Protocol of a randomised controlled phase II clinical trial investigating PREoperative endoscopic injection of BOTulinum toxin into the sphincter of Oddi to reduce postoperative pancreatic fistula after distal pancreatectomy: the PREBOTPilot trial

IntroductionPostoperative pancreatic fistula (POPF) is still the most frequently occurring and clinically relevant complication after distal pancreatectomy (DP). Preoperative endoscopic injection of botulinum toxin (BTX) into the sphincter of Oddi represents an innovative approach to prevent POPF. The aim of this project (PREBOTPilot) is to generate the first randomised controlled trial data on the safety, feasibility and efficacy of preoperative endoscopic BTX injection into the sphincter of Oddi to prevent clinically relevant POPF following DP.Methods and analysisPREBOTPilot is an investigator-initiated, single-centre, randomised, controlled, open-label, phase II clinical trial with two parallel study groups and an exploratory study design. 60 patients scheduled for DP will be randomised to intervention and control group. In the intervention group, patients will undergo preoperative endoscopic injection of BTX into the sphincter of Oddi, whereas in the control group no preoperative endoscopy will be performed. The combined primary endpoint is the occurrence of clinically relevant POPF and/or death within 30 days after DP. The secondary endpoints comprise further postoperative outcome parameters and quality of life up to 3 months after DP as well as safety and feasibility of the procedure. Statistical analysis is based on the modified intention-to-treat population, excluding patients without status post DP. For safety analysis, rates of adverse events (AEs) and serious AEs will be calculated with 95% CIs for group comparisons.Ethics, funding and disseminationPREBOTPilot has been approved by the German Federal Institute for Drugs and Medical Devices (reference number 4043654) and the Ethics Committee of Heidelberg University (reference number AFmo-523/2019). This trial is supported by the German Federal Ministry of Education and Research (BMBF). The results of the trial will be presented at national and international conferences and published in a peer-reviewed journal.Trial registration numberDRKS00020401.

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Reproducibility of preoperative endoscopic injection of botulinum toxin into the sphincter of Oddi to prevent postoperative pancreatic fistula

Innovative Surgical Sciences ◽

10.1515/iss-2017-0040 ◽

2018 ◽

Vol 3 (1) ◽

pp. 69-75

Author(s):

Andreas Volk ◽

Marius Distler ◽

Benjamin Müssle ◽

Marco Berning ◽

Jochen Hampe ◽

...

Keyword(s):

Botulinum Toxin ◽

Pancreatic Fistula ◽

Propensity Score Analysis ◽

Surgical Complication ◽

Sphincter Of Oddi ◽

High Volume ◽

Multicenter Trial ◽

Postoperative Pancreatic Fistula ◽

Endoscopic Injection ◽

Historical Cohort

AbstractBackground:A postoperative pancreatic fistula (POPF) is the most common and potentially life-threatening surgical complication in pancreatic surgery. One possible pharmacological treatment could be the endoscopic injection of botulinum toxin (BTX) into the sphincter of Oddi to prevent POPF. Promising data reported a significantly reduced rate of clinically relevant POPF. We analyzed the effect of BTX injection in our patients undergoing distal pancreatectomy (DP).Methods:A retrospective analysis of patients undergoing DP was performed. Patients with preoperative endoscopic injection of BTX into the sphincter of Oddi were included. The end points were postoperative outcomes including POPF. BTX patients were compared with a historical cohort and matched in a 1:1 ratio using a propensity score analysis.Results:A total of 19 patients were treated with endoscopic injection of BTX before open (n=8) or laparoscopic (n=11) DP. The median age of the patients was 67 years and the mean body mass index was 25.9 kg/m2. In median, the intervention was performed 1 day (range, 0–14 days) before the operation. There were no intervention-related complications. The incidence of POPF was not statistically different between the two groups: a clinically relevant POPF grade (B/C) occurred in 32% (BTX) and 42% (control; p=0.737). Likewise, there were no significant differences in postoperative drain fluid amylase levels, morbidity, and mortality.Conclusion:The present study could not reproduce the published results of a significant lowering of grade B/C POPF. The explanations could be the timing of BTX injection before surgery and the endoscopic technique of BTX injection. However, the conflicting results after BTX injection in two high-volume centers prompt a randomized controlled multicenter trial with trained endoscopists.

