcher O&O of SBNO. She/he 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 O&O of SBNO for analysis of data
- SBNO for production and release of fibrin sealant
7. Patients 7.1 Inclusion
- Age, minimum of 18 years
- Gender, man or woman
- Admission of the patient after informed consent 7.2 Exclusion
- Liver failure
- Congenital or acquired coagulation disorders
- Thrombocytopenia, < 100 x10^9PLT/L 7.3 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
0.71±0.49. With the power at 80% and alpha at 0.05 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
1.58±0.79. With the power at 80% and alpha at 0.05 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 AE's should be recorded in the patient's chart
and graded mild, moderate, or severe. All AE's 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 9.1 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.
9.2 Production and release of fibrin sealant
· Fibrin sealant will be produced and released from SBNO according to the procedures in
force.
9.3 Controled treatment with fibrin sealant
- Each patient who might be included (see 7.1 and 7.2) 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. 9.4
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 him/herself; 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 (i.e.
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 21:00 h (day of surgery), at 8:00 h,
14:00 h and 21:00 h at day after surgery, at 8:00 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 10.1 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 Fisher's 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 (e.g. severe adverse events) the study will be
terminated early.
