FibrinogenPhase 4EFISSNCT05391412
Effect of Prophylactic Fibrinogen Concentrate In Scoliosis Surgery
A Phase 4 study testing Fibrinogen Concentrate Human in people with Fibrinogen and Spine Deformity, run by Brno University Hospital at 1 site in Czechia.
Trial summary
EFISS is a prospective, randomized, placebo-controlled trial testing the feasibility, safety and efficacy of prophylactic administration of fibrinogen in paediatric spinal surgery. The study is monocentric and will be conducted in University Hospital Brno, Czech Republic. Read more about this study
- Who is it for?
- Ages Up to 18 years
- Conditions the study is for
- Fibrinogen, Spine Deformity, Coagulopathy, Consumption
- What is being tested?
- Fibrinogen Concentrate Human
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteCzechia
- Study dates
- 6 Jun 2022to 11 Jul 2023
- Phase
- Phase 4
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Subjects will be eligible for the trial if they meet all of the following criteria:
- Age < 18 years of age at the time of enrolment
- Elective scoliosis surgery
- Signed the relevant informed consent form (more in Chapter 10.1)
- Sexually active participants (≥ 15 years old) must agree to the use of following methods of contraception for the duration of this clinical trial:
- Women - proper use of a highly reliable method of contraception, i.e. combined hormonal contraception (oral, vaginal or transdermal form), gestagen hormonal contraceptives associated with ovulation inhibition (oral or injectable form) or sexual abstinence.
- Men - sexual abstinence or the use of an adequate contraceptive method (i.e. condom) in case of sexual intercourse.
Who cannot join
- Subjects will not be eligible for the trial if they meet any of the following criteria:
- Diagnosed congenital or acquired coagulopathy
- Use of anticoagulants with the exception of perioperative prophylactic administration of Low molecular weight heparin (LMWH) to prevent venous thromboembolism (VTE)
- Known hypersensitivity to the active substance or to any of the excipients of Investigational Medicinal Product (IMP)
- History of deep vein thrombosis or pulmonary embolism
- Pregnancy and lactation
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effect of Prophylactic Fibrinogen Concentrate In Scoliosis Surgery: A Randomized Pilot Study
EFISS is a prospective, randomized, placebo-controlled trial testing the feasibility, safety and efficacy of prophylactic administration of fibrinogen in paediatric spinal surgery. The study is monocentric and will be conducted in University Hospital Brno, Czech Republic. This is a pilot study in which the primary objective will be to evaluate the feasibility of a clinical trial in 32 selected patients undergoing scoliosis surgery. Participants will be randomized into study groups in a 1:1 allocation ratio and followed up for 28 days after surgery. The expected duration of this clinical trial is 8 months.
Read the detailed description
Scoliosis is an abnormal lateral curvature of the spine. It is most commonly diagnosed in childhood and early adolescence. Surgical treatment is indicated for severe scoliosis to reduce back pain, neurological symptoms and prevent deterioration of respiratory and cardiovascular function. Scoliosis surgery is often accompanied by a large blood loss and blood transfusion is necessary in 30% to 60% of operated patients. The limited availability, high cost and risk of complications associated with the administration of transfusion products has led to efforts to introduce procedures that aim to reduce the magnitude of blood loss during surgery. Fibrinogen plays an important role in coagulum formation and bleeding arrest. Insufficient fibrinogen levels lead to impaired blood clotting and increased bleeding during major surgery. It has also been shown that patients with higher preoperative fibrinogen levels have less perioperative blood loss. Prophylactic administration of fibrinogen leads to a reduction in blood loss and the number of transfusions administered in some types of procedures. Prophylactic administration of fibrinogen at a dose of 30 mg/kg has been shown to be safe even in paediatric patients. Whether prophylactic fibrinogen administration before scoliosis surgery has an effect on the magnitude of blood loss is unclear. To plan a sufficiently large randomized trial to clarify the effect of prophylactic fibrinogen administration before elective scoliosis surgery on the magnitude of blood loss, and the need for transfusion administration, our team of investigators decided to organize this pilot study.
Prophylactic administration of fibrinogen has been widely described in various indications in recent decades. Among others, it is mainly cardiovascular surgery, where some authors refer the absence of the effect of fibrinogen administration on postoperative bleeding and some even the association with increased allogeneic blood product transfusion. On the contrary, one-hundred sixteen patients undergoing heart surgery with an expected cardiopulmonary bypass were part of the placebo-controlled double-blind study in which fibrinogen concentrate significantly reduced postoperative bleeding with a significant reduction in allogeneic blood products transfusions. Reduction of bleeding after coronary artery bypass graft without signs of postoperative hypercoagulability associated with preoperative infusion of fibrinogen concentrate is descibed. Fibrinogen administration has also been tested in double-blind placebo-controlled clinical trials associated with urologic surgery and gynaecological surgery procedures. Regarding skeletal surgery, the effect of prophylactically administered fibrinogen on postoperative bleeding has also been studied. Intraoperative administration of fibrinogen was successfully used to significantly decrease bleeding and transfusions in 30 children aged 6 months to 17 years undergoing craniosynostosis surgery.
