GUARDIX Sol 5g

Advanced Adhesion Barrier

RSUD Prof. Dr. Margono Soekarjo Purwokerto, 19 Oktober 2011

Taufik Akbar, Apt. Scientific Communication Medical Affairs Department Dexa Group

CSL Behring

Ebewe

Strategic Alliance Partners Dexa Medica Group

Beximco

UCB

Cobiosa Institut Rosell-Lallemand Karma Medica Delta Select

Bayer Schering Pharma Oy

Actavis

Tradimun

Minophagen Meiji Astellas Daiwa Tanabe Santen

Novartis Frutarom

Pfizer Madah Medica KV Pharmaceuticals Beckton Dickenson

Menarini Edmond Pharma

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Piramal Health Care Themis Dr Reddys Laboratories

Daewoong GSK Consilient Health IS Pharma

Standard Chem

Export Destinations

Dexa Operations:

Our Distributors:

Awareness of Postoperative Adhesion

Postoperative Adhesion
Definition
Adhesions are a type of scar tissue that may form an abnormal connection between organs and tissues after many types of surgical procedures. These injuries are normally caused by suturing, cauterization, and abrading tissues and organs during surgery.
Guardix Slide. Korea. 2010

Postoperative Adhesion
Epidemiology
- Intraperitoneal adhesions ranges from 67 to 93% after general surgical abdominal operations and up to 97% following open gynaecological pelvic procedures - Adhesions form between the wound and the omentum in over 80% of patients and these adhesions may involve the intestines in 50% of patients - United States, up to 70% of small bowel obstructions are due to adhesions - The incidence of small bowel obstruction has been reported to be as high as 10% after appendectomy, 6.4% after open cholecystectomy, and 10 to 25% after intestinal surgery
Cheung JPY, et al. ASIAN JOURNAL OF SURGERY ; 2009 32 (3):180-6

Postoperative Adhesion
Epidemiology
Abdomen and pelvis 90% of abdominal surgery, 55-94% of pelvic surgery 55% of ovary surgery, 36% of fimbrae surgery Spine 24% of failed back surgery syndrome caused by peridural scar Endometrium (D&C) 20~50% of endometrial synechiae occurred after D&C

Guardix Slide. Korea. 2010

Postoperative Adhesion

The American Journal of Surgery (2011) 201, 111-21

Postoperative Adhesion
Complications caused by adhesion at abdomen & pelvis
Complications Patients (operation) cases Ratio caused by adhesion

Small intestine atresia

5 Million cases (Digestive organ) 1 Million cases (Urinary organ)

4974 %

Stomach rupture Infertility Chronic pelvis pain 6 Millions of people

19 % 1520 % 2050 %

1. 2.

Ray NF, Denton WG, Thamer M, Henderson SC, Perry S. Abdominal adhesiolysis: inpatient care and expenditures in the U.S. in 1994. J. Am. Coll. Surg. 1998;186(1): 1-9. Van Goor H, Morbidity and mortality of inadvertent enterotomy during an adhesiotomy. British Journal of Surgery 2000; 87: 467-471

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Postoperative Adhesion
Feasible Adhesive Organs
1. Abdomen (intestine, peritoneum) 2. Pelvis (uterus, ovary, fallopian tubes, fimbria, endometrium etc) 3. Spine (nerve root) 4. Thoracic cavity (lung, heart, pleura)

Guardix Slide. Korea. 2010

Mechanism of Postoperative Adhesion

The American Journal of Surgery (2011) 201, 111-21

Postoperative Adhesion
Adhesion Mechanism

When tissue is injured, Macrophages, fibroblast and Fibrin matrix gather to the injured surface by inflammatory response

Macrophages make the basement of adhesion, fibrin matrix is developed, and fibroblast grows up, and then the formation of the blood vessel starts.

As the adhesion developed, it is increased blood vessel and systematized

With the progress of existed adhesion, The separation with the tissue became indefinite, and formed the densely bands

Guardix Slide. Korea. 2010

How to Prevents Postoperative Adhesion?

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Adhesion Barrier
Anti-adhesion methods
Meticulous surgical techniques Pharmaceutical agents: corticosteroids, NSAIDs Fluid instillations: dextran, carboxymethylcellulose, HA gel PEO (polyethylene oxide) solution, lactated Ringer's solution

Physical barriers:
Oxidized-regenerated cellulose

Expanded PTFE (polytetrafluoro ethylene) HA+CMC membrane Collagen sponge

Guardix Slide. Korea. 2010

GUARDIX Sol 5g
Advanced Adhesion Barrier

Product Information
Ingredient : Sodium Hyaluronate Sodium Carboxymethyl Cellulose Sterilization : EO (ethylene oxide)

Specification : 5 g 150-200 cm2

Storage : Room temperature Expiry Date : 24 months

Guardix Slide. Korea. 2010

Mechanism of Action

Guardix sticks to the internal tissues and separates the organs to help prevent them from attaching to one another as they heal

Once placed inside the body Guardix is reabsorbed within seven days, so it does not remain and does not need to be removed

