Efficacy and Safety of mAnnitol in Bowel Preparation During Elective Colonoscopy and Comparison With Moviprep®
- Conditions
- Elective Colonoscopy
- Registration Number
- NCT04759885
- Lead Sponsor
- NTC srl
- Brief Summary
The purpose of this dose finding/comparative efficacy study is to first single out the most appropriate dose of mannitol for bowel preparation (phase II) and, subsequently, demonstrate the non-inferiority of the efficacy of single dose mannitol vs standard split 2L PEG ASC (Moviprep®) (phase III) in bowel preparation for colonoscopy .
- Detailed Description
Study Start and Study Completion dates relative to the Phase II/III are reported here:
Phase II (Patients n. 183)
* Date of first enrolment: 22 June 2020
* Date LPLV: 12 November 2020
Phase III (Patients n. 703)
* Date of first enrolment: 2 March 2021
* Date LPLV: 16 July 2021
Date on which the study was entered in the EudraCT database: 13 October 2020
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 886
- Ability of patient to consent and provide signed written informed consent
- Age ≥ 18 years
- Males and females scheduled for elective (screening, surveillance or diagnostic) colonoscopy to be prepared and performed according to the European Society of Gastrointestinal Endoscopy (ESGE) Guideline
- Patients willing and able to complete the entire study and to comply with instructions
- Pregnancy or breastfeeding. Females of childbearing potential must have a negative pregnancy test at Visit 2 and must practice one of the following methods of birth control throughout the study period (unless postmenopausal or surgically sterile, or whose sole sexual partner has had a successful vasectomy): oral, implantable, or injectable contraceptives (for a minimum of three months before study entry) in combination with a condom; intrauterine device in combination with a condom; double barrier method (condom and occlusive cap with spermicidal foam/gel/film/cream/suppository).
- Severe renal failure: glomerular filtration rate (eGFR) < 30 ml/min/1.73 m2 estimated by means of simplified MDRD equation.
- Severe heart failure: NYHA Class III-IV.
- Severe anaemia (Hb ≤ 8 g/dl).
- Severe acute and chronically active Inflammatory Bowel Disease; patients in clinical remission (Crohn's Disease Activity Index - CDAI < 150 for Crohn Disease and Partial Mayo Score ≤ 2 for Ulcerative Colitis) are allowed.
- Chronic liver disease Child-Pugh class B or C.
- Electrolyte disturbances (Na, Cl, K, Ca or P out of normal ranges).
- Recent (< 6 months) symptomatic acute ischemic heart disease.
- History of significant gastrointestinal surgeries, including colon resection, sub-total colectomy, abdominoperineal resection, de-functioning colostomy or ileostomy, Hartmann's procedure and other surgeries involving the structure and function of the colon.
- Use of laxatives, colon motility altering drugs and/or other substances (e.g. simethicone) that can affect bowel cleansing or visibility during colonoscopy within 24 hours prior to colonoscopy.
- Suspected bowel obstruction or perforation.
- Indication for partial colonoscopy.
- Patients who have received an investigational drug or therapy within 5 half-lives of the first visit.
- Patients previously screened for participation in this study.
- Hypersensitivity to the active ingredients or to any of the excipients of the study drugs.
- Contraindication to Moviprep® (only for phase III).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Primary Outcome Measures
Name Time Method Phase II - Dose finding: Proportion of patients with adequate bowel cleansing During colonoscopy (Visit 4) Proportion of patients with adequate bowel cleansing, defined as BBPS total score ≥ 6, with a score for each of the three colon segments (right; transverse, including flexures; and left, including sigmoid and rectum) ≥ 2 during colonoscopy after standard washing and air insufflation for luminal distension.
Phase III - Non-inferiority: Proportion of patients with adequate bowel cleansing During colonoscopy (Visit 4) Proportion of patients with adequate bowel cleansing, defined as BBPS total score ≥ 6, with a score for each of the three colon segments (right; transverse, including flexures; and left, including sigmoid and rectum) ≥ 2 during colonoscopy after standard washing and air insufflation for luminal distension.
- Secondary Outcome Measures
Name Time Method Phase II - Dose finding: Caecal intubation rate During colonoscopy at Visit 4 The percentage of patients with appendiceal orifice visible to the endoscopist.
