Adhesion Products
Please Note:
Information provided here is intended as a lay overview only and not as any fort of endorsement. Any product described here must be used by a medical doctorin accordance with the Instructions for Use and after taking a Patient's individual circumstances into account.
Reposted from the International Adhesion Society. Please visit the International Adhesion Society at;
http://www.adhesions.org/
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http://www.adhesions.org/products.htm
Products Approved by FDA for Adhesion Prevention, Reduction in Pelvice and/or Abdominal Cavities
* INTERCEED (TC7), made by Johnson & Johnson
Placed over the site of surgical injury, this knitted fabric dissolves within 30 days or so. The idea is that the sheet keeps organs apart that would otherwise stick (adhere) together. Once healing is complete, the sheet dissolves leaving the two organs properly separated.
Since 1989, it has been approved only for open (non-keyhole) gynecologic surgery with a good record of safety and effectiveness documented in this paper authored by Dr. Wiseman in 1999.
Althought it is not approved in the USA for use in laparoscopice (key-hole) surgery, INTERCEED is often used "off-label". Only small clinical studies to evaluate INTERCEED in laparoscopy have been performed with mixed results, possibly because almost perfect control of bleeding (required for INTERCEED's action) may not have been achieved, or INTERCEED was dislodged from its site of placement.
Early studies suggested that a small amount of Heparin added to the INTERCEED may not only enhance its action, but also overcome the detrimental effect that bleeding has on the beneficial action of INTERCEED. Unfortunately, this work was never pursued, neither was a modified form of INTERCEED, which also functioned better than the original INTERCEED, both in the absence and presence of bleeding.
* Seprafilm, made by Genzyme (previously called HAL-F)
This film looks like a thin, slightly brittle clear "fruit roll-up" that gels soon after contact with moist body tissues. It workes and is used in much the same way as INTERCEED, except that it is also approved for General Surgery. Like INTERCEED, it is not approved in the USA for laparoscopic use, aothought with considerable technical difficulty, it can be applied in laparoscopic surgery "off-label". Approved in 1996, it has now had a long history of safety and effectiveness similar to that of INTERCEED and a number of studies have preorted its use in a variety of procedures as well as the reduction of obstruction in some cases. It should not be wrapped around the bowel that has been cut open.
Some surgeons have made a gel by cutting small pieces of Seprafilm and mixing them with saline. A study conducted by Genzyme with a standard preparation called "SepraSpray" has yielded what appear to be unimpressive results.
* Adept, marketed by Baxter
Adept is a solution containing a carbohydrate polymer. A large volume (about 3 liters) is instilled into the abdominal cavity after surgery causing them to float, keeping them apart and and preventing them from sticking to each other. Because of the the composition of the product, liquid stays in the abdominal cavity for several more days that plain saline (salt) solutions commonly used by surgeons. Altough, it has the advantage that it is easy to apply and it can be used laparoscopically, the clinical data suggest that its effectiveness is at best marginally better than salt solutions, also when used in large volume.
It should be noted that small (eg 300ml) volumes of saline used to float tissues apart do not appear to reduce adhesions, thus the data from the Adept study does suggest that large volumes of physiological saline solutions may have some benefit in reducing adhesions.
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Products not approved for Adhesions prevention, but often used "off-label" (USA)
*Note that some of these products may be approved in countries other than the USA for adhesion prevention.
* Evicel - made by Johnson & Johnson
Evicel is a type of "Fibrin Glue", a two component product made from naturally occurring molecules extracted from human blood. It is mainly used to control bleeding during surgery. A number of studies in animals and humans have suggested that fibrin glues of various types can reduce adhesions. One study using a similar, but not identical experimental version of Evicel did suggest that indeed this type of fibrin glue may reduce adhesions in humans.
Evicel has the advantage that is can easily be applied laparoscopically, it can be spayed over a large area, is a naturally occurring material and can control mild bleeding.
Other types of fibrin glue, such as Tisseel and Tissucol, made by Baxter has also been used by some surgeons to reduce adhesions.
Note - there are a number of important differences between different types of fibrin glue that could determine how effective each type is.