Compared to these results, no differences in blood loss and transfusion requirements were found between treated and placebo groups in younger paediatric patients up to 25 months during craniofacial surgery. Clinical trials directly related to spinal surgery have also been described. This clinical study was performed in 30 adult patients undergoing lumbar surgery, in which 1g of fibrinogen dissolved in distilled water was injected near the surgical incision in the intervention group (n=15). Bleeding during and after surgery in the control group was significantly higher than in the intervention group (P<0.05), and therefore the efficacy of fibrinogen was demonstrated in this indication. Efficacy and safety of preoperatively administrated fibrinogen concentrate (30 mg / kg to 2 g maximum) have also been confirmed in the paediatric population. A total of 102 children (12 - 18 years) with idiopathic scoliosis undergoing surgery were randomized to test and control groups (n=51), where fibrinogen infusion reduced median perioperative bleeding by approximately 155 ml compared to placebo. Fibrinogen administrated in the test group in this case did not reduce the amount of allogeneic blood product transfusion.
The clinical outcome of an individual participant in the prophylactic administration of fibrinogen prior to scoliosis surgery may or may not be improved. If effective, this administration will reduce blood loss during surgery and reduce the need for blood transfusions. In any case, participation in this study will improve knowledge about the prophylactic use of fibrinogen during scoliosis surgery, and all participants in this study will contribute to this socially beneficial knowledge. The same surgical procedure will be used in both study groups as is standard in the surgical treatment of spinal scoliosis. The method is generally well tolerated by patients and does not pose significant risks. The potential risks of participating in the EFISS study may include the rare development of adverse reactions, including fever, allergic and anaphylactic reactions, or thromboembolic events associated with the administration of investigational medicinal product.
- Conditions
- Fibrinogen, Spine Deformity, Coagulopathy, Consumption, Bleeding
- Being tested
- Fibrinogen Concentrate Human
- Keywords
- fibrinogen, scoliosis, coagulopathy
- Medical subject headings
- Disseminated Intravascular Coagulation, Hemorrhage, Scoliosis, Hemostatic Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fibrinogen Concentrate HumanDrug
Also called HAEMOCOMPLETTAN P
Patients in the intervention group will receive single administration of fibrinogen concentrate intravenously at a dose of 20-30 mg/kg (depending on body weight and clinical condition, according to SmPC). The medicinal product will be diluted in a 100 ml infusion bag and administered after induction of anaesthesia prior beginning of surgery. The infusion rate should not exceed approximately 5 ml per minute.
| Study group | Role | What they receive |
|---|---|---|
| Fibrinogen group | Experimental | The fibrinogen concentrate (20-30mg/kg, max 2g) will be administered in 100ml (Aqua pro injection) intravenously to the patient. Receives: Drug: Fibrinogen Concentrate Human |
| Control group | No intervention | Patients in the control group will not receive any additional medication than standard of care. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse event
The following primary endpoint will be monitored to evaluate the primary objective:
Adverse event - Any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment.
Measured: through study completion, an average of 6 months
Adverse drug reaction
The following primary endpoint will be monitored to evaluate the primary objective:
Adverse drug reaction - All untoward and unintended responses to an investigational medicinal product related to any dose administered
Measured: through study completion, an average of 6 months
Serious adverse event and reaction
The following primary endpoint will be monitored to evaluate the primary objective:
Serious adverse event and reaction - A serious adverse event/reaction is any untoward medical occurrence or effect that at any dose:
- Results in death;
- Is life-threatening;
- Requires hospitalization or extension of existing hospitalization;
- Results in persistent or significant disability or incapacity;
- Is a congenital anomaly or birth defect
Measured: through study completion, an average of 6 months
Unexpected adverse reaction
The following primary endpoint will be monitored to evaluate the primary objective:
Unexpected adverse reaction - Adverse reaction, the nature, severity, or outcome of which
Measured: through study completion, an average of 6 months
Suspected unexpected serious adverse reaction
The following primary endpoint will be monitored to evaluate the primary objective:
Suspected unexpected serious adverse reaction - Any suspected adverse reaction related to the study treatment that is both serious and unexpected.
