What is the comparative efficacy of fibrin sealants in general? Is there any data comparing these agents specifically in neurosurgical surgical procedures?

Comment by InpharmD Researcher

General and neurosurgical-specific direct comparative data regarding the selected fibrin sealants (Tachosil®, Tisseel®, Vistaseal®) are limited. Based on the results of a 2020 meta-analysis, Vistaseal was more successful in achieving hemostasis at 4 and 10 minutes after application at a clotting time of 2 minutes compared to Tisseel. However, this was limited to peripheral vascular surgeries. Available data for fibrin sealants are focused on studies comparing individual fibrin sealants to standard hemostatic techniques or other fibrin sealants such as Surgicel®.

Background

A 2020 meta-analysis compared the efficacy and safety of fibrin sealants for achieving hemostasis in peripheral vascular surgery at clotting times of 1 minute (1C) and 2 minutes (2C). A total of 5 trials (N= 693) were included for analysis. Compared to manual compression, significant improvements in hemostasis by 4 minutes after treatment application was found with Vistaseal 2C (relative risk [RR] 2.67, 95% credible interval [CrI] 2.13 to 3.34), Vistaseal 1C (RR 2.00, 95% CrI 1.45 to 2.65), and Tisseel 2C (RR 1.99, 95% CrI 1.48 to 2.60). Tisseel 1C was not found to be significantly different in achieving hemostasis 4 minutes after application (RR 1.40, 95% CrI 0.70 to 2.33). Among fibrin sealants, Vistaseal 2C was associated with a significantly higher probability of achieving hemostasis at 4 minutes after application than Vistaseal 1C (RR 1.33, 95% CrI 1.02 to 1.82), Tisseel 2C (RR 1.34, 95% CrI 1.05 to 1.77), and Tisseel 1C (RR 1.90, 95% CrI 1.18 to 3.74). For achieving hemostasis by 10 minutes, Evicel 1C and Vistaseal 2C had the highest probabilities. Similar to the primary analysis, all fibrin sealants, except Tisseel 1C, significantly improved the probability of achieving hemostasis at 10 minutes after application compared with manual compression. Vistaseal 2C was associated with a significantly higher probability of achieving hemostasis at 10 minutes after application than Tisseel 2C (RR 1.16, 95% CrI 1.02 to 1.35) and Tisseel 1C (RR 1.23, 95% CrI 1.01 to 1.76). This network meta-analysis is limited by the lack of direct comparative evidence included. [1]

A 2018 review reported on the use of TachoSil® fibrin sealant patch as dural sealant in patients undergoing spinal intradural tumor surgery. Data were reported on 35 patients (age 58.14 ± 15.56 years, follow-up 23.20 ± 9.76 months). Functional status was assessed preoperatively and at latest follow-up using Modified McCormick Scale (MMS). The spinal segments operated on included cervical (3 cases, 8.57%), thoracic (13, 37.14%), lumbar (14, 40%), cervico-thoracic (2, 5.71%), and thoraco-lumbar (3, 8.57%). Preoperatively, 18 patients (51.42%) were classified as MMS grade I or II and 17 (48.57%) were grade III, IV, or V. At follow-up, an improvement in MMS was observed in 23 patients (65.71%) and a stable functional status in 12 patients (34.28%). No product-related adverse reactions were observed. The authors concluded TachoSil® after dural closure is safe and effective for intradural spinal tumors. [2]

