Clinical trial NCT04759885: Efficacy and Safety of mAnnitol in Bowel Preparation During Elective Colonoscopy and Comparison With Moviprep®
Official title: Efficacy and Safety of mAnniTol in Bowel Preparation: Assessment of Adequacy and Presence of Intestinal levelS of Hydrogen and Methane During Elective Colonoscopy aFter mAnnitol or Standard Split 2-liter Polyethylene Glycol Solution Plus asCorbaTe - a Phase II/III, International, Multicentre, Randomized, Parallel-group, endoscOpist-bliNded, Dose-finding/Non-inferiority Study - SATISFACTION
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Elective Colonoscopy
Keywords: Colonoscopy preparation
Bowel cleansing
Gas
Mannitol
Lead sponsor: NTC srl
Sponsor class: INDUSTRY
First posted: 2021-02-18
Enrollment: 886
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A randomized, parallel-group study.
Primary purpose: DIAGNOSTIC

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

Eligibility criteria: Inclusion Criteria:

1. Ability of patient to consent and provide signed written informed consent
2. Age ≥ 18 years
3. 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
4. Patients willing and able to complete the entire study and to comply with instructions

Exclusion Criteria:

1. 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).
2. Severe renal failure: glomerular filtration rate (eGFR) \< 30 ml/min/1.73 m2 estimated by means of simplified MDRD equation.
3. Severe heart failure: NYHA Class III-IV.
4. Severe anaemia (Hb ≤ 8 g/dl).
5. 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.
6. Chronic liver disease Child-Pugh class B or C.
7. Electrolyte disturbances (Na, Cl, K, Ca or P out of normal ranges).
8. Recent (\< 6 months) symptomatic acute ischemic heart disease.
9. 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.
10. 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.
11. Suspected bowel obstruction or perforation.
12. Indication for partial colonoscopy.
13. Patients who have received an investigational drug or therapy within 5 half-lives of the first visit.
14. Patients previously screened for participation in this study.
15. Hypersensitivity to the active ingredients or to any of the excipients of the study drugs.
16. Contraindication to Moviprep® (only for phase III).