Without Guardix
Guardix Slide. Korea. 2010

With Guardix

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Safety Profile
Test Sitotoksisitas Uji toksisitas akut Uji pirogenitas Uji sensitifitas dan reaktifitas intrakutan Hasil Keterangan Efek sitotoksisitas tidak terlihat Kematian maupun efek samping klinis tidak ditemukan Tidak terjadi perubahan suhu >0.5C Erythema dan edema tidak ada, sel inflamasi dan fibrogenesis tidak terlihat Tidak terjadi mutasi dari mikroorganisme (Salmonella thypimurium) SCE (Sister Chromatid Exchange) yang disebabkan oleh mutagenitas tidak terlihat Mikronukleus yang disebabkan oleh mutagenisitas tidak terlihat Nilai hematologi, liver, ginjal, paru-paru tidak berubah Tidak terjadi pertumbuhan bakteri dan fungi
Biorane Co., Ltd, Safety Test Report Guardix-sol; No. 2003-1

Uji genotoksisitas Uji toksisitas sub akut Uji sterilitas

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Application of Guardix
Obstetrics & Gynecology
1. Indication Uterus and related surgery, Laparoscopic surgery, Cesarian section. 2. How to use Apply Guardix to part of doubted adhesion area. Apply Guardix after intrauterine surgery.

Guardix Slide. Korea. 2010

Application of Guardix
Neuro Surgery/Orthopedic Surgery: Spine
1. Indication Laminectomy, discectomy etc. for using in every vertebra operation 2. How to use Even distribute to Dura area after vertebra surgery or after spinal nerve surgery

Guardix Slide. Korea. 2010

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Application of Guardix
Intraabdominal Surgery
1. Indication

Viscous and lubricant coating on operated sites after operation To minimize tissue adhesion on operated sites after operation (laparatomy, laparascopy)

2. How to use

Apply Guardix to part of doubted adhesion area

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Guardix Slide. Korea. 2010

Clinical Trial
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Intrauterine Surgery

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Objective :
The prospective, double blind study was performed to assess the efficacy of Hyaluronic acid + Sodium Carboxymethyl Cellulose (HA + CMC) gel in preventing the development of intrauterine adhesions (IUAs) following intrauterine surgery.

Method :
- A total of 64 patients with abortion, submucosal myoma, septate uterus were underwent intrauterine surgery. - Patients: - Group A, 10ml of Hyaluronic acid + Sodium Carboxymethyl Cellulose (HA + CMC) intrauterine cavity,

- Group B, 10ml of saline was applied

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Result

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INTRAABDOMINAL SURGERY

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Comparison of intraperitoneal honey and sodium hyaluronate-carboxymethylcellulose for the prevention of postoperative intra-abdominal adhesions

Background:

This study compares the use of honey with a standard bioresorbable membrane (HA-CMC) to prevent the formation of posoperative intraabdominal adhesion Laparotomy divided into three groups :

Methode:

Group 1 (control) represented the cecal abrasion group, with no intraperitoneal administration of any substance. Group 2 (honey group) underwent cecal abrasion and intraperitoneal administration of honey. Group 3 (hyaluronate-carboxymethylcellulose group) underwent cecal abrasion and intraperitoneal hyaluronate-carboxymethylcellulose application

Emre A. CLINICS 2009;64(4):363-8

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Comparison of intraperitoneal honey and sodium hyaluronate-carboxymethylcellulose for the prevention of postoperative intra-abdominal adhesions

Emre A. CLINICS 2009;64(4):363-8

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Comparison of intraperitoneal honey and sodium hyaluronate-carboxymethylcellulose for the prevention of postoperative intra-abdominal adhesions Result
P<0.05 HA-CMC vs control

Intra-abdominal adhesions and histopathological fibrosis scores

Emre A. CLINICS 2009;64(4):363-8

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BACKGROUND: Postoperative abdominal adhesions are associated with numerous complications, including small bowel obstruction, difficult and dangerous reoperations, and infertility. A sodium hyaluronate and carboxymethylcellulose was developed to reduce formation of postoperative adhesions. The objectives of our prospective study were to assess the incidence of adhesions that recurred after a standardized major abdominal operation using direct laparoscopic peritoneal imaging an-d to determine the safety and effectiveness of HA+CMC in preventing postoperative adhesions.
STUDY DESIGN: Eleven centers enrolled 183 patients with ulcerative colitis or familial polyposis who were scheduled for colectomy and ileal pouch-anal anastomosis with diverting-loop ileostomy. Before abdominal closure, patients were randomly assigned to receive or not receive HA+CMC placed under the midline incision. At ileostomy closure eight to 12 weeks later, laparoscopy was used to evaluate the incidence, extent, and severity of adhesion formation to the midline incision.

Becker JM, et al. J Am Coll Surg. 1996 Oct;183(4):297-306

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Result

CONCLUSIONS: HA+CMC was safe and significantly reduced the incidence, extent, and severity of postoperative abdominal adhesions.