A 2017 review aimed to summarize the current efficacy and safety literature of fibrin sealants in dura sealing and the prevention/treatment of cerebrospinal fluid leaks. A total of 33 articles from 32 studies (N= 2,935) enrolling patients who were exposed to fibrin sealant were included; 3 were randomized controlled trials (RCTs) and the remaining were prospective cohort analyses, case controlled studies, and prospective or retrospective case series. One randomized controlled trial (N= 89) found a greater rate of intraoperative watertight dura closure in the fibrin sealant group compared to the control group (92.1% vs. 38%; p <0.001); however, post-operative cerebrospinal fluid leakage occurred more often in the fibrin sealant group than the control group (6.7% vs. 2%; p > 0.05), but this was not significant. The other two RCTs included in this review were of low evidence that were not powered to demonstrate a significant advantage of fibrin sealant. The first of these RCTs (N= 62) found 78% of patients to have postoperative CSF leaks in the fibrin sealant group compared to 74% of patients in the standard of care alone (dura mater closed with sutures and patches) group. The second RCT did not observe any CSF leakage postoperatively in any study patients; no adverse events or complications were reported. The authors concluded that evidence from a single RCT indicates fibrin sealants provided a higher rate of intraoperative watertight closure of the dura suture line than control; however, there is a need for more well-designed prospective observational trials assessing the safety and efficacy of fibrin sealants. [3]

A 2019 meta-analysis by Kinaci et al. investigated the efficacy of sealants in preventing postoperative CSF leakage in spine surgery. Among 2,542 included cases of intended or unintended durotomy, sealant was applied in 2,193 cases (86.3%), whereas 349 cases (13.7%) underwent suture repair only. Fibrin glue sealants were the most common type of sealant used (1,696 cases [66.8%]) in combination with a graft or alone. Based on 4 comparative studies with 540 sealed cases and 343 cases with primary suture closure only, the quantity of CSF leakage did not differ between the sealant group (50/540 [9.1%]) and the suture-only group (48/343 [13.8%]) (risk ratio [RR], 0.58; 95% confidence interval [CI], 0.18 to 1.82). Moreover, the infection rate did not differ between the sealant and primary suture groups as well (RR, 0.94; 95% CI, 0.55 to 1.61). The secondary analysis of all cases showed regardless of sealant use, endoscopic or minimally invasive surgery had lower CSF leakage rates than the open surgery (RR, 0.18; 95% CI, 0.05 to 0.75). This analysis found no difference in the rate of CSF leakage after spinal surgery with fibrin sealant use; however, the rate of CSF leakage was significantly lower in open surgery regardless of sealant usage. Fibrin sealants are not approved for dural sealings, and this analysis found that extra treatment with fibrin glue does not lead to less postoperative CSF leakage than sutures in spinal surgeries. [4]

A 1999 review describes the effective use of fibrin sealant to fix CSF leakages after trauma or surgery in case series. Successful and permanent sealing was seen in all 57 patients who underwent repair of CSF leakage with pedunculated periosteal flaps with fibrin sealant compared to a 42.3% leakage rate in patients who underwent repair with lyophilised dura and cyanoacrylate adhesive. Fibrin sealant usage was also associated with a reduction in length of hospital stay (16.3 vs 27 days). Another case series reported CSF leakage persisted in only 2/15 (13.3%) patients with intraoperative leakage during repair of the septal bone with fibrin sealant on the sellar floor and anterior wall of the sphenoid sinus during transsphenoidal surgery. No leakage was reported over a 12 month period in any of the 104 patients who did not report intraoperative leakage. [5]

References:

[1] Danker Iii W, DeAnglis A, Ferko N, Garcia D, Hogan A. Comparison of fibrin sealants in peripheral vascular surgery: A systematic review and network meta-analysis. Ann Med Surg (Lond). 2020;61:161-168. Published 2020 Dec 9. doi:10.1016/j.amsu.2020.12.003
[2] Montano N, Pignotti F, Auricchio AM, et al. Results of TachoSil® associated with fibrin glue as dural sealant in a series of patients with spinal intradural tumors surgery. Technical note with a review of the literature. J Clin Neurosci. 2019;61:88-92. doi:10.1016/j.jocn.2018.10.138
[3] Esposito F, Angileri FF, Kruse P, et al. Fibrin Sealants in Dura Sealing: A Systematic Literature Review [published correction appears in PLoS One. 2017 Apr 6;12 (4):e0175619]. PLoS One. 2016;11(4):e0151533. Published 2016 Apr 27. doi:10.1371/journal.pone.0151533
[4] Kinaci A, Moayeri N, van der Zwan A, et al. Effectiveness of sealants in prevention of cerebrospinal fluid leakage after spine surgery: a systematic review. World Neurosurg. 2019;127:567-575.e1. doi:10.1016/j.wneu.2019.02.236
[5] Dunn CJ, Goa KL. Fibrin sealant: a review of its use in surgery and endoscopy. Drugs. 1999;58(5):863-886. doi:10.2165/00003495-199958050-00010

Literature Review

A search of the published medical literature revealed 4 studies investigating the researchable question:

What is the comparative efficacy of fibrin sealants in general? Is there any data comparing these agents specifically in neurosurgical surgical procedures?

