Clinical trial NCT05391412: Effect of Prophylactic Fibrinogen Concentrate In Scoliosis Surgery
Official title: Effect of Prophylactic Fibrinogen Concentrate In Scoliosis Surgery: A Randomized Pilot Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Fibrinogen
Spine Deformity
Coagulopathy, Consumption
Bleeding
Keywords: fibrinogen
scoliosis
coagulopathy
Lead sponsor: Brno University Hospital
Sponsor class: OTHER
First posted: 2022-05-26
Enrollment: 32
Sex: ALL
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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. 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.

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.

Eligibility criteria: Inclusion Criteria:

Subjects will be eligible for the trial if they meet all of the following criteria:

1. Age \< 18 years of age at the time of enrolment
2. Elective scoliosis surgery
3. Signed the relevant informed consent form (more in Chapter 10.1)
4. Sexually active participants (≥ 15 years old) must agree to the use of following methods of contraception for the duration of this clinical trial:

   1. 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.
   2. Men - sexual abstinence or the use of an adequate contraceptive method (i.e. condom) in case of sexual intercourse.

Exclusion Criteria:

Subjects will not be eligible for the trial if they meet any of the following criteria:

1. Diagnosed congenital or acquired coagulopathy
2. Use of anticoagulants with the exception of perioperative prophylactic administration of Low molecular weight heparin (LMWH) to prevent venous thromboembolism (VTE)
3. Known hypersensitivity to the active substance or to any of the excipients of Investigational Medicinal Product (IMP)
4. History of deep vein thrombosis or pulmonary embolism
5. Pregnancy and lactation

Primary outcomes:
measure: Adverse event
timeFrame: through study completion, an average of 6 months
measure: Adverse drug reaction
timeFrame: through study completion, an average of 6 months
measure: Serious adverse event and reaction
timeFrame: through study completion, an average of 6 months
measure: Unexpected adverse reaction
timeFrame: through study completion, an average of 6 months
measure: Suspected unexpected serious adverse reaction
timeFrame: through study completion, an average of 6 months
Secondary outcomes:
measure: Deep-vein thrombosis
timeFrame: through study completion, an average of 6 months
measure: Pulmonary embolism
timeFrame: through study completion, an average of 6 months
measure: Infection or healing disorder
timeFrame: through study completion, an average of 6 months
measure: Length of stay
timeFrame: through study completion, an average of 6 months
measure: ICU length of stay
timeFrame: through study completion, an average of 6 months
measure: 28-day mortality
timeFrame: at day 28 of study
measure: Age
timeFrame: at the start of the study
measure: Sex
timeFrame: at the start of study
measure: Weight
timeFrame: at the start of study
measure: Haemoglobin
timeFrame: before surgery, immediately after surgery and 24 hours after surgery
measure: Haematocrit groups
timeFrame: before surgery, immediately after surgery and 24 hours after surgery
measure: Platelet count
timeFrame: before surgery, immediately after surgery and 24 hours after surgery
measure: Fibrinogen
timeFrame: before surgery, immediately after surgery and 24 hours after surgery
measure: Activated parcial thromboplastin time (aPTT)
timeFrame: before surgery, immediately after surgery and 24 hours after surgery
measure: Prothrombin time (PT)
timeFrame: before surgery, immediately after surgery and 24 hours after surgery
measure: Thrombin time (TT)
timeFrame: before surgery, immediately after surgery and 24 hours after surgery
measure: Total volume of blood loss
timeFrame: during surgery and within the 24-hour postoperative period
measure: Number of the surgical segments of the spine
timeFrame: immediately after surgery
measure: Volume of blood loss for the surgical segment of the spine
timeFrame: during surgery and within the 24-hour postoperative period
measure: Urinary output
timeFrame: within the 24-hour postoperative period
measure: Red blood cells (RBC) consumption - transfusion unit
timeFrame: during surgery and within the 24-hour postoperative period
measure: Red blood cells (RBC) consumption - volume
timeFrame: during surgery and within the 24-hour postoperative period
measure: Thrombocytes of apheresis (TAD) consumption - transfusion unit
timeFrame: during surgery and within the 24-hour postoperative period
measure: Thrombocytes of apheresis (TAD) consumption - volume
timeFrame: during surgery and within the 24-hour postoperative period
measure: Fresh frozen plasma (FFP) consumption - transfusion unit
timeFrame: during surgery and within the 24-hour postoperative period
measure: Fresh frozen plasma (FFP) consumption - volume
timeFrame: during surgery and within the 24-hour postoperative period
measure: Fibrinogen concentrate consumption
timeFrame: during surgery and within the 24-hour postoperative period
measure: Prothrombin complex concentrate (PCC) consumption
timeFrame: during surgery and within the 24-hour postoperative period
measure: Blood derivative corresponding to Fresh frozen plasma (Octaplas) consumption
timeFrame: during surgery and within the 24-hour postoperative period
measure: Crystalloid solutions consumption
timeFrame: during surgery and within the 24-hour postoperative period
measure: Colloid solutions consumption
timeFrame: during surgery and within the 24-hour postoperative period
measure: Number of patients receiving transfusion products
timeFrame: at hospital discharge
measure: Number of patients receiving blood derivatives
timeFrame: at hospital discharge
measure: Rate of recruitment of eligible patients who were approached for consent to participate
timeFrame: through study completion, an average of 6 months
measure: Percentage of missing outcome and clinical data
timeFrame: through study completion, an average of 6 months
Other outcomes:
Locations:
city: Brno
country: Czechia
facility: University Hospital Brno
Study officials:
affiliation: Masaryk University Brno and University Hospital
name: Roman Gal, M.D., PhD.
role: PRINCIPAL_INVESTIGATOR
References: