A multicentre, randomised, controlled trial to assess the safety, ease of use, and reliability of hyaluronic acid/carboxymethylcellulose powder adhesion barrier versus no barrier in colorectal laparoscopic surgery

Stéphane V Berdah, Christophe Mariette, Christine Denet, Yves Panis, Christophe Laurent, Eddy Cotte, Nöel Huten, Eliane Le Peillet Feuillet, Jean-Jacques Duron, Stéphane V Berdah, Christophe Mariette, Christine Denet, Yves Panis, Christophe Laurent, Eddy Cotte, Nöel Huten, Eliane Le Peillet Feuillet, Jean-Jacques Duron

Abstract

Background: Intra-peritoneal adhesions are frequent following abdominal surgery and are the most common cause of small bowel obstructions. A hyaluronic acid/carboxymethylcellulose (HA/CMC) film adhesion barrier has been shown to reduce adhesion formation in abdominal surgery. An HA/CMC powder formulation was developed for application during laparoscopic procedures.

Methods: This was an exploratory, prospective, randomised, single-blind, parallel-group, Phase IIIb, multicentre study conducted at 15 hospitals in France to assess the safety of HA/CMC powder versus no adhesion barrier following laparoscopic colorectal surgery. Subjects ≥18 years of age who were scheduled for colorectal laparoscopy (Mangram contamination class I‒III) within 8 weeks of selection were eligible, regardless of aetiology. Participants were randomised 1:1 to the HA/CMC powder or no adhesion barrier group using a centralised randomisation list. Patients assigned to HA/CMC powder received a single application of 1 to 10 g on adhesion-prone areas. In the no adhesion barrier group, no adhesion barrier or placebo was applied. The primary safety assessments were the incidence of adverse events, serious adverse events, and surgical site infections (SSIs) for 30 days following surgery. Between-group comparisons were made using Fisher's exact test.

Results: Of those randomised to the HA/CMC powder (n = 105) or no adhesion barrier (n = 104) groups, one patient in each group discontinued prior to the study end (one death in each group). Adverse events were more frequent in the HA/CMC powder group versus the no adhesion barrier group (63% vs. 39%; P <0.001), as were serious adverse events (28% vs. 11%; P <0.001). There were no statistically significant differences between the HA/CMC powder group and the no adhesion barrier group in SSIs (21% vs. 14%; P = 0.216) and serious SSIs (12% vs. 9%; P = 0.38), or in the most frequent serious SSIs of pelvic abscess (5% and 2%; significance not tested), anastomotic fistula (3% and 4%), and peritonitis (2% and 3%).

Conclusions: This exploratory study found significantly higher rates of adverse events and serious adverse events in the HA/CMC powder group compared with the no adhesion barrier group in laparoscopic colorectal resection.

Trial registration: ClinicalTrials.gov NCT00813397. Registered 19 December 2008.

Figures

Figure 1
Figure 1
Patient disposition. ITT, intent-to-treat.
Figure 2
Figure 2
Ease of use and reliability.(A) Ease of use of HA/CMC powder, as assessed by surgeons and nurses; (B) Reliability of HA/CMC powder, as assessed by surgeons. Overall manageability/reliability rates determined by overall number of cases scoring 3 or 4 on a 4-point scale (3 = easy or good, 4 = very easy or very good). For multi-component items, all were required to achieve a score of 3 or 4.

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