Level of evidence

C - Multiple studies with limitations or conflicting results  Read more→



Please see Tables 1-4 for your response.


 

Tisseel® versus Hemopatch® for dural sealing in neurosurgery. A prospective study in a tertiary center

Design

Prospective observational study

N= 147

Objective

To evaluate the incidence of pseudomeningocele and cerebrospinal fluid (CSF) leak in cranial and spinal neurologic procedures with the use of Tisseel and Hemopatch

Study Groups

Tisseel (n= 65)

Hemopatch (n= 82)

Inclusion Criteria

Adult patients without a previous CSF leak undergoing intradural cranial or spinal procedures and had dura closed with a fibrin sealant at a select tertiary care center in Spain

Exclusion Criteria

Patients undergoing endoscopic procedures

Methods

This observational study did not incorporate any randomization. One sealant is used in each surgical procedure as needed, interchangeably, at the discretion of the operating surgeon. Sealants were utilized in patients considered to be at risk for CSF leak (spinal, infratentorial or open cranial base) or if a dural defect was observed. Patients were unaware of sealant selection. 

Duration

Patients underwent procedure between September 2017 to December 2018

Follow-up: 6 months from surgery

Outcome Measures

Primary: incidence of pseudomeningocele and CSF leak

Secondary: incidence of surgical-site infection, epidural hematoma, and the influence of a previous surgery

Baseline Characteristics

 

All patients (N= 147)

 

 

Age, years (range)

56.8 (17 to 86)    

Female

89 (60.5%)    

Arterial hypertension

53 (36.1%)    

Diabetes mellitus

28 (19%)    

Smokers

46 (31%)    

Type of procedure

Supratentorial craniotomy

Infratentorial craniotomy

Spinal intradural lesion

 

97 (66%)

32 (21.8%)

18 (12.2%)

   

Results

Endpoint

Tisseel (n= 65)

Hemopatch (n= 82)

p-value 

Pseudomeningocele

14 (21.5%) 8 (9.75%) 0.062 (95% CI 0.99 to 6.54)

CSF leak

9 (13.8%) 3 (3.6%) <0.05 (OR 4.23, 95% CI 1.09 to 16.39)

Surgical site infection

A statistically significant relationship was found for patients having an infection and the incidence of a CSF leak (p< 0.05; OR 5.71, 95% CI 1.610 to 20.286).

Epidural hematoma

No relation was found in incidence of CSF leak in relation to an epidural hematoma (p= 0.696). 

Influence of previous surgery

A statistically significant relationship was found for patients having a previous intervention and the incidence of a CSF leak (p< 0.05; OR 5.71, 95% CI 1.610 to 20.286). 

OR, odds ratio; CI, confidence interval

Adverse Events

None reported. 

Study Author Conclusions

The incidence of pseudomeningocele and CSF leak was higher with the use of Tissel, although its relation was significant only for CSF leak. The procedure done and use of dural plasty were not confusion factors in multivariate analysis. There was no higher incidence of complications with the use of fibrin sealants. The authors conclude that the use of sealants is safe and Hemopatch is more effective than Tisseel to reduce the incidence of CSF fistula. However, it is recommended to plan randomized controlled trials with larger samples to get stronger evidence.

InpharmD Researcher Critique

This study incorporated a small, non-randomized sample of patients. Additionally, this appears to be a single-center study conducted in Spain, and standard of care and clinical practices may vary compared to that of the United States. 



