Dataset Information

Oral mannitol for bowel preparation: a dose-finding phase II study.

ABSTRACT:

Background

Successful bowel preparation (BP) for colonoscopy depends on the instructions, diet, the laxative product, and patient adherence, which all affect colonoscopy quality. Nevertheless, there are no laxatives which combine effectiveness, safety, easy self-administration, good patient acceptance, and low cost. However, mannitol, a sugar alcohol, could be an attractive candidate for use in clinical practice if it is shown to demonstrate adequate efficacy and safety.

Aims

The present phase II dose-finding study compared three doses of mannitol (50, 100, and 150 g) to identify the best dose to be used in a subsequent phase III study.

Methods

The Boston Bowel Preparation Scale, caecal intubation rate, adherence, acceptability, and safety profile, including measurement of potentially dangerous colonic gas concentrations (CH₄, H₂, O₂), were considered in all patients. A weighted algorithm was used to identify the best mannitol dose for use in the subsequent study.

Results

The per-protocol population included 60 patients in the 50 g group, 54 in the 100 g group, and 49 in the 150 g group. The 100 g dose was the best as it afforded optimal colon cleansing efficacy (94.4% of patients had adequate BP), adherence, acceptability, and safety, including negligible gas concentrations.

Conclusions

The present study demonstrated that the colon cleansing efficacy and safety of mannitol were dose dependent. Conversely, gas concentrations were not dose dependent and negligible in all patients. Combined evaluation of efficacy, tolerability, and safety, using a weighted algorithm, determined that mannitol 100 g was the best dose for the phase III study.

SUBMITTER: Spada C

PROVIDER: S-EPMC9649514 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Publications

Oral mannitol for bowel preparation: a dose-finding phase II study.

Spada Cristiano C Fiori Giancarla G Uebel Peter P Tontini Gian Eugenio GE Cesaro Paola P Grazioli Leonardo Minelli LM Soru Pietro P Bravi Ivana I Hinkel Carsten C Prada Alberto A Di Paolo Dhanai D Zimmermann Tim T Manes Gianpiero G Valats Jean Christophe JC Jakobs Ralf R Elli Luca L Carnovali Marino M Ciprandi Giorgio G Radaelli Franco F Vecchi Maurizio M

European journal of clinical pharmacology 20221026 12

<h4>Background</h4>Successful bowel preparation (BP) for colonoscopy depends on the instructions, diet, the laxative product, and patient adherence, which all affect colonoscopy quality. Nevertheless, there are no laxatives which combine effectiveness, safety, easy self-administration, good patient acceptance, and low cost. However, mannitol, a sugar alcohol, could be an attractive candidate for use in clinical practice if it is shown to demonstrate adequate efficacy and safety.<h4>Aims</h4>The ...[more]

PMID: 36287232

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Project description:The combination of different laxatives at reduced volumes may benefit patients by enhancing efficacy for bowel cleansing and increasing tolerability. However, evidence regarding combined preparations is scarce. This study evaluated whether the combined preparations are associated with enhanced efficacy and tolerability. This randomized phase II study had a single-blind, parallel-arm design. Between December 2013 and September 2014, consecutive patients aged between 20 and 65 years and who required diagnostic colonoscopies were considered for inclusion. Patients were randomly allocated into 4 arms: sodium picosulfate and magnesium citrate (PMC) and polyethylene glycol (PEG) with ascorbic acid in a day-prior (PMC-PEG-DP), PMC and oral sodium phosphate (NaP) in a day-prior (PMC-NaP-DP), PMC and PEG with ascorbic acid in a split-dose (PMC-PEG-SD), and PMC and oral NaP in a split-dose (PMC-NaP-SD). Primary endpoint was the Aronchick scale, and Ottawa scale results by colon segment, patients' adverse gastrointestinal symptoms, and willingness to reuse the same agents were also recorded. Successful bowel preparation was defined as an "excellent" or "good" score on the Aronchick scale. A total of 236 patients were randomized and 229 patients received the planned colonoscopy. The rates of successful bowel preparation in the PMC-PEG-DP, PMC-NaP-DP, PMC-PEG-SD, and PMC-NaP-SD were 82.5%, 64.4%, 100%, and 100%, respectively. Excluding the failed PMC-NaP-DP group, all groups showed satisfactory rates of successful bowel preparation, and the mean Ottawa scores were significantly better in the PMC-PEG-SD and PMC-NaP-SD groups than in the PMC-PEG-DP group (P < 0.0001). The PMC-PEG-DP, PMC-NaP-DP, PMC-PEG-SD, and PMC-NaP-SD groups were similar in terms of rates of adverse gastrointestinal symptoms reported on a 5-point scale (P = 0.40) and willingness to reuse the same combined preparations (P = 0.55). PMC-PEG in a day-prior or split-dose and PMC-NaP in a split-dose were efficient and tolerable bowel preparations for colonoscopy.

Project description:IntroductionEarly phase dose-finding (EPDF) studies are critical for the development of new treatments, directly influencing whether compounds or interventions can be investigated in further trials to confirm their safety and efficacy. There exists guidance for clinical trial protocols and reporting of completed trials in the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 and CONsolidated Standards Of Reporting Randomised Trials (CONSORT) 2010 statements. However, neither the original statements nor their extensions adequately cover the specific features of EPDF trials. The DEFINE (DosE-FIndiNg Extensions) study aims to enhance transparency, completeness, reproducibility and interpretation of EPDF trial protocols (SPIRIT-DEFINE) and their reports once completed (CONSORT-DEFINE), across all disease areas, building on the original SPIRIT 2013 and CONSORT 2010 statements.Methods and analysisA methodological review of published EPDF trials will be conducted to identify features and deficiencies in reporting and inform the initial generation of the candidate items. The early draft checklists will be enriched through a review of published and grey literature, real-world examples analysis, citation and reference searches and consultation with international experts, including regulators and journal editors. Development of CONSORT-DEFINE commenced in March 2021, followed by SPIRIT-DEFINE from January 2022. A modified Delphi process, involving worldwide, multidisciplinary and cross-sector key stakeholders, will be run to refine the checklists. An international consensus meeting in autumn 2022 will finalise the list of items to be included in both guidance extensions.Ethics and disseminationThis project was approved by ICR's Committee for Clinical Research. The Health Research Authority confirmed Research Ethics Approval is not required. The dissemination strategy aims to maximise guideline awareness and uptake, including but not limited to dissemination in stakeholder meetings, conferences, peer-reviewed publications and on the EQUATOR Network and DEFINE study websites.Registration detailsSPIRIT-DEFINE and CONSORT-DEFINE are registered with the EQUATOR Network.

Dataset Information

Oral mannitol for bowel preparation: a dose-finding phase II study.

Background

Aims

Methods

Results

Conclusions

Publications

Oral mannitol for bowel preparation: a dose-finding phase II study.

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