Efficacy and safety of PICOPREP tailored dosing compared with PICOPREP day-before dosing for colon cleansing: a multi-centric randomised study

Ralf Kiesslich, Stefan Schubert, Michael Mross, Tobias Klugmann, Michael Klemt-Kropp, Imke Behnken, Gillaume Bonnaud, Eric Keulen, Marcel Groenen, Michael Blaker, Thierry Ponchon, Wilfred Landry, Meredin Stoltenberg, Ralf Kiesslich, Stefan Schubert, Michael Mross, Tobias Klugmann, Michael Klemt-Kropp, Imke Behnken, Gillaume Bonnaud, Eric Keulen, Marcel Groenen, Michael Blaker, Thierry Ponchon, Wilfred Landry, Meredin Stoltenberg

Abstract

Background and study aims The success of any colonoscopy procedure depends upon the quality of bowel preparation. We evaluated the efficacy and safety of a new tailored dosing (TD) regimen compared with the approved PICOPREP day-before dosing regimen (DBD) in the European Union. Patient and methods Patients (≥ 18 years) undergoing colonoscopy were randomised (2:1) to TD (Dose 1, 10 - 18 hours; Dose 2, 4 - 6 hours before colonoscopy) or DBD (Dose 1 before 8:00AM on the day before colonoscopy; Dose 2, 6 - 8 hours after Dose 1). The primary endpoint of overall colon cleansing efficacy was based on total Ottawa Scale (OS) scores (0 - 14, excellent-worst). The key secondary endpoint was a binary endpoint based on the ascending colon OS (success 0 or 1, failure [≥ 2]). Convenience and satisfaction were evaluated similar to the primary and key secondary endpoints. Safety and tolerability were also evaluated. Results Use of the PICOPREP TD regimen resulted in a statistically significant reduction in the mean total Ottawa Scale score compared to the PICOPREP DBD regimen (-3.93, 95 % confidence intervals [CI]: - 4.99, - 2.97; P < 0.0001) in the intent-to-treat analysis set. The PICOPREP TD regimen also resulted in a statistically significant increase in the odds of achieving an ascending colon OS score ≤ 1, compared to the PICOPREP DBD regimen (estimated odds ratio 9.18, 95 % CI: 4.36, 19.32; P < 0.0001). There was no statistically significant difference in the overall rate of treatment-emergent adverse events (12 % (TD) and 5.7 % (DBD), respectively, P = 0.2988). The convenience and satisfaction were comparable in the two groups. Conclusion The TD regimen was superior to the DBD regimen for overall and ascending colon cleansing efficacy. ClinicalTrials.gov Identifier: NCT02239692.

Conflict of interest statement

Competing interests Ralf Kiesslich has received research support and speaker fee from Ferring pharmaceuticals. Stefan Schubert has received grants from Ferring pharmaceuticals for travel and meetings for this study. Michael Klemt-Kropp has received grants from Gilead Siences for an observational study “Retrieval of patients chronically infected with Hep. B and C in Northern Holland”. He has also received fees from AbbVie as a consulting member of international advisory Board hepatitis C. Furthermore, he has received fees for lectures, presentations and for moderating medical events on hepatitis B and C. Imke Behnken has received payments for lectures including service on speaker’s bureaus from MSD, Astra Zeneca and Novartis. Gillaume Bonnaud has received consulting fees/honarium from Ferring pharmaceuticals, Abbvie, Aptacis, MSD, Covidien and Takeda. He has also received travel allowance for the meetings and manuscript preparation and fees for participation in review activities such as data monitoring boards. Michael Blaker has received payments for lectures and chairs at symposia and conventions from Ferring Pharmaceuticals. Thierry Ponchon has received grants from Boston Scientific, Cook and Olympus Co. He has received consulting fees or honorium from Olympus Co, Boston Scientific, Cook Medical and Mayloy Spindler. He has also received fees for participation in review activities from Norgine and payments for lectures including service on speaker bureaus from Olympus Co, Boston Scientific, Cook Medical Fujifilm and Covidien. Michael Mross, Tobias Klugmann, Eric Keulen, Marcel Groenen and Wilfred Landry have no conflict of interests to disclose. Meredin Stoltenberg is an employee of Ferring pharmaceuticals.

Figures

Fig. 1
Fig. 1
CONSORT flow diagram.As-Treated-ITT analysis set comprised of patients in the ITT analysis set who received the planned treatment, and excluded were the patients who were not treated.ITT, intention-to-treat; PP, per-protocol
Fig. 2
Fig. 2
Difference in total Ottawa Scale scores between the tailored dosing and the day-before dosing regimens (ITT, PP and completer analysis set).Lower Ottawa Scale scores correspond to better colon cleansing efficacy.DBD, day-before dosing; ITT, intention-to-treat; PP, per-protocol; TD, tailored dosing
Fig. 3
Fig. 3
Responder status of tailored dosing and day-before dosing regimens (ITT population).DBD, day-before dosing; ITT, intention-to-treat; TD, tailored dosing
Appendix
Appendix
Patient Questionnaire.

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