* Coseal, made by Baxter
Coseal is a two-component, synthetic product used to seal leakage after surgery on blood vessels. It has been sprayed or applied over areas of surgical injury to reduce adhesions both in animal models and in one human trial with 71 patients undergoing myomectomy.
Coseal is marketed in Europe not only as a sealant, but also to prevent or reduce post surgical adhesions. Coseal is the same as what was formerly known as Adhibit.
* Surgiwrap, made by MAST BioSurgery
SurgiWrap (and its cousins OrthoWrap and CardioWrap) is a clear thin sheet of a dissolvable polymer similar to the kind used in dissolvable sutures. Full clinical studies of the kind conducted for INTERCEED or Seprafilm showing that it prevents or reduces adhesions have not been published and the product is approved in the USA to “reinforce soft tissues where weakness exists”.
Based primarily on animal studies and due to technicalities in the regulation of medical devices in the USA, the company’s marketing literature for the USA states that the product “Maintains a physical barrier between opposing soft tissues” and “Retains tensile strength for 6-8 weeks ensuring tissue separation during the critical wound healing period” and implies that the product reduces or minimizes “Soft Tissue Attachments”. The company’s literature for Surgiwrap intended for marketing outside the USA clearly claims that that SurgiWrap “prevents adhesion formation”. Naturally this difference has come to the attention of American surgeons who have traveled abroad and combined with a number of reports of adverse events such as the presence of a tissue reaction and the emergence of fragments of the sheet through the vagina which in one case was reported to have “lacerated her partner”, the product does not seem to enjoy popular use.
* PRECLUDE Peritoneal Membrane made by WL Gore
This product is being discontinued after December 2011. It never had the same kind of formal approval in the USA that INTERCEED, Seprafilm or ADEPT did of adhesion prevention, but after enjoying a fairly long period of use to reconstruct tissues, for example in hernia repair, the claim was added sometime in the early 1990s “for use in peritoneal reconstruction where minimal adhesions to a prosthetic material are desired”. PRECLUDE is a thin sheet of porous ePTFE (Teflon). Although some studies showed in the 1990s that Preclude (previously known as GoreTex surgical Membrane) reduced adhesions, many surgeons were reluctant to use it since it did not degrade and required a subsequent operation to remove it.
Versions of the product to minimize adhesions in cardiac and cranial (dural) surgery.
Drugs for Adhesion Prevention
There are no drugs currently approved for the prevention or removal of adhesions. Research in this area, most of it in animals, has focused mainly on drugs that can be applied directly into the abdominal cavity at the time of surgery. Most of the drugs tested have been directed either at the clotting process (preventing or reversing the deposition of fibrin - the natural glue that causes the initial attachment or adhesion of tissues) or the inflammatory process (which results in the formation of scar).
Some promising clinical data did suggest that heparin, when applied to INTERCEED may not only enhance its action but also overcome the detrimental effect that bleeding has on the beneficial action of INTERCEED. This was never pursued formally. Data from the pivotal general surgical trial for Seprafilm in patients with ulcerative colitis undergoing bowel surgery did suggest that patients receiving long term corticosteroids prior to surgery had lower rates of adhesion formation than those that did not. The effect was best seen in patients also receiving Seprafilm.
Studies, never published but widely known to have been performed in the 1980s and 1990s using Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) such as ibuprofen and tolmetin applied as solutions to the peritoneal cavity failed to result in the use of these drugs clinically.
tPA (Tissue Plasminogen Activiator) is a drug causes the dissolution of fibrin. Several small pilot studies had been performed but never pursued and a recent study failed to show a difference between treatment and control groups.
Newer generations of these classes of drugs have been tested in animals, bit so far without any formal clinical trials. Other classes of drugs tested include anti-oxidants, anti-angiogenic drugs, anti-fibrotic drugs, hormonal drugs, cytokine inhibitors, anti-inflammatory cytokines and COX-2 inhibitors.
Hernia and Tissue Reconstruction Meshes
A number of products exist for the reinforcement of soft tissues after major dissections, including hernias. Adhesions to these meshes is a common problem and the designers of some products have attempted to reduce this problem. These products may feature claims akin to those of the Preclude products and include (not exhaustively): Sepramesh (Davol) and PROCEED (Johnson & Johnson).