Phase II - Dose finding: Adherence to bowel preparation During visit 4, 4 hours after the end of study drug self-administration, before colonoscopy Proportion of patient that completely taken, partially taken or not taken assigned mannitol dose.
Phase II - Dose finding: ease of use During visit 4, 4 hours after the end of study drug self-administration, before colonoscopy Descriptive statistics (Mean) of Numeric Rating Scale (NRS) values ranging from 0 (very difficult) to 10 (very easy).
Phase II - Dose finding: Willingness to reuse the preparation During visit 4, 4 hours after the end of study drug self-administration, before colonoscopy Proportion of patient who confirmed that they would like to reuse the preparation for other colonoscopies.
Phase II - Dose finding: Treatment acceptability During visit 4 (day of colonoscopy), 4 hours after the end of study drug self-administration, before colonoscopy Descriptive statistics (Mean) of Numeric Rating Scale (NRS) values ranging from 0 (terrible) to 10 (very good).
Phase II - Pharmacokinetic Parameter: Peak Plasma Concentration During vist 4 (day of colonoscopy), before mannitol self-administration (T0 - baseline),1 hour (T1), 2 hours (T2), 4 hours (T4) and 8 hours (T8) after completion of mannitol self-administration descriptive statistics (mean) of peak plasma concentration (Cmax) as pharmacokinetic parameter.
Phase III - Non-inferiority: Adenoma detection rate During the colonoscopy at Visit 4 The percentage of patients with at least one lesion detected.
Phase III - Non-inferiority: Adherence to bowel preparation with mannitol and with Moviprep®. During visit 4, 4 hours after the end of study drug self-administration, before colonoscopy Proportion of patients that completely taken, partially taken or not taken assigned mannitol dose
Phase III - Non-inferiority: Willingness to reuse the preparation During visit 4, 4 hours after the end of study drug self-administration, before colonoscopy Proportion of patient who confirmed that they would like to reuse the preparation for other colonoscopies.
Phase II - Pharmacokinetic Parameter: Time to Maximum Concentration During vist 4 (day of colonoscopy), before mannitol self-administration (T0 - baseline),1 hour (T1), 2 hours (T2), 4 hours (T4) and 8 hours (T8) after completion of mannitol self-administration Descriptive statistics (Median) of time to maximum concentration (tmax) as pharmacokinetic parameter.
Phase II - Pharmacokinetic Parameter: Elimination Half Life During vist 4 (day of colonoscopy), before mannitol self-administration (T0 - baseline),1 hour (T1), 2 hours (T2), 4 hours (T4) and 8 hours (T8) after completion of mannitol self-administration Descriptive statistics (Mean) of elimination half life (t1/2), as pharmacokinetic parameter.
Phase III - Non-inferiority: Ottawa Bowel Preparation Scale (OBPS) During the colonoscopy at Visit 4 Ottawa scale is used to measure the quality of the preparation in three different parts of the colon before washing and insufflation. descriptive statistics (Mean) of the total score (from 0 excellent to 14 inadequate).
Phase III - Non-inferiority: Caecal intubation rate During the colonoscopy at Visit 4 The percentage of patients with appendiceal orifice visible to the endoscopist.
Phase III - Non-inferiority: Bowel Cleansing Impact Review (BOCLIR) (Italian sites only) Visit 4 after the end of study drug self-administration, before colonoscopy The BOCLIR is a questionnaire filled in by patients to measure the acceptability and tolerability of bowel cleansers consisting of three unidimensional scales (satisfaction, symptoms and activity limitations) with good psychometric and scaling properties. Item responses are summed to provide a score for each scale and a total score. The satisfaction scale contains eight items and the score ranges from 0 (highly satisfied) to 32 (highly dissatisfied). The symptoms scale includes 14 items and the score ranges from 0 (no symptoms) to 42 (severe symptoms).
The activity limitations scale is made up of 12 items and the score ranges from 0 (no effect on activities) to 36 (activities greatly affected). The total score is the sum of the three scales and ranges from 0 to 110. Patients who report a worse experience in terms of the three factors score higher on the BOCLIR scale.Phase II - Pharmacokinetic Parameter: Area Under the Curve During vist 4 (day of colonoscopy), before mannitol self-administration (T0 - baseline),1 hour (T1), 2 hours (T2), 4 hours (T4) and 8 hours (T8) after completion of mannitol self-administration Descriptive statistics (Mean) of area under the curve from t0 to the last blood sampling time point (AUC 0-t8), as pharmacokinetic parameter.
