August 2014 Long-term efficacy of NASHA Dx injection therapy for treatment of fecal incontinence
A Mellgren 1, K E Matzel, J Pollack, T Hull, M Bernstein, W Graf, Nasha Dx Study Group
Abstract
Background: Injectable bulking treatment for fecal incontinence (FI) is intended to expand tissue in the anal canal and prevent fecal leakage. Use of injectable bulking agents is increasing because it can be performed in an outpatient setting and with low risk for morbidity. This study evaluated the long-term (36-month) clinical effectiveness and safety of injection of non-animal stabilized hyaluronic acid/dextranomer (NASHA Dx) on FI symptoms.
Methods: In a prospective multicenter trial, 136 patients with FI received the NASHA Dx bulking agent. Treatment success defined as a reduction in number of FI episodes by 50% or more compared with baseline (Responder50 ). Change from baseline in Cleveland Clinic Florida Fecal Incontinence Score (CCFIS) and Fecal Incontinence Quality of Life Scale (FIQL), and adverse events were also evaluated.
Key results: Successful decrease in symptoms was achieved in 52% of patients at 6 months and this was sustained at 12 months (57%) and 36 months (52%). Mean CCFIS decreased from 14 at baseline to 11 at 36 months (p < 0.001). Quality-of-life scores for all four domains improved significantly between baseline and 36 months of follow-up. Severe adverse events were rare and most adverse events were transient and pertained to minor bleeding and pain or discomfort.
Conclusions & inferences: Submucosal injection of NASHA Dx provided a significant improvement of FI symptoms in a majority of patients and this effect was stable during the course of the follow-up and maintained for 3 years.
August 2013 Efficacy and quality of life 2 years after treatment for faecal incontinence with injectable bulking agents
J Danielson 1, U Karlbom, T Wester, W Graf
Abstract
Background: Stabilized non-animal hyaluronic acid/dextranomer (NASHA Dx) gel as injectable bulking therapy has been shown to decrease symptoms of faecal incontinence, but the durability of treatment and effects and influence on quality of life (QoL) is not known. The aim of this study was to assess the effects on continence and QoL and to evaluate the relationship between QoL and efficacy up to 2 years after treatment.
Methods: Thirty-four patients (5 males, mean age 61, range 34-80) were injected with 4 × 1 ml NASHA Dx in the submucosal layer. The patients were followed for 2 years with registration of incontinence episodes, bowel function and QoL questionnaires.
Results: Twenty-six patients reported sustained improvement after 24 months. The median number of incontinence episodes before treatment was 22 and decreased to 10 at 12 months (P = 0.0004) and to 7 at 24 months (P = 0.0026). The corresponding Miller incontinence scores were 14, 11 (P = 0.0078) and 10.5 (P = 0.0003), respectively. There was a clear correlation between the decrease in the number of leak episodes and the increase in the SF-36 Physical Function score but only patients with more than 75 % improvement in the number of incontinence episodes had a significant improvement in QoL at 24 months.
Conclusions: Anorectal injection of NASHA Dx gel induces improvement of incontinence symptoms for at least 2 years. The treatment has a potential to improve QoL. A 75 % decrease in incontinence episodes may be a more accurate threshold to indicate a successful incontinence treatment than the more commonly used 50 %.
May 2013 Long-term efficacy of dextranomer in stabilized hyaluronic acid (NASHA/Dx) for treatment of faecal incontinence
F La Torre 1, F de la Portilla
Abstract
Aim: Randomized, controlled trials have demonstrated the efficacy and safety of injectable bulking agents for the treatment of faecal incontinence (FI), although the long-term outcome has not been assessed. NASHA/Dx gel, a biocompatible, nonallergenic bulking agent consisting of nonanimal stabilized hyaluronic acid and dextranomer microspheres, has demonstrated efficacy and safety for up to 12 months after treatment. The objective of this study was to evaluate the long-term efficacy and safety of NASHA/Dx, assessed 24 months after treatment.
Method: This study was a 24-month follow-up assessment of patients treated with NASHA/Dx under open-label conditions. Data on FI episodes and quality of life measures were collected from diaries over the 28-day period immediately preceding the 24-month assessment. Adverse events were collected.
Results: Eighty-three of 115 patients completed the 24-month follow-up assessment. At 24 months, 62.7% of patients were considered responders and experienced a ≥ 50% reduction in the total number of FI episodes. The median number of FI episodes declined by 68.8% (P < 0.001). Episodes of both solid and liquid stool incontinence decreased. The mean number of incontinence-free days increased from 14.6 at baseline to 21.7 at 24 months (P < 0.001). Incontinence scores and FI quality of life scores also showed significant improvements. The most common adverse events (AEs) were proctalgia (13.3%) and pyrexia (9.6%). The majority of AEs were mild to moderate, self-limited and resolved within 1 month of the injection.
Conclusion: NASHA/Dx is safe, effective and durable over a 24-month period with a majority of patients experiencing significant improvement in multiple symptoms associated with FI.
March 2011 Efficacy of dextranomer in stabilised hyaluronic acid for treatment of faecal incontinence: a randomised, sham-controlled trial
Wilhelm Graf1, Anders Mellgren, Klaus E Matzel, Tracy Hull, Claes Johansson, Mitch Bernstein, NASHA Dx Study Group
Abstract
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.
August 2012 Dextranomer in stabilized sodium hyaluronate (Solesta®): in adults with faecal incontinence
Abstract
Dextranomer in stabilized sodium hyaluronate, hereafter referred to as dextranomer/hyaluronic acid, is a biocompatible bulking agent administered by submucosal injection. It is hypothesized to expand the submucosal layer of the proximal anal canal, thereby augmenting bowel control. Treatment with dextranomer/hyaluronic acid was associated with symptomatic improvements in adult patients with faecal incontinence participating in a randomized, double-blind, sham-controlled, multinational study and a noncomparative, multinational study. In the double-blind study, patients in the dextranomer/hyaluronic acid group met the primary efficacy objective in that a significantly higher proportion of patients responded to treatment (≥50% reduction from baseline in the number of incontinence episodes) at the 6-month post-treatment timepoint than in the sham group (two of three primary response criteria), with the durability of the treatment response (≥25% reduction from baseline in the number of incontinence episodes) confirmed at the 12-month post-treatment timepoint (third primary response criterion). For the most part, dextranomer/hyaluronic acid did not significantly differ from the sham treatment in terms of quality of life and various other symptomatic endpoints at 6 months post-treatment in the double-blind study, although there were significant improvements from baseline in various parameters, such as the mean number of incontinence-free days, the median number of incontinence episodes and mean Faecal Incontinence Quality of Life domain scores, at 12 months post-treatment. In general, dextranomer/hyaluronic acid was well tolerated for up to 18 months post-treatment, with the majority of treatment-related adverse events considered mild or moderate in intensity.