These and other surgical meshes may be used not only in hernia repair but also for Pelvic Organ Prolapse and Stress Urinary Incontinence. Regarding these kinds of products in general, FDA has issued a Public Health Notification on October 20 2008. There was also an update on July 13, 2011 regarding complications associated with some of these meshes that when used for hernia repair complications include “adverse reactions to the mesh, adhesions (when the loops of the intestines adhere to each other or the mesh), and injuries to nearby organs, nerves or blood vessels . Other complications of hernia repair can occur with or without the mesh, including infection, chronic pain and hernia recurrence.”
When used for Pelvic Organ Prolapse and Stress Urinary Incontinence the “most frequent complications included erosion through the vagina, infection, pain, urinary problems and recurrence of the prolapse and/or incontinence. In some cases, erosion of the mesh and scarring of the vagina led to discomfort and pain, including pain during sexual intercourse. Some patients needed additional surgery to remove the mesh that had eroded into the vagina. Other complications included injuries to nearby organs such as the bowel and bladder, or blood vessels.”
Since serious complications may occur with the use of Surgical Meshes it is important that you discuss with your doctor the risks and benefits of meshes as well as the type of mesh you may be given and its likelihood of producing an adverse reaction.
Other Products of Interest
* INSUFLOW, made by Lexion Medical
This novel device warms and humidifies the gases used to inflate the abdominal cavity during laparoscopic surgery. Because these cold, dry gases (carbon dioxide) are pumped at pressure they create a “wind-chill effect” which damages the surface layer (peritoneum) of organs in the abdominal cavity, a finding made in a study by Dr. Wiseman
Although the company does not claim it, it is well accepted that damage to the peritoneal layer contributes to the formation of adhesions. In addition use of the device helps to reduce hypothermia, postoperative pain and recovery time after surgery.
Products Marketed Outside of the USA
* SprayGel and SprayShield, made by Covidien
SprayShield is a synthetic two component product that forms a gel when applied to an organ. It is a modified version of SprayGel which demonstrated clinical effectiveness in reducing adhesions in small studies involving gynecologicand general surgery
Although all the details are unclear, it seems that SprayGel was discontinued because of problems relating to possible adverse reasons and the ability of the gel to form properly in the carbon dioxide environment that is used in laparoscopic surgery. SprayGel was, and SprayShield is marketed in Europe and we understand that a recent clinical trial in the USA was discontinued because the product failed to demonstrate efficacy.
* Hyalobarrier and Hyalobarrier Endo, made by Fidia Advanced Biopolymers, now Anika Therapeutics
Hyalobarrier, sometimes referred to as ACP Gel, is made from hyaluronic acid, a naturally occurring lubricant in the body.
Some small clinical trials have demonstrated effectiveness of in gynecologic surgery
* INTERCOAT, also known as Oxiplex AP made by Johnson & Johnson, licensed from Fziomed
This gel made is applied directly to raw surgical surfaces. Efficacy in gynecologic study was demonstrated in two small studies.
Study 1
Study 2
* Prevadh, made by Sofradim-Covidien in France
A collagen film and fleece composite that in animals was able to reduce adhesions even in the presence of bleeding and appeared safe in an uncontrolled clinical study of 78 patients.
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Products Marketed for reducing adhesions in procedures outside of the abdominal or pelvic cavities.
(This is not an exhaustive list, and it also includes products that have no formal claim of adhesion prevention)
Products (USA) Company Composition Indication
Repel CV Synthemed PLA/PEO Cardiac
TENOGLIDE Integra Collagen Tendon
Sepragel ENT
Seprapack
Genzyme Hyaluronic Acid Nasal / Sinus
Preclude Pericardial Gore ePTFE Pericardial
Preclude Dura Substitute Gore ePTFE
Products (non-USA) Company Composition Indication
INCERT-S Anika Hyaluronic Acid Spinal Surgery
ACP Gel Fidia Hyaluronic Acid Uterine Adhesions
MeroGel Fidia Hyaluronic Acid ENT
Oxiplex (also Medishield) Fziomed CMC/PEO Spinal
ADCON L Bioscompass Dextran Sulphate Spinal Surgery
ADCON T/N Biocompass Dextran Sulphate Tendon & Nerve Surgery
Products where data exists for prevention of clinical outcomes related to adhesions
Note that products may or may not have regulatory approval to market their products based on these studies. Only a selection of positive studies are shown below.
