Surgicel Snow in Gynecological Surgery
Phase: NA
Conditions: Laparoscopic Hysterectomy
Sponsor: Danbury Hospital

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Protocol Title: Surgicel Snow in Gynecological Surgery 
 
NCT number: NCT02908841 
 
Version Date: 08/11/2016  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Background:  
Surgicel Snow is a topical hemostatic agent for use during surgical procedures.  Topical 
hemostatic agents are classified into four categories based upon functional characteristics: 
mechanical agents, biological agents, flowable sealants, and fibrin sealants.  The mechanical 
agents are further subcategorized by origin of component monomers including porcine 
gelatin, bovine collagen, oxidized regenerated cellulose, and polysaccharide spheres.  The 
effectiveness, risk profile, and mechanism of action differ by hemostatic classification.  Like 
the other mechanical agents, Surgicel Snow forms a physical barrier that blocks blood flow 
while providing a large surface area for the rapid formation of a fibrin clot.  As a mechanical 
agent derived from oxidized regenerated cellulose, Surgicel Snow shares with other 
mechanical hemostatic agents, the benefits of a favorable risk profile.  It is relatively 
inexpensive, rapidly absorbed (14 days), rarely induces a local inflammatory response or 
fibrosis, and no reported potential for inducing immunological response or anaphylaxis.  A 
possible added benefit of oxidized regenerated cellulose topical hemostats is the 
antimicrobial effect of the lowered pH with the barrier layer (1).  As is the case for all 
mechanical agents, the effectiveness of Surgicel Snow is limited by the need of an intact 
coagulation mechanism, as it will not enhance the rate of thrombus formation without 
adequate levels of coagulation factors.  Surgicel Snow is generally used for minimal to mild 
bleeding from focal or widespread sources (2). 
  
The use of oxidized regenerated cellulose has been shown to reduce length of stay and 
resource utilization in cardiovascular and neurosurgical procedures (3).  With the exception 
of a small number of studies on myomectomy and conservative ovarian surgery (4-9), there 
is a paucity of evidence to support a benefit associated with the use of topical hemostats 
during gynecological surgery.  Although it is known that all of the agents presently 

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approved by the FDA are capable of shortening the bleeding time associated with surgical 
incisions, there are no studies to show comparative efficacy or clinical impact with respect 
to estimated blood loss, transfusion rates or overall cost of care (10).  Because of this lack of 
quality studies, there are few guidelines available for usage by clinical situation or by type 
of hemostatic agent.  Notwithstanding the generally high level of confusion among 
gynecologic surgeons concerning indications for using topical hemostatic agents, it appears 
that these agents are being used with increasing frequency (11).  The need for additional 
studies on the clinical impact of topical hemostatic agents during gynecologic surgery is 
clear. 
  
The gynecologic procedures that provide the most interesting opportunities for clinical 
research on topical hemostatic agents at present are hysterectomy, resection of deeply 
infiltrating endometriosis, surgical management of active pelvic inflammatory disease, and 
sacrocolpopexy.  These procedures share the requirement for dissection of the pelvic 
retroperitoneal spaces and are thereby associated with the risk of venous oozing adjacent 
to vital structures that limit the options for standard hemostatic methods. The 
retroperitoneal space of the pelvis (12) include the pararectal space, paravesical space, 
retropubic space, vesicovaginal space, rectovaginal space, and the presacral space (Triangle 
of Cote).  The retroperitoneal spaces are potential spaces that are created by dissection to 
facilitate the identification, mobilization, and excision of pelvic retroperitoneal structures 
such as the ureters, iliac vessels, lymphatics, deeply invasive endometriosis, and residual 
ovaries.  As the boundaries between structures of different embryological origins, the 
retroperitoneal spaces are generally avascular.  These avascular planes are bordered by 
richly vascularized structures that can be easily disrupted by the dissection required to 
develop these space or by manipulation of the structures bordering these spaces.  Bleeding 

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from the development of the pelvic retroperitoneal space is generally minimal and 
frequently, but not always, requires no specific hemostatic measures.  Bleeding from 
mobilization or excision of retroperitoneal structures, such as during lymphadenectomy 
and dissection of cervical or intra-ligamental leiomyoma, has a greater propensity for blood 
loss and will frequently require standard hemostatic measures such as vascular clips, suture 
ligation, or electrosurgical methods for control.  Although retroperitoneal bleeding occurs in 
a minority of the proposed procedures, the nature of bleeding within the retroperitoneal 
space is similar among the three procedures proposed.   
 