Primary outcomes:
measure: Phase II - Dose finding: Proportion of patients with adequate bowel cleansing
timeFrame: During colonoscopy (Visit 4)
measure: Phase III - Non-inferiority: Proportion of patients with adequate bowel cleansing
timeFrame: During colonoscopy (Visit 4)
Secondary outcomes:
measure: Phase II - Dose finding: Caecal intubation rate
timeFrame: During colonoscopy at Visit 4
measure: Phase II - Dose finding: Adherence to bowel preparation
timeFrame: During visit 4, 4 hours after the end of study drug self-administration, before colonoscopy
measure: Phase II - Dose finding: ease of use
timeFrame: During visit 4, 4 hours after the end of study drug self-administration, before colonoscopy
measure: Phase II - Dose finding: Willingness to reuse the preparation
timeFrame: During visit 4, 4 hours after the end of study drug self-administration, before colonoscopy
measure: Phase II - Dose finding: Treatment acceptability
timeFrame: During visit 4 (day of colonoscopy), 4 hours after the end of study drug self-administration, before colonoscopy
measure: Phase II - Pharmacokinetic Parameter: Peak Plasma Concentration
timeFrame: 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
measure: Phase II - Pharmacokinetic Parameter: Time to Maximum Concentration
timeFrame: 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
measure: Phase II - Pharmacokinetic Parameter: Area Under the Curve
timeFrame: 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
measure: Phase II - Pharmacokinetic Parameter: Elimination Half Life
timeFrame: 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
measure: Phase III - Non-inferiority: Adenoma detection rate
timeFrame: During the colonoscopy at Visit 4
measure: Phase III - Non-inferiority: Ottawa Bowel Preparation Scale (OBPS)
timeFrame: During the colonoscopy at Visit 4
measure: Phase III - Non-inferiority: Caecal intubation rate
timeFrame: During the colonoscopy at Visit 4
measure: Phase III - Non-inferiority: Bowel Cleansing Impact Review (BOCLIR) (Italian sites only)
timeFrame: Visit 4 after the end of study drug self-administration, before colonoscopy
measure: Phase III - Non-inferiority: Adherence to bowel preparation with mannitol and with Moviprep®.
timeFrame: During visit 4, 4 hours after the end of study drug self-administration, before colonoscopy
measure: Phase III - Non-inferiority: ease of use
timeFrame: During visit 4, 4 hours after the end of study drug self-administration, before colonoscopy
measure: Phase III - Non-inferiority: Willingness to reuse the preparation
timeFrame: During visit 4, 4 hours after the end of study drug self-administration, before colonoscopy
measure: Phase III - Non-inferiority: Treatment acceptability
timeFrame: During visit 4, 4 hours after the end of study drug self-administration, before colonoscopy
Other outcomes:
measure: Phase II - Dose finding: Patients in safe condition related to potentially critical concentrations of gases (H2/CH4)
timeFrame: During colonoscopy after standard washing and air insufflation for luminal distension at Visit 4
measure: Phase II - Dose finding: Incidence of adverse events
timeFrame: Visit 2 (≤ 7 days before Visit 4), Visit 3 (≤ 7 days before Visit 4) and Visit 4 (day of colonoscopy)
measure: Phase II - Dose finding: Proportion of patients with clinically significant change of haematological and chemical parameters from baseline
timeFrame: During visit 4 (day of colonoscopy), 4 hours and 8 hours after completion of study drug self administration
measure: Phase II - Dose finding: Proportion of patients with clinically significant change of vital signs during colonoscopy
timeFrame: During the colonoscopy at Visit 4
measure: Phase III - Dose finding:Patients in safe condition related to potentially critical concentration of gases (H2/CH4)
timeFrame: During the colonoscopy at Visit 4
measure: Phase III - Non-inferiority: Incidence of adverse events
timeFrame: Visit 2 (≤ 7 days before Visit 4), Visit 3 (≤ 7 days before Visit 4) and Visit 4 (day of colonoscopy)
measure: Phase III - Non-inferiority: Proportion of patients with clinically significant change of haematological and chemical parameters from baseline
timeFrame: During visit 4 (day of colonoscopy), 4 hours and 8 hours after completion of study drug self-administration
measure: Phase III - Non-inferiority: Proportion of patients with change of vital signs from baseline and during colonoscopy
timeFrame: Visit 4 prior to colonoscopy
Locations:
city: Avignon
country: France
facility: Centre Hospitalier Henri Duffaut
city: Lyon
country: France
facility: Hospices civils de Lyon
city: Lyon
country: France
facility: Hôpital Edouard Herriot
city: Montpellier
country: France
facility: Centre Hospitalier Universitaire de Montpellier
city: Ludwigshafen am Rhein
country: Germany
facility: Praxis für Gastroenterologie und Fachärztliche Innere Medizin, Im Haus der Gesundheit
city: Ludwigshafen
country: Germany
facility: Klinikum der Stadt Ludwigshafen
city: Mainz
country: Germany
facility: Katholisches Klinikum Mainz
city: Worms
country: Germany
facility: Klinikum Worms Medizinische Klinik II
city: Castellana Grotte
country: Italy
facility: IRCCS "Saverio De Bellis"
state: BA
city: Brescia
country: Italy
facility: Fondazione Poliambulanza - Istituto Ospedaliero
state: BR
city: Iglesias
country: Italy
facility: ASSL Carbonia - Presidio Ospedaliero CTO di Iglesias
state: CI
city: Como
country: Italy
facility: Ospedale Valduce
state: CO
city: San Giovanni Rotondo
country: Italy
facility: Fondazione Casa Sollievo Della Sofferenza
state: FG
city: Garbagnate Milanese
country: Italy
facility: ASST Rhodense - Presidi di Rho e Garbagnate
state: MI
city: Milano
country: Italy
facility: Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico di Milano
state: MI
city: Milano
country: Italy
facility: ASST Grande Ospedale Metropolitano Niguarda
state: MI
city: Milano
country: Italy
facility: IRCCS Ospedale San Raffaele
state: MI
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia
state: MI
city: San Donato Milanese
country: Italy
facility: IRCCS Policlinico San Donato
state: MI
city: Carpi
country: Italy
facility: Azienda USL di Modena - Ospedale Ramazzini di Carpi
state: MO
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana- Ospedale Cisanello
state: PI
city: Aviano
country: Italy
facility: Centro di Riferimento Oncologico IRCCS
state: PN
city: Roma
country: Italy
facility: Policlinico Universitario A. Gemelli
state: RO
city: Trento
country: Italy
facility: Presidio Ospedaliero Santa Chiara
state: TN
city: Negrar
country: Italy
facility: Ospedale Sacro Cuore
state: VR
city: Novara
country: Italy
facility: Azienda Ospedaliero-Universitaria Maggiore della Carità
city: Varese
country: Italy
facility: ASST Sette Laghi - Ospedale di Circolo e Fondazione Macchi
city: Irkutsk
country: Russian Federation
facility: Irkutsk State Medical Academy of Postgraduate Education
city: Moscow
country: Russian Federation
facility: Clinical Hospital of Russian Railways N.A. Semashko
city: Moscow
country: Russian Federation
facility: Moscow Clinical Research and Practical Center of the Department of Health
city: Moscow
country: Russian Federation
facility: State Central Clinical Hospital A. N. Ryzhykh
city: Rostov
country: Russian Federation
facility: Railway Clinical Hospital
city: Samara
country: Russian Federation
facility: Private educational organization of higher education "Medical University "Reaviz"
city: Yaroslavl
country: Russian Federation
facility: Medical Center of Diagnostics and Prevention
city: Yaroslavl
country: Russian Federation
facility: Regional Oncological Clinical Hospital
Study officials:
affiliation: ASST Rhodense - Presidi di Rho e Garbagnate
name: Gianpiero Manes, Dr.
role: PRINCIPAL_INVESTIGATOR
References: