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Title: | Multidonor intensive faecal microbiota transplantation for active ulcerative colitis: a randomised placebo-controlled trial | Authors: | Leong, R. W. L. Kaakoush, N. O. Walsh, A. J. Kamm, M. A. van den Bogaerde, J. Paramsothy, S. Paramsothy, R. Ng, W. Xuan, W. Connor, S. Samuel, D. Lin, E. Borody, T. J. Mitchell, H. M. |
Issue Date: | 2017 | Source: | 389, (10075), 2017, p. 1218-1228 | Pages: | 1218-1228 | Journal: | The Lancet | Abstract: | Background The intestinal microbiota is implicated in the pathogenesis of ulcerative colitis. Faecal microbiota transplantation is a novel form of therapeutic microbial manipulation, but its efficacy in ulcerative colitis is uncertain. We aimed to establish the efficacy of intensive-dosing, multidonor, faecal microbiota transplantation in active ulcerative colitis. Methods We conducted a multicentre, double-blind, randomised, placebo-controlled trial at three hospitals in Australia. We randomly allocated patients with active ulcerative colitis (Mayo score 4–10) in a 1:1 ratio, using a pre-established randomisation list, to either faecal microbiota transplantation or placebo colonoscopic infusion, followed by enemas 5 days per week for 8 weeks. Patients, treating clinicians, and other study staff were unaware of the assigned treatment. Faecal microbiota transplantation enemas were each derived from between three and seven unrelated donors. The primary outcome was steroid-free clinical remission with endoscopic remission or response (Mayo score ≤2, all subscores ≤1, and ≥1 point reduction in endoscopy subscore) at week 8. Analysis was by modified intention-to-treat and included all patients receiving one study dose. We performed 16S rRNA stool analysis to assess associated microbial changes. This trial is registered with ClinicalTrials.gov, number NCT01896635. The trial has ended; this report presents the final analysis. Findings From November, 2013, to May, 2015, 85 patients were enrolled to our trial, of whom 42 were randomly assigned faecal microbiota transplantation and 43 were allocated placebo. One patient assigned faecal microbiota transplantation and three allocated placebo did not receive study treatment and were excluded from the analysis. The primary outcome was achieved in 11 (27%) of 41 patients allocated faecal microbiota transplantation versus three (8%) of 40 who were assigned placebo (risk ratio 3·6, 95% CI 1·1–11·9; p=0·021). Adverse events were reported by 32 (78%) of 41 patients allocated faecal microbiota transplantation and 33 (83%) of 40 who were assigned placebo; most were self-limiting gastrointestinal complaints, with no significant difference in number or type of adverse events between treatment groups. Serious adverse events occurred in two patients assigned faecal microbiota transplantation and in one allocated placebo. Microbial diversity increased with and persisted after faecal microbiota transplantation. Several bacterial taxa were associated with clinical outcome; in particular, the presence of Fusobacterium spp was associated with lack of remission. Interpretation Intensive-dosing, multidonor, faecal microbiota transplantation induces clinical remission and endoscopic improvement in active ulcerative colitis and is associated with distinct microbial changes that relate to outcome. Faecal microbiota transplantation is, thus, a promising new therapeutic option for ulcerative colitis. Future work should focus on precisely defining the optimum treatment intensity and the role of donor–recipient matching based on microbial profiles. Funding Broad Medical Research Program, Gastroenterological Society of Australia, Mount Sinai (New York) SUCCESS fund, University of New South Wales.L614458767 | DOI: | 10.1016/S0140-6736(17)30182-4 | Resources: | http://linksource.ebsco.com/ls.b6e6cc08-c492-42af-aec4-c6084e18e68c.true/linking.aspx?sid=EMBASE&issn=1474547X&id=doi:10.1016%2FS0140-6736%2817%2930182-4&atitle=Multidonor+intensive+faecal+microbiota+transplantation+for+active+ulcerative+colitis%3A+a+randomised+placebo-controlled+trial&stitle=Lancet&title=The+Lancet&volume=389&issue=10075&spage=1218&epage=1228&aulast=Paramsothy&aufirst=Sudarshan&auinit=S.&aufull=Paramsothy+S.&coden=LANCA&isbn=&pages=1218-1228&date=2017&auinit1=S&auinitm= http://www.embase.com/search/results?subaction=viewrecord&from=export&id=L614458767http://dx.doi.org/10.1016/S0140-6736(17)30182-4 |
Keywords: | NCT01896635adalimumab;alanine aminotransferase;allopurinol;aspartate aminotransferase;azathioprine;bacterial DNA;biological product;budesonide;complementary DNA;corticosteroid;enema;immunomodulating agent;mercaptopurine;mesalazine;methotrexate;placebo;prednisone;probiotic agent;RNA 16S;sodium chloride;tumor necrosis factor inhibitor;abdominal pain;adult;alanine aminotransferase blood level;anemia;anus fissure;anxiety disorder;arthralgia;article;aspartate aminotransferase blood level;backache;bacterium;Bacteroides fragilis;Barnesiella;Bifidobacterium longum;biological therapy;Blautia;bloating;blurred vision;chill;clinical effectiveness;clinical outcome;Clostridium;Clostridium perfringens;colitis;colon lavage;colonoscopy;controlled study;corticosteroid therapy;coughing;depression;diarrhea;digestive system disease assessment;dizziness;Dorea;double blind procedure;drug dose reduction;drug treatment failure;dry skin;elective surgery;enterocolitis;Escherichia;Escherichia coli;Escherichia faecalis;fatigue;fecal microbiota transplantation;feces analysis;feces incontinence;feces microflora;female;fever;flatulence;flu like syndrome;foot fracture;Fusobacterium;gastroesophageal reflux;gastrointestinal symptom;genital herpes;headache;heart palpitation;hemorrhoid;human;infection complication;insomnia;intention to treat analysis;irritability;Lactobacillus casei;lip disease;lip infection;lung infection;maintenance therapy;major clinical study;male;Mayo score;microbial diversity;mouth infection;multicenter study;myalgia;nausea;nonhuman;open study;otitis media;Parabacteroides;patient safety;priority journal;quality of life;randomized controlled trial;rash;remission;Ruminococcus;sinusitis;soft tissue infection;sore throat;Sutterella;treatment response;ulcerative colitis;unrelated donors;upper respiratory tract infection;urinary tract injury;urticaria;vomiting | Type: | Article |
Appears in Sites: | Sunshine Coast HHS Publications |
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