Measured: through study completion, an average of 6 months
Secondary outcomes (35)
Deep-vein thrombosis
Incidence of adverse events and reactions according to following Adverse Events of Special Interest (AESI)
▪ Deep-vein thrombosis verified on duplex ultrasound imaging (YES/NO)
Measured: through study completion, an average of 6 months
Pulmonary embolism
Incidence of adverse events and reactions according to following Adverse Events of Special Interest (AESI)
▪ Pulmonary embolism confirmed on CT (YES/NO)
Measured: through study completion, an average of 6 months
Infection or healing disorder
Incidence of adverse events and reactions according to following Adverse Events of Special Interest (AESI)
▪ Infection or healing disorder requiring re-surgery and / or initiation of antibiotic therapy (YES/NO)
Measured: through study completion, an average of 6 months
Length of stay
▪ Length of stay (LOS) - day of admission - day of discharge will be counted as 1 day
Measured: through study completion, an average of 6 months
ICU length of stay
▪ ICU length of stay (ICU LOS) - day of admission - day of discharge will be counted as 1 day
Measured: through study completion, an average of 6 months
28-day mortality
▪ 28-day mortality (number of patients who are not alive 28 days after randomization)
Measured: at day 28 of study
Age
Comparison of demographic characteristics between study groups
▪ Age (years)
Measured: at the start of the study
Sex
Comparison of demographic characteristics between study groups
▪ Sex (male, female)
Measured: at the start of study
Weight
Comparison of demographic characteristics between study groups
▪ Weight (kilograms)
Measured: at the start of study
Haemoglobin
Comparison of laboratory values of selected haematological parameters between study groups
▪ Haemoglobin (g/l; before, at the end of surgery and 24 hours after surgery)
Measured: before surgery, immediately after surgery and 24 hours after surgery
Haematocrit groups
Comparison of laboratory values of selected haematological parameters between study
▪ Haematocrit (%; before, at the end of surgery and 24 hours after surgery)
Measured: before surgery, immediately after surgery and 24 hours after surgery
Platelet count
Comparison of laboratory values of selected haematological parameters between study groups
▪ Platelet count (n/l; before, at the end of surgery and 24 hours after surgery)
Measured: before surgery, immediately after surgery and 24 hours after surgery
Fibrinogen
Comparison of laboratory values of selected haematological parameters between study groups
▪ Fibrinogen (g/l; before, at the end of surgery and 24 hours after surgery)
Measured: before surgery, immediately after surgery and 24 hours after surgery
Activated parcial thromboplastin time (aPTT)
Comparison of laboratory values of selected haematological parameters between study groups
▪ aPTT (s; before, at the end of surgery and 24 hours after surgery)
Measured: before surgery, immediately after surgery and 24 hours after surgery
Prothrombin time (PT)
Comparison of laboratory values of selected haematological parameters between study groups
▪ PT (s; before, at the end of surgery and 24 hours after surgery)
Measured: before surgery, immediately after surgery and 24 hours after surgery
Thrombin time (TT)
Comparison of laboratory values of selected haematological parameters between study groups
▪ TT (s; before, at the end of surgery and 24 hours after surgery)
Measured: before surgery, immediately after surgery and 24 hours after surgery
Total volume of blood loss
Comparison of blood loss level and its compensation between study groups
▪ Total volume of blood loss (ml; during surgery and in the 24-hour postoperative period)
Measured: during surgery and within the 24-hour postoperative period
Number of the surgical segments of the spine
Comparison of blood loss level and its compensation between study groups
▪ Number of the surgical segments of the spine (n; postoperatively)
Measured: immediately after surgery
Volume of blood loss for the surgical segment of the spine
Comparison of blood loss level and its compensation between study groups
▪ Volume of blood loss for the surgical segment of the spine (ml; during surgery and in the 24-hour postoperative period)
Measured: during surgery and within the 24-hour postoperative period
Urinary output
Comparison of blood loss level and its compensation between study groups
▪ Urinary output (ml; in the 24-hour postoperative period)
Measured: within the 24-hour postoperative period
Red blood cells (RBC) consumption - transfusion unit
Comparison of blood loss level and its compensation between study groups
▪ Red blood cells (RBC) consumption (transfusion units consumption during surgery and in the 24-hour postoperative period)
Measured: during surgery and within the 24-hour postoperative period
Red blood cells (RBC) consumption - volume
Comparison of blood loss level and its compensation between study groups
▪ Red blood cells (RBC) consumption (total volume of infusion during surgery and in the 24-hour postoperative period)
Measured: during surgery and within the 24-hour postoperative period
Thrombocytes of apheresis (TAD) consumption - transfusion unit