The results of extensive bleeding in the retroperitoneal spaces include significant blood loss 
with dissection along the extraperitoneal fascial planes, as well as intraperitoneal collection, 
hematoma, and abscess.  Patients with postoperative pelvic collections may present with 
symptoms of fever, rectal pain, or lower abdominal pain (13).  Treatment often requires IR 
(interventional radiology) drainage and readmission for inpatient parenteral antibiotic 
therapy.  The initial approach to hemostasis in the pelvis depends on the nature of bleeding 
encountered.  When bleeding is encountered during pelvic dissection, evaluation of the 
extent and sources of bleeding, as well as its anatomic location and proximity to vital 
structures are the first requirements.  The process of evaluating bleeding requires 
inspection of the bleeding sites augmented by irrigation, suctioning, and blotting with 
gauze.  Through this process, the rate (minimal, mild, moderate, and severe)0F1, distribution 
                                                        
1 Estimated as blood loss in 10 second observation time as follows 
1. minimal less than 2 cc 
2. mild 2-3 cc 
3. moderate 3-5 cc 
4. severe >=5 

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(local vs. diffuse), anatomic site (i.e., if in close proximity to vital structures), and source of 
blood loss (small arterial, venous or capillary) is ascertained.   
 
Objectives:  
This study would examine the efficacy of Surgicel Snow vs. direct compression in the 
control of capillary, venous, and small arterial hemorrhage when ligation or other 
conventional methods of control are impractical or ineffective in patients undergoing 
laparoscopic or robotic assisted laparoscopic hysterectomy.  The intraoperative inclusion 
bleeding characteristics are minimal and mild retroperitoneal bleeding and moderate 
retroperitoneal bleeding that has been adequately reduced by standard surgical methods. 
 
Design:  
The proposed research method will use a randomized, concurrent control, no blinding. We 
are limiting our study to retroperitoneal dissection hysterectomy only to control for the 
expected variation in bleeding among the potential procedures.  We propose to randomize 
60 patients - 30 to the treatment group and 30 to the control group.  The patients 
participating in this study would be patients scheduled for hysterectomy at Norwalk 
Hospital and Danbury Hospital under the direction of Dr. Thomas Rutherford, Dr. John 
Garofalo, and Dr. Robert Samuelson.  
 
The patient population is drawn from throughout the State of Connecticut.  Indications for 
hysterectomy will include benign, complex benign uterine and adnexal pathology, as well as 
gynecologic oncology cases.  Vaginal hysterectomy procedures and open abdominal 
procedures will be excluded. Complex benign pathologies are those that are likely to require 
retroperitoneal dissection and or ureterolysis, (e.g., cervical leiomyoma, endometriosis, etc. 

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Peritoneal access for hysterectomy will include open laparotomy, standard multiport 
laparoscopy, and robotic assisted laparoscopy.  All patients scheduled for indicated 
procedures will be screened for inclusion. Once consented, patients will be randomized to 
the control group or the treatment group. The control group will receive standard of care, 
and the treatment group will receive Surgicel Snow. A random number generator will be 
used to determine test vs. control in blocks of 10.  
 
For patients with qualifying bleeding (rated on initial evaluation as at least “mild”) who 
have been randomized to receive Surgicel Snow, a single thin layer of dry Surgicel Snow will 
be applied over the area of bleeding and positioned firmly in direct contact to the areas of 
bleeding with blunt surgical instruments. Surgicel Snow will be left in the cavity to be 
absorbed. Dry gauze will not be placed over the material.  No adjuncts will be added to the 
enhance hemostasis, but patients with small arteriolar bleeding will have pressure 
maintained on the bleeding site for 60 seconds.   Control patients will be managed with 
direct compression with gauze pads or laparotomy pads for four minutes.  If hemostasis is 
not achieved by compression after four minutes, the source and rate of bleeding will be 
reevaluated and management will be determined by the surgeon. If the surgeon uses 
SurgicelSnow to achieve hemostasis at some point after 4 minutes, the patient will be 
included in the control group, but his/her data will be and flagged for the analysis.   
Hemostasis will be defined as the absence of free-flow bleeding, specified as no new 
appearance of blood from the bleeding site.  Pinpoint or petechial bleeding that appears but 
does not grow, or saturation of blood into the hemostat that may have occurred prior to or 
during the application of hemostatic agent that did not spread during the observation 
period, will not be considered free-flow bleeding.  Control and treatment patients who do 

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not require a topical agent to achieve hemostasis, thus not requiring a bleeding evaluation 
will be excluded from the study.   
For control patients, hemostasis failures at 4 minutes will be managed as per judgment of 
the primary surgeon, most likely be the use of a topical sealant.  For treatment patients, 
hemostatic failure at 4 minutes will be reassessed for rate of blood loss and if the rate of 
loss is estimated at less than 25 cc per minute, additional observations will be made at 7 
and 10 minutes.  If failure of hemostasis at 4 minutes with an estimated loss of ≥25 cc/min, 
patient will be managed as per judgment of surgeon. Persistent bleeding at the 10 minute 
observation point will be treated as per the surgeon’s judgment.  The nature of the bleeding 
will be recorded throughout the study. 
 