References:

Diaz-Molina J, Martínez R, González-Vargas P, Calero L, Azevedo A, Conde C. Tisseel® versus Hemopatch® for dural sealing in neurosurgery. A prospective study in a tertiary center. Neurochirurgie. 2020;66(6):429-434. doi:10.1016/j.neuchi.2020.09.008

 

Fibrin Sealant Patch (TachoSil) vs Oxidized Regenerated Cellulose Patch (Surgicel Original) for the Secondary Treatment of Local Bleeding in Patients Undergoing Hepatic Resection: A Randomized Controlled Trial

Design

Multicenter, randomized, open-label study

N= 224

Objective

To compare fibrin sealant patch (FSP; TachoSil; Takeda Pharma A/S) with oxidized regenerated cellulose gauze (ORCG; Surgicel Original; Ethicon) for the secondary treatment of local bleeding after hepatic resection in adult and pediatric patients

Study Groups

TachoSil (n= 114)

Surgicel (n= 110)

Inclusion Criteria

Pediatric (newborn to 16 years) and adult (≥ 17 years) patients with elective resection of at least the equivalent tissue volume of one anatomical segment of the liver if minor to moderate bleeding from resection area persisted after primary control of arterial or venous bleeding using standard techniques

Exclusion Criteria

Emergency surgery, known or suspected hypersensitivity to any component of either study treatment, current alcohol or drug abuse, or unwillingness to receive blood products

Methods

Patients were randomized (1:1) after completion of primary hemostatic treatment. Blinding was not possible due to differences in product appearance. Treatment was applied under aseptic conditions; the number of patches used varied based on size of bleeding site. Patches were applied with light pressure against the wound area for 3 minutes. If hemostatsis was not achieved after 3 minutes, pressure was reapplied and hemostasis was assessed again at 5 minutes. If needed at this time, a second application of trial treatment was performed. If hemostasis was not obtained after 10 minutes from the first application, any hemostatic rescue treatment could be applied, except TachoSil, Surgicel, or products containing thrombin or fibrinogen of any origin. Treatment failure was defined as visible bleeding after 10 minutes. 

Duration

6 months

Outcome Measures

Primary: proportion of adult patients with intraoperative hemostasis (no visible bleeding) at target area within 3 minutes of application of first treatment

Secondary: intraoperative hemostasis within 5 minutes of application of first treatment and time to intraoperative hemostasis at the target area within 10 minutes

Baseline Characteristics

  TachoSil (n= 114)

Surgicel (n= 110)

 

Age, years

58.4 ± 13.7 57.8 ± 14.3  

Female

47.4% 46.4%  

Body mass index (BMI), kg/m2

28.1 ± 5.5 27.2 ± 5.7  

Surgical indication

Malignancy

Benign lesions

Organ donation

Other

 

86 (75.4%)

10 (8.8%)

11 (9.6%)

7 (6.1%)

 

87 (79.8%)

9 (8.3%)

9 (8.3%)

4 (3.6%)

 

Concomitant medications

Antihemorrhagic agents

Antithrombotic agents

 

24 (21.1%)

95 (83.3%)

 

27 (24.8%)

87 (79.8%)

 

Results

Endpoint

TachoSil (n= 114)

Surgicel (n= 110)

Odds ratio (95% confidence interval [CI]; p-Value)

Hemostasis within 3 minutes

92 (80.7%)

55 (50.0%)

4.87 (2.55 to 9.29; p< 0.001)

Hemostasis within 5 minutes

108 (94.7%)

84 (76.4%)

6.24 (2.39 to 16.30; p< 0.001)

Hemostasis within 10 minutes

Required rescue hemostasis

114 (100%)

0

99 (89.8%)

12 (10.9%)

--

Hemostasis at 3 minutes in pediatric patients

17/20 (85.0%)

4/9 (44.4%)

--

Adverse Events

Total number of treatment-emergent adverse events (TEAEs) were similar between the TachoSil and Surgicel groups (93.9% vs 93.6%). The majority were of mild to moderate in severity. 