Comparison of blood loss level and its compensation between study groups
▪ Thrombocytes of apheresis (TAD) consumption (transfusion units consumption during surgery and in the 24-hour postoperative period)
Measured: during surgery and within the 24-hour postoperative period
Thrombocytes of apheresis (TAD) consumption - volume
Comparison of blood loss level and its compensation between study groups
▪ Thrombocytes of apheresis (TAD) consumption (total volume of infusion during surgery and in the 24-hour postoperative period)
Measured: during surgery and within the 24-hour postoperative period
Fresh frozen plasma (FFP) consumption - transfusion unit
Comparison of blood loss level and its compensation between study groups
▪ Fresh frozen plasma (FFP) consumption (transfusion units consumption during surgery and in the 24-hour postoperative period)
Measured: during surgery and within the 24-hour postoperative period
Fresh frozen plasma (FFP) consumption - volume
Comparison of blood loss level and its compensation between study groups
▪ TFresh frozen plasma (FFP) consumption (total volume of infusion during surgery and in the 24-hour postoperative period)
Measured: during surgery and within the 24-hour postoperative period
Fibrinogen concentrate consumption
Comparison of blood loss level and its compensation between study groups
▪ Fibrinogen concentrate consumption (consumption in grams during surgery and in the 24-hour postoperative period)
Measured: during surgery and within the 24-hour postoperative period
Prothrombin complex concentrate (PCC) consumption
Comparison of blood loss level and its compensation between study groups
▪ Prothrombin complex concentrate (PCC) consumption (consumption in units during surgery and in the 24-hour postoperative period)
Measured: during surgery and within the 24-hour postoperative period
Blood derivative corresponding to Fresh frozen plasma (Octaplas) consumption
Comparison of blood loss level and its compensation between study groups
▪ Blood derivative corresponding to Fresh frozen plasma (Octaplas) consumption (consumption in units during surgery and in the 24-hour postoperative period)
Measured: during surgery and within the 24-hour postoperative period
Crystalloid solutions consumption
Comparison of blood loss level and its compensation between study groups
▪ Crystalloid solutions consumption (total volume of infusion during surgery and in the 24-hour postoperative period)
Measured: during surgery and within the 24-hour postoperative period
Colloid solutions consumption
Comparison of blood loss level and its compensation between study groups
▪ Colloid solutions consumption (total volume of infusion during surgery and in the 24-hour postoperative period)
Measured: during surgery and within the 24-hour postoperative period
Number of patients receiving transfusion products
Comparison of blood loss level and its compensation between study groups
▪ Number of patients receiving transfusion products
Measured: at hospital discharge
Number of patients receiving blood derivatives
Comparison of blood loss level and its compensation between study groups
▪ Number of patients receiving blood derivatives
Measured: at hospital discharge
Rate of recruitment of eligible patients who were approached for consent to participate
Feasibility assessment
▪ Rate of recruitment of eligible patients who were approached for consent to participate (%; feasibility criterion >75% enrolled participants)
Measured: through study completion, an average of 6 months
Percentage of missing outcome and clinical data
Feasibility assessment
▪ Percentage of missing outcome and clinical data (< 10% missing outcome data including ICU and hospital length of stay (LOS) and survival; < 10% missing clinical data obtained from clinical medical notes and electronic patient records)
Measured: through study completion, an average of 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 May 2022
- Study start6 Jun 2022
- Primary completion11 Jul 2023
- Study completion11 Jul 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for FibrinogenStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brno University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ondrej Hrdy, Brno University Hospital
- Investigators
- Roman Gal, M.D., PhD., Principal investigator, Masaryk University Brno and University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05391412
- Sponsor's protocol ID
- CT0012022
- Acronym
- EFISS
- Status last verified
- Oct 2026
- First submitted
- 2 May 2022
- Last updated
- 16 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Hudec J, Vrbica K, Hrdy O, Galko M, Repko M, Stepanova R, Demlova R, Kubelova M, Gal R. Effect of prophylactic fibrinogen concentrate in scoliosis surgery (EFISS): a randomised pilot trial. BMJ Open. 2025 Oct 7;15(10):e100137. doi: 10.1136/bmjopen-2025-100137.
PubMed 41062134Vrbica K, Hudec J, Hrdy O, Galko M, Horalkova H, Demlova R, Kubelova M, Repko M, Gal R. Effect of Prophylactic Fibrinogen Concentrate In Scoliosis Surgery (EFISS): a study protocol of two-arm, randomised trial. BMJ Open. 2023 May 26;13(5):e071547. doi: 10.1136/bmjopen-2022-071547.
PubMed 37236666