Follow-up visits at 2 weeks (+/- 1 week) and 6 weeks (+/- 1 week) will be scheduled to 
determine if the patient has had a symptomatic collection or pelvic abscess.  All subsequent 
procedures will be recorded, particularly those to manage bleeding. 
 
The physician will take the time to describe the potential risks and benefits of the study as 
outlined in the consent form, to the patient. This will be reiterated by the assigned research 
coordinator. Only patients who have signed appropriate consent forms will be included in 
the study.  Trained coordinators will be used and all standard safety protocols of the Clinical 
Research Department will be followed.  The trained research coordinators will collect data 
at time of surgery. Should there be an adverse event, this will be documented and reported 
to the Principal Investigator (PI) and the IRB. 
 
 
 

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Intraoperative Flow Diagram 
 
Selection and withdrawal of subjects:  
Inclusion criteria: 
1. Women ≥18 years of age 
2. Women scheduled for standard multiport laparoscopic, single site laparoscopic, and 
robotic assisted laparoscopic hysterectomy.  
2. Sites of surgery include Norwalk Hospital and Danbury Hospital.   
3. Indication for surgery includes benign, complex benign, and malignant conditions. 
4. Signed informed consent 

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Exclusion criteria: 
1. Vaginal hysterectomy or open abdominal hysterectomy;  
2.  Congenital or acquired coagulation disorder including recent (within 7 days of surgery) 
therapeutic anticoagulation or use agents affecting platelet function, other than low dose 
aspirin.  (Preoperative prophylactic heparin is not an exclusion criterion.) 
3. Hysterectomy at the time of sacrocolpopexy. 
4. Ovarian cancer 
 
Participants may be withdrawn from the study at their request.  Should a participant choose 
to withdraw from the study, no further clinical data will be collected on that patient and 
there will be no subsequent follow-up.  In the event that a participant chooses to withdraw 
from the study, an additional study participant may be recruited to replace her. 
 
Treatment of subjects: 
Participants may continue all regular medications before and during the study.  
The consent process will be incorporated into the consult visit prior to surgery.   
 
Assessment of Efficacy: 
The proposed clinical endpoints are time to hemostasis and failure to achieve hemostasis.  
Because multiple factors other than retroperitoneal bleeding contribute to the total 
intraoperative blood loss, we believe that the intraoperative estimated blood loss is not a 
pure indicator of the efficacy of a topical hemostatic agent for control of retroperitoneal 
bleeding.  The determination of the primary endpoint of time to hemostasis is based upon a 
modification of the methods used by Hutchinson, et al in Cellulose (15).  Secondary 
endpoints will include total operative time, intraoperative blood loss, blood transfusion, 
postoperative hemoglobin decrease, rate of postoperative symptomatic fluid collection, 

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postoperative pelvic abscess, and total cost for care from day of operation until six week 
(+/- 1 week) postoperative visit.  
 
Assessment of Safety: 
Whereas Surgicel Snow is generally used for minimal to mild bleeding from focal or 
widespread sources, should there be an adverse event related to the study conduction, this 
will be documented and reported to the study’s PI.  The PI will evaluate whether the 
adverse event involves risk to participants or others.  If so, the PI may choose to change the 
protocol, change the consent form, require that all participants already enrolled be notified 
and/or re-consented, or suspend or terminate the study. 
 
Statistical Analysis:  
All data will be collected in paper format and transferred to an electronic database where all 
PHI will be removed and replaced with a study number.  After conducting descriptive 
analyses, we will compare the treatment and control group on the primary and secondary 
outcomes.  Multivariate analyses will be used to control for any observed variation between 
the study groups.  Statistical significance will be assessed at p <0.05.   
It is anticipated that 60 participants will be enrolled in this study. The study will be 
terminated once all patients have completed their 6 week (+/- 1 week) follow-up post-
surgery.  
 
Direct Access to Source Data Documents: 
The study’s data collection sheet outlines when each data point will be collected.  The 
study’s PI, primary study coordinator, and co-authors will have access to all study data.  
These data will be used for study purposes only, and will be stored on a password-

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encrypted drive at the Danbury Hospital Department of Research office.  Data may be 
released to regulatory agencies as necessary, including the US Food and Drug 
Administration, Department of Health and Human Services agencies, BRANY, the Danbury 
Hospital IRB, accrediting agencies, and data safety monitoring boards. 
 
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