TEAEs related to treatment were determined in 5 (4.4%) of the TachoSil group versus 4 (3.7%) of the Surgicel group. Three of the related TEAEs were considered serious in the TachoSil group (infectious peritonitis, liver abscess, and postoperative adhesion) and two in the Surgicel group (intra-abdominal fluid collection and peritoneal abscess).

Study Author Conclusions

The FSP (TachoSil) was safe and superior to ORCG (Surgicel Original) for achieving hemostasis in patients undergoing hepatic resection.

InpharmD Researcher Critique

Pediatric patients represent only a fraction of the population. The majority of indications were related to malignancy. 



References:

Genyk Y, Kato T, Pomposelli JJ, et al. Fibrin Sealant Patch (TachoSil) vs Oxidized Regenerated Cellulose Patch (Surgicel Original) for the Secondary Treatment of Local Bleeding in Patients Undergoing Hepatic Resection: A Randomized Controlled Trial. J Am Coll Surg. 2016;222(3):261-268. doi:10.1016/j.jamcollsurg.2015.12.007

 

A Prospective, Randomized, Phase III Study to Evaluate the Efficacy and Safety of Fibrin Sealant Grifols as an Adjunct to Hemostasis as Compared to Cellulose Sheets in Hepatic Surgery Resections

Design

Prospective, phase III, randomized controlled trial

N= 325

Objective

To compare the efficacy and safety of Fibrin Sealant Grifols (FS Grifols) with oxidized cellulose sheets (Surgicel®) as adjuncts to hemostasis during hepatic resections

Study Groups

FS Grifols group (n= 163)

Surgicel® group (n= 162)

Inclusion Criteria

Both adult and pediatric patients; hemoglobin levels ≥ 8.0 g/dL at baseline, open elective resection of at least one anatomical hepatic segment, or equivalent tissue with an identifiable target bleeding site (TBS)

Exclusion Criteria

Traumatic injury or infective process in the anatomic surgical area, an organ transplant during the same surgical procedure, history of severe reactions to any blood-derived product, FS Grifols- or Surgicel®-reported sensitivity, and pregnancy

Methods

The clinical trial was conducted in two parts, both having a 1:1 randomization into FS Grifols or Surgicel® treatment: (1) the preliminary part to familiarize investigators with the use of study treatments and (2) the primary part where both efficacy and safety data were collected.

Once primary hemostatic measures were taken, the patient was considered eligible for enrollment and randomized to treatment with either FS Grifols or Surgicel®. FS Grifols was applied onto the TBS surface by spraying (10 cm distance with a 1–1.75 bar pressure) in short bursts (0.1–0.2 ml). The maximum total volume of FS Grifols allowed was 12 mL (2 FS Grifols kits). Four 4″ × 8″ Surgicel® original absorbable hemostat sheets were allotted for each surgical procedure. 

Duration

Follow-up: 3 months

Outcome Measures

Primary: proportion of patients achieving hemostasis at target bleeding sites (TBS) within 4 min (T4) of treatment application

Secondary: time to hemostasis (TTH) at a later time point if re-bleeding occurs, cumulative proportion of patients achieving hemostasis by time points T2, T3, T5, T7, and T10

Baseline Characteristics

Characteristics

Preliminary + Primary part*

p-Value

FS Grifols (n= 163)

Surgicel® (n=162)

Age

58.8 ± 13.8 57.0 ± 15.2 --

Weight, kg

77.3 ± 17.3 78.3 ± 17.7 --

Male

85 (52.1%) 85 (52.5%) --

Medical history

Hypertension

Gastroesophageal reflux disease

Drug hypersensitivity

Metastases to liver

Hepatocellular cardinoma

Type 2 diabetes mellitus

Coronary artery disease

Hyperlipidemia

Cirrhosis

 

100 (61.3%)

31 (19.0%)

31 (19.0%)

28 (17.2%)

20 (12.3%)

15 (9.2%)

10 (6.1%)

19 (11.7%)

9 (5.5%)

 

90 (55.6%)

18 (11.1%)

32 (19.8%)

35 (21.6%)

22 (13.6%)

18 (11.1%)

5 (3.1%)

17 (10.5%)

5 (3.1%)

--

TBS size

Small (≤ 10 cm2 )

Medium (> 10 and ≤ 100 cm2)

Large (> 100 cm2)

 

27 (16.6%)

125 (76.7%)

11 (6.7%)

 

36 (22.2%)

118 (72.8%)

8 (4.9%)

--

*Preliminary consisted of FS Grifols (n= 52), Surgicel® (N= 49); Primary consisted of FS Grifols (n= 111), Surgicel® (n= 113); demographic and baseline characteristics of patients included in the study were generally similar between the two treatment groups across both parts of the study.