Prevention of IntraUterine Adhesions
Seprafilm Tsapanos et al., 2002
SprayGel Abbott et al., 2004
ACP Gel Guida et al., 2004
ACP Gel Acunzo et al., 2003
Intercoat Sardo et al., 2011
Prevention of adhesions after C Section
Seprafilm Fushiki H; Ikoma T; Kobayashi H, and Yoshimoto H. Efficacy of Seprafilm as an Adhesion Barrier in Cesarean Sections. Obstetric and Gynecological Treatment [Japanese]. 2005; 91(5):557-561.
Reduction of pain after adhesion-related surgery
Seprafilm Khaitan et al., 2003
Reduction of bowel obstruction
Seprafilm
Mohri et al., 2005
Fazio et al., 2006
Products where data exists for improvement of fertility after adhesion-related surgery (not necessarily with regulatory approval)
INTERCEED Sawada et al.,2000
Discontinued Products
* Sepracoat (also HAL-C), made by Genzyme was a hyaluronic acid based liquid that was used to coat tissue surfaces during surgery. It demonstrated clinical efficacy against de novo adhesions caused by tissue handling.
Its approval in the USA was rejected, and the product sold for a short time in Europe before poor sales led to its voluntary discontinuation sometime around 2000.
* INTERGEL, made by LifeCore, marketed by Johnson & Johnson was a gel of hyaluronic acid cross-linked with iron. With demonstration of clinical efficacy in the US and Europe .long it received FDA approval in 2002 after an unusual and controversial route but was withdrawn about one year later after reports of tissue reactions, increased rates of infection, late onset pain and some deaths.
Research conducted by the IAS suggested that these effects may have been more prevalent in patients who carried gene mutations for Haemochromatosis, a disorder of iron regulation, or women who had had prior hysterectomies, possibly because of an increased tendency to accumulate iron. Additional article.
* ADCON L is a gel containing Dextran Sulphate made by Gliatech for use in spinal surgery. It was approved by FDA in 1997. A version for tendon and nerve surgery was available in Europe and after a successful preclinical study conducted by Dr. Wiseman, a clinical trial, also designed by Dr. Wiseman had began to show promising results in pelvic surgery. Rapid sales of the ADCON L product began to be marred by a series of issues relating to problems in manufacturing, the company’s failure to report adverse events, and their alleged manipulation of data in a clinical trial. The company essentially placed in a “regulatory” limbo by FDA until it could, to FDA’s satisfaction put its house in order. A new management did indeed do this, but the effect of the FDA action forced the company to declare bankruptcy in 2002. Although not available in the USA, the product continues to be sold in Europe and elsewhere both in the ADCON L version and the ADCON T/N (tendon and nerve) version.
* Hyskon, made by Pharmacia, was a syrupy liquid used to expand the uterus during hysteroscpic evaluation. In the mid 1980s its was used off-label in the USA to prevent adhesions by pouring it into the abdominal cavity in the aim that it would lubricate raw tissue surfaces and prevent them from sticking. Some studies provided somewhat positive data, and while others provided the reverse and concerns of adverse reactions as well the emergence of other barriers led to its demise.
Adverse Reactions
Information about adverse reactions reported to FDA can be obtained through:
MAUDE - Manufacturer and User Facility Device Experience
If you think you have suffered an adverse reaction to any medical product, you should certainly contact your doctor and if necessary call the Emergency Services or go to the nearest Emergency Room. You are also free to report the event to the FDA by contacting the FDA's MedWatch Adverse Event Reporting program either online, by mail or FAX.
Online : MedWatch Online Voluntary Reporting Form (3500)
Mail : use postage-paid FDA form 3500 available at: MedWatch Forms
Mail to:
MedWatch
5600 Fishers Lane,
Rockville, MD 20852-9787
FAX: 1-800-FDA-0178
Interested in participating in a clinical trial?
Go to ClincalTrials.gov to search for clinical trials relating to adhesions, or any other therapeutic area.
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