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Sphincter of Oddi botulinum toxin injection to prevent pancreatic fistula after distal pancreatectomy

Surgery ◽

10.1016/j.surg.2016.09.005 ◽

2017 ◽

Vol 161 (5) ◽

pp. 1444-1450 ◽

Cited By ~ 21

Author(s):

Thilo Hackert ◽

Ulla Klaiber ◽

Ulf Hinz ◽

Tzveta Kehayova ◽

Pascal Probst ◽

...

Keyword(s):

Botulinum Toxin ◽

Pancreatic Fistula ◽

Distal Pancreatectomy ◽

Botulinum Toxin Injection ◽

Sphincter Of Oddi

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Pancreatic thickness as a predictive factor for postoperative pancreatic fistula after distal pancreatectomy using an endopath stapler

Surgery Today ◽

10.1007/s00595-012-0235-4 ◽

2012 ◽

Vol 43 (2) ◽

pp. 141-147 ◽

Cited By ~ 34

Author(s):

Keiichi Okano ◽

Minoru Oshima ◽

Keitaro Kakinoki ◽

Naoki Yamamoto ◽

Shintaro Akamoto ◽

...

Keyword(s):

Pancreatic Fistula ◽

Distal Pancreatectomy ◽

Predictive Factor ◽

Postoperative Pancreatic Fistula ◽

Pancreatic Thickness

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The control of pain due to dentin hypersensitivity in individuals with molar–incisor hypomineralisation: a protocol for a randomised controlled clinical trial

BMJ Open ◽

10.1136/bmjopen-2020-044653 ◽

2021 ◽

Vol 11 (3) ◽

pp. e044653

Author(s):

Ana Paula Taboada Sobral ◽

Elaine Marcilio Santos ◽

Ana Cecilia Aranha ◽

Paulo Vinícius Soares ◽

Caroline Moraes Moriyama ◽

...

Keyword(s):

Clinical Trial ◽

Tooth Enamel ◽

Control Group ◽

Controlled Clinical Trial ◽

Dentin Hypersensitivity ◽

Molar Incisor Hypomineralisation ◽

Randomised Controlled Clinical Trial ◽

Sensitive Teeth ◽

Randomised Controlled ◽

Incisor Hypomineralisation

IntroductionDentin hypersensitivity (DH) is defined as high sensitivity of the vital dentin when exposed to thermal, chemical or tactile stimuli. Two mechanisms are required for the occurrence of DH: (1) the dentin must be exposed and (2) the dentinal tubules must be open and connected to the pulp. Molar–incisor hypomineralisation (MIH) is a qualitative abnormality of a genetic origin that affects tooth enamel and, in most cases, is accompanied by DH. The control of tooth sensitivity is fundamental to the successful treatment of MIH. The aim of the proposed randomised, controlled, clinical trial is to evaluate the effectiveness of different protocols for the control of DH in patients with teeth affected by MIH.Methods and analysisOne hundred and forty patients who meet the inclusion criteria will be allocated to four groups. Group 1 will be the control group (placebo). In Group 2, sensitive teeth will be sealed with PermaSeal (Ultradent). In Group 3, sensitive teeth will receive low-level laser (LLL, AsGaAl) at a wavelength of 780 nm (Laser XT Therapy, DMC, São Carlos, Brazil). In Group 4, sensitive teeth will be treated with both LLL and PermaSeal (Ultradent). DH will be evaluated 15 min after the application of the treatments and the patients will be reevaluated 1 week, 1 month, 3 months and 6 months after the treatments. The primary outcome of this study is change in pain/sensitivity, when evaluated through a Visual Analogue Scale, to determine the effectiveness of the proposed treatments, as well as differences among the evaluation times for each proposed treatment.Ethics and disseminationThis protocol has been ethically approved by the local medical ethical committee (protocol number: 4.020.261). Results will be submitted to international peer-reviewed journals and presented at international conferences.Trial registration numberNCT04407702.

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