Phase III - Non-inferiority: Treatment acceptability During visit 4, 4 hours after the end of study drug self-administration, before colonoscopy Descriptive statistics (Mean) of Numeric Rating Scale (NRS) values ranging from 0 (terrible) to 10 (very good).
Phase III - Non-inferiority: ease of use During visit 4, 4 hours after the end of study drug self-administration, before colonoscopy Descriptive statistics (Mean) of Numeric Rating Scale (NRS) values ranging from 0 (very difficult) to 10 (very easy).
Trial Locations
- Locations (35)
Centre Hospitalier Universitaire de Montpellier
🇫🇷Montpellier, France
Centre Hospitalier Henri Duffaut
🇫🇷Avignon, France
Praxis für Gastroenterologie und Fachärztliche Innere Medizin, Im Haus der Gesundheit
🇩🇪Ludwigshafen am Rhein, Germany
Hôpital Edouard Herriot
🇫🇷Lyon, France
Klinikum der Stadt Ludwigshafen
🇩🇪Ludwigshafen, Germany
Katholisches Klinikum Mainz
🇩🇪Mainz, Germany
Klinikum Worms Medizinische Klinik II
🇩🇪Worms, Germany
Fondazione Poliambulanza - Istituto Ospedaliero
🇮🇹Brescia, BR, Italy
Irkutsk State Medical Academy of Postgraduate Education
🇷🇺Irkutsk, Russian Federation
Clinical Hospital of Russian Railways N.A. Semashko
🇷🇺Moscow, Russian Federation
Moscow Clinical Research and Practical Center of the Department of Health
🇷🇺Moscow, Russian Federation
State Central Clinical Hospital A. N. Ryzhykh
🇷🇺Moscow, Russian Federation
Railway Clinical Hospital
🇷🇺Rostov, Russian Federation
Private educational organization of higher education "Medical University "Reaviz"
🇷🇺Samara, Russian Federation
Medical Center of Diagnostics and Prevention
🇷🇺Yaroslavl, Russian Federation
Regional Oncological Clinical Hospital
🇷🇺Yaroslavl, Russian Federation
Hospices civils de Lyon
🇫🇷Lyon, France
IRCCS "Saverio De Bellis"
🇮🇹Castellana Grotte, BA, Italy
ASST Rhodense - Presidi di Rho e Garbagnate
🇮🇹Garbagnate Milanese, MI, Italy
ASSL Carbonia - Presidio Ospedaliero CTO di Iglesias
🇮🇹Iglesias, CI, Italy
Ospedale Valduce
🇮🇹Como, CO, Italy
Fondazione Casa Sollievo Della Sofferenza
🇮🇹San Giovanni Rotondo, FG, Italy
Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico di Milano
🇮🇹Milano, MI, Italy
ASST Grande Ospedale Metropolitano Niguarda
🇮🇹Milano, MI, Italy
IRCCS Ospedale San Raffaele
🇮🇹Milano, MI, Italy
IRCCS Policlinico San Donato
🇮🇹San Donato Milanese, MI, Italy
Istituto Europeo di Oncologia
🇮🇹Milano, MI, Italy
Azienda Ospedaliero-Universitaria Maggiore della Carità
🇮🇹Novara, Italy
Azienda USL di Modena - Ospedale Ramazzini di Carpi
🇮🇹Carpi, MO, Italy
Azienda Ospedaliero Universitaria Pisana- Ospedale Cisanello
🇮🇹Pisa, PI, Italy
Centro di Riferimento Oncologico IRCCS
🇮🇹Aviano, PN, Italy
Policlinico Universitario A. Gemelli
🇮🇹Roma, RO, Italy
Presidio Ospedaliero Santa Chiara
🇮🇹Trento, TN, Italy
Ospedale Sacro Cuore
🇮🇹Negrar, VR, Italy
ASST Sette Laghi - Ospedale di Circolo e Fondazione Macchi
🇮🇹Varese, Italy