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COBRA Trial Has ‘Very Provocative’ Preliminary Outcomes, but Long-Term Still Unclear

By Christina Frangou

Chicago—Interim results from a prospective multicenter study demonstrate that use of a bioabsorbable mesh in complex ventral hernia repair results in favorable early outcomes with a hernia recurrence of 4% and a wound infection of 22% after a mean follow-up of nine months.

If the results hold up in the long term, the findings could change the way contaminated complex ventral hernias are approached by making repair possible with a bioabsorbable synthetic mesh. However, it’s too early to know from this industry-sponsored trial if bioabsorbable synthetic meshes do have a future in these repairs, said experts.

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“The bioabsorbable mesh is a synthetic mesh and can be a nidus for microorganisms. Long-term results are going to be very important but the preliminary results are very encouraging,” said Kamal Itani, MD, professor of surgery at Boston University School of Medicine and chief of surgery for the VA Boston Health System, after reviewing the study.

The COBRA (Complex Open Bioabsorbable Reconstruction of the Abdominal Wall) trial is the first large study to focus on bioabsorbable synthetic meshes in complex ventral hernia repairs.

Biologic meshes are typically used in these repairs and can cost as much as $10,000. Synthetic meshes cost considerably less but the outcomes in these hernia repairs are unknown.

Lead study author Michael Rosen, MD, associate professor of surgery and director of the Case Comprehensive Hernia Center at Case Western Reserve University, Cleveland, called the preliminary results “very provocative,” adding that bioabsorbable meshes may be a cost-effective alternative to a very expensive procedure.

“Bioabsorbable costs one-third of the biologic meshes usually used in these repairs. If these results hold up in the long term, bioabsorbable mesh may be a viable alternative to biologic mesh.”

The trial was designed to assess outcomes after use of a bioabsorbable synthetic mesh to reinforce the midline fascial closure in single-stage, open, clean-contaminated and contaminated ventral hernia repairs.

Investigators from nine centers in the United States and Europe enrolled 100 patients since March 2011 and will follow the participants for two years. All patients had a hernia defect of 9 cm2 or greater and a clean-contaminated or contaminated operative field due to a concomitant procedure, open wound or removal of infected mesh.

Preliminary results from the study were presented at the 2012 Clinical Congress of the American College of Surgeons (ACS). At the time, data were available for 34 men and 44 women with a mean age of 58 years and a mean body mass index of 28 kg/m2. They were followed for a mean of nine months (range, one-17 months).

Seventeen wound events (22%) were reported. Thirteen of these were infections, representing a 15% infection rate. Eight infections were superficial; two were attributed to suture-related abscesses. Five deep infections occurred, three following seroma aspiration. Twelve infections resolved in an average of 33 days (one-126 days) with conservative treatment. One patient was still experiencing a superficial infection at the time of the report and a superficial wound debridement was planned. No bioabsorbable material was exposed or required debridement or excision.

Additionally, one patient had a recurrent bowel obstruction as a result of resections performed during the initial hernia repair. The obstruction was resolved with revision of the anastomosis.

One patient developed a seroma that spontaneously resolved. Another patient developed a hematoma, which required aspiration. Three patients (4%) developed hernia recurrences with an average defect size of 177 cm2, which is acceptably low, said investigators.

It’s unreasonable to compare directly the recurrence rate or wound event rate from this study with those for biologic meshes. Very few published studies have examined recurrence rates after biologic grafts in complex hernia cases, and these included very few patients. Reported recurrence rates range from 0 to more than 50%.

The most significant trial of a biologic mesh, the RICH (Repair of Infected or Contaminated Hernias) study, was performed using Strattice™ Reconstructive Tissue Matrix (LifeCell). In 64 of 80 patients who underwent a single-stage hernia repair with the Strattice, surgeons successfully closed the fascia during the repair. At 24 months of follow-up, 53 patients (66%) experienced 95 wound events. There were 28 unique, infection-related events in 24 patients and 22 hernia (28%) recurrences within two years of the repair (Surgery 2012;152:498-505).

Dr. Itani, who led the RICH study, cautioned against comparing the trials head-to-head. Still, he noted that patients who received the bioabsorbable synthetic meshes appear to have fewer infections at 30 days—15% versus 21%—and fewer seromas.

“These results are very encouraging. Biologics are far from a panacea in abdominal wall reconstruction. A good alternative to biologics which is less costly and has better long-term outcome would be welcome.”

Scott Helton, MD, director of hepatopancreatobiliary surgery at Virginia Mason Medical Center, Seattle, and also an investigator on the RICH study, said the COBRA trial reports that wound events occurred only half as often as what has been reported in other studies in similar high-risk patients. But, he said, that difference might not be due to the type of mesh.

The COBRA investigators are among the most experienced hernia surgeons in the world, and as such, they would be expected to have lower-than-average wound infections and recurrence, said Dr. Helton. Investigators provided few details on technique in their poster presentation at the ACS but Dr. Helton speculated that their preference for placing the mesh in the retrorectus position might be why their outcomes were so good. Both the RICH trial and other studies have shown that the retrorectus position is associated with low hernia recurrence. Finally, investigators selected patients very carefully for the study.

“There’s a combination of factors at play: good patient selection, optimal timing of surgery, the use of proper technique. All these things collectively, I think, contributed to the study’s good outcomes,” Dr. Helton said.

“What we can conclude is that if they do it this way with this material, these are their results, which are better than just about anything else that’s been published.”

The surgical repairs took a mean of 237±86 minutes. Most repairs, 94%, were in a retrorectus location with a mean defect size of 145±122 cm2. Patients spent a mean of nine days in the hospital and 11 days with drains in place.

In all, 56% of the study participants underwent a primary ventral hernia repair, whereas 44% had repairs done for recurrent hernias. Many patients underwent concomitant procedures at the same time as the hernia repair. These included bowel resections (27%), ostomy reversals (26%), infected mesh removals (23%), gastrointestinal (GI) fistula repairs (19%), urologic or gynecologic procedures (6%), diverting ostomy creations (4%) and cholecystectomies (4%).

The preoperative risk factors for contamination included contaminated wounds (81%), clean-contaminated wounds (19%), presence of a stoma (46%), presence of GI fistula (18%), presence of nonhealing abdominal wound (23%) and previously implanted mesh (38%).

The patients in the study will be followed for two years and the results will be updated as they become available.

The mesh used in the study was GORE® BIO-A® Tissue Reinforcement and the study was funded by Gore.

Dr. Itani was the author of the RICH trial, which was sponsored by LifeCell. Dr. Helton receives honoraria from LifeCell for teaching and lectures. Dr. Rosen disclosed that he was a co-investigator on the RICH trial and is a speaker for Davol and LifeCell. He has received research grants from Cook, W.L. Gore, and Kensey Nash.