Percentage of Patients (%)

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Becker JM, et al. J Am Coll Surg. 1996 Oct;183(4):297-306

Neuro Surgery

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Neuro Surgery Clinical Trials Protocol

Clinical trial target & classification
1) Age between 20 to 60 2) Patients who are going to have the first operation related to neuromuscular disease such as unilateral herniated, lumbar intervertebral disk removal 3) Classification : Randomly allocate experiment group with adhesion barrier and control group with not using adhesion barrier according to table of random numbers, n=64

Clinical trials on effectiveness evaluation variation

1. Major evaluation deviation : 6 weeks after operation define 5 levels according to scar grade by MRI. Comparison between control and experiment groups 2. Supplement evaluation deviation : 1 and 6 weeks after operation, check clinical symptoms

(Weber evaluation method, Mixed markeing method, Walking evaluation, Major symptoms
evaluation, Normal activity evaluation) in comparison to control and experiment groups.
Bioraine, A clinical study to evaluate the efficacy and safety of GUARDIX-SL for prevention of adhesion following Spinal Surgery; 2006, 36 39

Neuro Surgery Clinical Trials Protocol

1. Effectiveness evaluation method

Grade 0 1 2 3 4

Scar formation No/trace scar 0% < scar 25% 25% < scar 50% 50% < scar 75% 75% < scar 100%

(1) Major evaluation variation MRI scar grade (2) Supplement evaluation variation Symptom evaluation method
Weber method Very good Good Moderate Poor

Patients are very much satisfied Patients are satisfied and pain is decreased Patients are dissatisfied, partly difficult to work Patients are not able to work due to chronic lumbago & sciatica

Bioraine, A clinical study to evaluate the efficacy and safety of GUARDIX-SL for prevention of adhesion following Spinal Surgery; 2006, 36 39

Neuro Surgery Clinical Trials Result

(2) Effectiveness Evaluation (General)

Comparison on average points of scar grade after

6 weeks (t-test)
MRI Scar score (6 weeks after operation) (N) p-value

Scar grade average (6 weeks later)

Average
Control group(28) Guardix group(30) 2.17 0.97

Standard deviation 0.889 0.000 0.795

Control group Guardix group

Comparison scar grade distribution after 6 weeks

MRI Scar score(6 weeks after operation, N/%) 0 Control group Guardix group Tot 1/3.4 9/29 10 1 5/17.2 14/48.4 19 2 11/41.4 6/19.4 17 3 9/34.5 1/3.2 10 4 1/3.4 0 1 Tot 28 30 58

Control Guardix

Bioraine, A clinical study to evaluate the efficacy and safety of GUARDIX-SL for prevention of adhesion following Spinal Surgery; 2006, 36 39

Neuro Surgery Clinical Trials Result

(2) Effectiveness Evaluation (General) Scar grade(0,1,2=Effective, 3,4=No effective) MRI scar grade(6 weeks after operation, N/%) Effective Control group Guardix group Total 18/64.3 29/96.7 47 No effective 10/35.7 1/3.3 11 Total 28 30 58

(Fishers exact test p=0.002)

When scar grade is high, scar presses nerve and causes higher risk of pain

Bioraine, A clinical study to evaluate the efficacy and safety of GUARDIX-SL for prevention of adhesion following Spinal Surgery; 2006, 36 39

Neuro Surgery Clinical Trials Result

(2) Effectiveness Evaluation (General) - Weber evaluation method (chi-square test)

1 week after operation (p=0.116) Items Explanation Patients are not able to work due to chronic lumbago and sciatica Patients are dissatisfied, difficult to work Patients are satisfied, decreased pain Patients re very much satisfied Control group 0/0 Experimen t group 0/0 Total 6 weeks after operation (p=0.007) Control group 0/0 Experiment group 0/0 Total

Poor

Moderate

18/(64.3%)

15/(50%)

33

15/(53.6%)

10/(33.3%)

25

Good
Very good Tot

7/(25.0%)
3/(10.7%) 28

5/(16.7%)
10/(33.3%) 30

12
13 58

6/(21.4%)
7/(25%) 28

1/(3.3%)
19/(63.3%) 30

7
26 58

Bioraine, A clinical study to evaluate the efficacy and safety of GUARDIX-SL for prevention of adhesion following Spinal Surgery; 2006, 36 39

CONCLUSION NEURO SURGERY

(1) Effectiveness
1) 2) 3) Control and Guardix group shows differences on 6 weeks after operation scar grade which is major evaluation deviation. Control and Guardix group shows differences according to Supplement evaluation deviation clinical symptom point & Weber evaluation method. Effectiveness was approved by general effectiveness evaluation

(2) Safety
1) 2) No severe side effects detected from Yongdong Severance Hospital and Hanyang University Medical Center Guardixsol is claimed that safe according to safety evaluation

Bioraine, A clinical study to evaluate the efficacy and safety of GUARDIX-SL for prevention of adhesion following Spinal Surgery; 2006, 36 39

THANK YOU
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