Elsevier

The Lancet

Volume 377, Issue 9770, 19–25 March 2011, Pages 997-1003
The Lancet

Articles
Efficacy of dextranomer in stabilised hyaluronic acid for treatment of faecal incontinence: a randomised, sham-controlled trial

https://doi.org/10.1016/S0140-6736(10)62297-0Get rights and content

Summary

Background

Injection of a bulking agent in the anal canal is an increasingly used treatment for faecal incontinence, but efficacy has not been shown in a controlled trial. We aimed to assess the efficacy of injection of dextranomer in stabilised hyaluronic acid (NASHA Dx) for treatment of faecal incontinence.

Methods

In this randomised, double-blind, sham-controlled trial, patients aged 18–75 years from centres in USA and Europe were randomly assigned (2:1) to receive either transanal submucosal injections of NASHA Dx or sham injections. Randomisation was stratified by sex and region in blocks of six, and managed with a computer generated, real-time, web-based system. Patients and investigators were masked to assignment for 6 months when the effect on severity of faecal incontinence and quality of life was assessed with a 2-week diary and clinical assessments. The primary endpoint was response to treatment based on the number of incontinence episodes. A response to treatment was defined as a reduction in number of episodes by 50% or more. Patients in the active treatment group are still being followed up. This trial was registered with ClinicalTrials.gov, number NCT00605826.

Findings

278 patients were screened for inclusion, of whom 206 were randomised assigned to receive NASHA Dx (n=136) or sham treatment (n=70). 71 patients who received NASHA Dx (52%) had a 50% or more reduction in the number of incontinence episode, compared with 22 patients who received sham treatment (31%; odds ratio 2·36, 95% CI 1·24–4·47, p=0·0089). We recorded 128 treatment-related adverse events, of which two were serious (1 rectal abscess and 1 prostatic abscess).

Interpretation

Anal injection of NASHA Dx is an effective treatment for faecal incontinence. A refinement of selection criteria for patients, optimum injected dose, ideal site of injection, and long-term results might further increase the acceptance of this minimally invasive treatment.

Funding

Q-Med AB.

Introduction

Loss of the ability to defer defecation until a socially acceptable time is one of the many symptoms of faecal incontinence; other symptoms include involuntary flatus and soiling of small amounts of liquid stool to loss of solid stool and even loss of an entire bowel movement. The prevalence of faecal incontinence is the same in men and women and ranges from 2·6% in individuals aged 20–30 years to 15·3% in those older than 70 years.1 The cause of faecal incontinence is multifactorial and not completely understood. Two recognised types of clinical incontinence exist: passive incontinence and urge incontinence. Passive incontinence (ie, leakage without notice) is related to low anal resting pressure and internal sphincter deficiency. Urge incontinence (ie, inability to withstand an urge to defecate) is often attributed to an insufficiency in external sphincter tone and activity.2 Treatment depends on the presumed cause and the severity of the problem. For patients with an intact sphincter, initial treatment is usually conservative, consisting of dietary manipulation, drugs that cause constipation, and sphincter training. When such treatment does not result in satisfactory symptom relief, surgical options are considered, including anterior or posterior sphincter repair, sacral-nerve stimulation, or sphincter replacement—eg, artificial bowel sphincter implantation or stimulated graciloplasty. All these treatments have drawbacks, such as deterioration in effectiveness with time, a long learning curve for doctors (the complicated procedures are seldom done, which limits practice), high morbidity, and unreliable availability in some countries.3 In case of treatment failure, a colostomy might be the only alternative.

Injection of a biomaterial to augment a patient's anal sphincter and thereby to improve faecal continence, first described in 1993,4 is a possible treatment option. Augmentation involves expansion of tissue volume at the internal proximal part of the cylindrical sphincter complex, creating a sealing mechanism. Several different substances have been tested for use in anal injections with varying results.5 A Cochrane analysis6 concluded that because of an absence of well designed trials with an adequate number of individuals, a definite conclusion about the effectiveness of injectable substances could not be made.6 For many years, NASHA Dx (Q-Med AB, Uppsala, Sweden) has been used as a bulking agent in urological procedures, with good results and few side-effects.7 In a pilot study of NASHA Dx for treatment of faecal incontinence, the median number of incontinence episodes per week decreased from 22 to ten after 1 year, with no serious adverse events recorded.8 No randomised study of NASHA Dx has been done. The purpose of this study was to assess the efficacy and safety of injection of NASHA Dx into the submucosa of the anal sphincter in patients with faecal incontinence.

Section snippets

Patients

In this international, multicentre, randomised, double-blind, sham-controlled trial we enrolled patients with faecal incontinence from eight US centres and five European centres (all specialist tertiary referral units) between Sept 7, 2006, and Sept 12, 2008. Patients were eligible for inclusion if they were aged 18–75 years, had a Cleveland clinic Florida faecal incontinence score (CCFIS)9 of 10 or higher and at least four recorded incontinence episodes in 2 weeks, had symptoms for at least 12

Results

Of 278 patients who were screened, 206 were randomly assigned to receive either active or sham treatment (figure 1). Baseline characteristics, number of incontinence episodes, and CCFISs did not differ between groups at baseline (table 1). Baseline FIQL scores were also much the same (table 2). 112 (82%) of 136 patients in the active treatment group received retreatment and 61 (87%) of 70 in the sham group received a repeat sham procedure.

A 50% or greater reduction in the number of incontinence

Discussion

Submucosal injection of NASHA Dx provided a substantial improvement in incontinence symptoms when compared with baseline and with sham treatment. The number of incontinence episodes at 6 months in the active treatment group was reduced compared with baseline. Improvement after active treatment was satisfactory, which accords with some smaller previous studies of injectable agents to treat faecal incontinence.8, 11, 12, 13, 14 Sham treatment had an unexpected lasting positive effect on symptoms

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