Results

Endpoint

Preliminary + Primary part

p-Value

FS Grifols (n= 163)  Surgicel® (n=162)

Rate of hemostasis at the TBS by T4 

92.8% 80.5% 0.01

TTH, min

2.8 ± 0.14 3.8 ± 0.24 < 0.001

The rate of hemostasis by T2, T5, and T7 was higher and statistically superior in the FS Grifols group compared to Surgicel®. No substantial differences in adverse events (AE) were noted between treatment groups. The most common AEs were procedural pain (36.2 vs. 37.7%), nausea (20.9 vs. 23.5%), and hypotension (14.1 vs 6.2%).

Adverse Events

Common Adverse Events: procedural pain (36.2% FS Grifols vs. 37.7% Surgicel®), nausea (20.9% vs. 23.5%), and hypotension (14.1% vs. 6.2%)

Serious Adverse Events: 4 (2.5% vs. 0%)

Percentage that Discontinued due to Adverse Events: 0 vs. 0

Study Author Conclusions

FS Grifols was safe and well tolerated as a local hemostatic agent during liver resection surgeries. Overall, data demonstrate that the hemostatic efficacy of FS Grifols is superior to Surgicel® and support the use of FS Grifols as an effective local hemostatic agent in these surgical procedures.

InpharmD Researcher Critique

This is a multicenter, international clinical trial carried out in 33 study centers located in the US, Europe, and Russia encompassing a wider range of population groups. Participants and investigators were non-blinded due to fundamentally different treatment modalities which may have introduced bias in the interpretation of specific data points.



References:

Bjelović M, Ayguasanosa J, Kim RD, et al. A Prospective, Randomized, Phase III Study to Evaluate the Efficacy and Safety of Fibrin Sealant Grifols as an Adjunct to Hemostasis as Compared to Cellulose Sheets in Hepatic Surgery Resections. J Gastrointest Surg. 2018;22(11):1939-1949. doi:10.1007/s11605-018-3852-4

 

A Prospective, Single-Blind, Randomized, Phase III Study to Evaluate the Safety and Efficacy of Fibrin Sealant Grifols as an Adjunct to Hemostasis During Soft Tissue Open Surgery

Design

Phase III, single-blind, randomized, prospective, controlled, multicenter clinical trial

N= 224

Objective

To evaluate the safety and hemostatic effectiveness of a human plasma-derived fibrin sealant (FS Grifols) in soft tissue open surgery

Study Groups

FS Grifols (n= 116)

Surgicel® (n= 108)

Inclusion Criteria

Undergoing a non-emergency (elective) open surgical procedure, wherein a target bleeding site (TBS) was identified on soft tissue and a topical hemostat was indicated, baseline hemoglobin ≥ 8.0 g/dL, 

Exclusion Criteria

Infection in the anatomic surgical area, mild or severe TBS, history of severe reactions to any blood-derived product, reported sensitivity to any components of FS Grifols or Surgicel®, pregnant

Methods

Patients were randomized (1:1) to receive either FS Grifols or Surgicel®. Patients randomized to FS Grifols received a thin layer of FS Grifols applied on the TBS surface either by dripping or spraying. The approximate total amount of FS Grifols applied to the TBS was recorded. Patients randomized to Surgicel® received application according to package insert instructions (e.g., use only as much as is necessary for hemostasis, holding it firmly in place until bleeding stops) and the surgeon's clinical practice. Alternative hemostatic products or treatments were not allowed during the 10-minute observational period unless there was brisk and forceful bleeding at the TBS that jeopardized patient safety.

Time to hemostasis (TTH) was measured from the start of treatment application (TStart) to the achievement or failure of hemostasis at the end of the observational period. TTH was classified into one of six defined hemostatic time categories (HCTs): ≤2 minutes, >2 to ≤3 minutes, >3 minutes to ≤4 minutes, >4 to ≤5 minutes, >5 to ≤7 minutes, >7 to ≤10 minutes, or non-HTC (persistent bleeding at the TBS beyond the 10-minute observational period).

If the lower limit of the two-sided 95% confidence interval (CI) exceeded 0.8, non-inferiority was deemed to be demonstrated. If non-inferiority was established, superiority was additionally claimed if the two-sided 95% CI was entirely above 1.

Duration

Follow-up: 3 months ± 7 days after surgery

Outcome Measures

Primary: proportion of subjects who achieved hemostasis at the TBS by 4 minutes (T4) following TStart without the occurrence of re-bleeding until the completion of the surgical closure

Secondary: TTH, cumulative proportion of patients achieving hemostasis at the TBS by each of the six defined HTCs, prevalence of treatment failures

Baseline Characteristics

 

FS Grifols (n= 116)

Surgicel® (n= 108)

   

Age, years

48 47    

Female

87 (75%) 86 (79.6%)    

White

93 (80.2%) 81 (75.0%)    

Weight, kg

76 78    

Results

Endpoint

FS Grifols (n= 116)

Surgicel® (n= 108)

Relative risk (95% CI)

p-value

Hemostasis by T4 at TBS

Intention-to-treat population

Per-protocol population



96/116 (82.8%)

87/104 (83.7%)



84/108 (77.8%)

78/102 (76.5%)



1.064 (0.934 to 1.213)

1.094 (0.954 to 1.255)



N/A

N/A

Hemostasis

By 2 minutes

By 3 minutes

By 5 minutes

By 7 minutes

By 10 minutes



62 (53.4%)

88 (75.9%)

97 (83.6%)

100 (86.2%)

104 (89.7%)



47 (43.5%)

65 (60.2%)

85 (78.7%)

88 (81.5%)

90 (83.3%



1.228 (0.934 to 1.615)

1.260 (1.048 to 1.516)

1.062 (0.936 to 1.206)

1.058 (0.942 to 1.118)

1.076 (0.969 to 1.194)



0.144

<0.05

0.394

0.367

0.176

Adverse Events

Common Adverse Events: procedural pain (54.4% vs. 54.4%), procedural nausea (14.2% vs. 19.6%), nausea (13.6% vs. 11.4%), constipation (11.2% vs. 7.0), pyrexia (8.3% vs. 9.5%), anemia (7.7% vs. 8.9%), hypertension (7.7% vs. 7.6%), vomiting (7.1% vs. 5.7%), hypotension (6.5% vs. 3.2%), pruritus (5.3% vs. 6.3%), incision site pain (5.3% vs. 4.4%), cervicitis (5.3% vs. 3.8%), urinary tract infection (0.6% vs. 5.7%)

Serious Adverse Events: 10.1% vs. 11.4%

Percentage that Discontinued due to Adverse Events: Two patients in the FS Grifols and one patient in the Surgicel® experienced serious adverse events with outcome of death.

Study Author Conclusions

This prospective, single-blind, randomized comparative study shows that FS Grifols is non-inferior to Surgicel®, with similar AEs, providing data for its safe and effective use as an adjunct to hemostasis in soft tissue open surgery.

InpharmD Researcher Critique

The decision to apply fibrin sealants was subjective according to the severity of the bleeding, which may have confounded results.



References:

Lakshman S, Aqua K, Stefanovic A, et al. A Prospective, Single-Blind, Randomized, Phase III Study to Evaluate the Safety and Efficacy of Fibrin Sealant Grifols as an Adjunct to Hemostasis During Soft Tissue Open Surgery. J Invest Surg. 2020;33(3):218-230. doi:10.1080/08941939.2018.1489917