Clinical Trial on Bowel Preparation Comparing Mannitol 100g to Plenvu Both in a Same Day Regimen (CLEARWAY) (CLEARWAY)

A Phase III, International, Multicenter, Randomized, Parallel-group, Endoscopist-blinded Non-inferiority Study of the Efficacy, Safety and Patient Acceptance of Mannitol Versus Plenvu® in Bowel Preparation for Elective Colonoscopy. CLEARWAY

This is a study to test the non-inferiority of bowel cleansing with 100 g Mannitol against standard Plenvu® same-day dosing regimen. The 50% of the subjects will receive Mannitol, while the remaining part will receive Plenvu®.

Study Overview

• Status: Recruiting
• Conditions: Elective Colonoscopy
• Intervention / Treatment: Drug: 100g of Mannitol; Drug: 1L PEG-Asc

Detailed Description

Not provided

• Study Type: Interventional
• Enrollment (Estimated): 412
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Alessandro Colombo; Phone Number: +393512044335; Email: alessandro.colombo@ntcpharma.com

Study Locations

• Belgium
  • Anderlecht, Belgium, 1070
    • Recruiting
    • Hôpital Erasme
    • Contact: Arnaud Lemmers, Prof.
  • Leuven, Belgium, 3000
    • Recruiting
    • Katholieke Universiteit te Leuven
    • Contact: Raf Bisschops, Prof.
  • Ostend, Belgium, 8400
    • Recruiting
    • Algemeen Ziekenhuis Damiaan Oostende
    • Contact: Pieter DeWint, Prof.
• Italy
  • Bologna, Italy, 40138
    • Recruiting
    • Azienda Ospedaliero-Universitaria di Bologna IRCCS Istituto di Ricerca e di Cura a Carattere Scientifico
    • Contact: Lorenzo Fuccio, Dr.
  • Brescia, Italy, 25124
    • Recruiting
    • Fondazione Poliambulanza
    • Contact: Paola Cesaro, Dr.
  • Como, Italy, 22100
    • Recruiting
    • Congregazione Delle Suore Infermiere Dell'Addolorata - Ospedale Valduce
    • Contact: Franco Radaelli, Dr.
  • Milan, Italy, 20141
    • Recruiting
    • Istituto Europeo Di Oncologia
    • Contact: Giuseppe De Roberto, Dr.
  • Milan, Italy, 20122
    • Recruiting
    • Fondazione IRCCS Cà Granda Ospedale Policlinico
    • Contact: Gian Eugenio Tontini, Prof.
  • Roma, Italy, 00168
    • Recruiting
    • Policlinico Universitario A. Gemelli
    • Contact: Cristiano Spada, Prof.
  • Trento, Italy, 38122
    • Recruiting
    • Azienda Provinciale Per I Servizi Sanitari
    • Contact: Armando Gabbrielli, Dr.
  • Modena
    • Carpi, Modena, Italy, 41012
      • Recruiting
      • Azienda Unita Sanitaria Locale Di Modena - Ospedale Ramazzini di Carpi
      • Contact: Mauro Manno, Dr.
  • Pordenone
    • Aviano, Pordenone, Italy, 33081
      • Recruiting
      • Centro di Riferimento Oncologico di Aviano
      • Contact: Renato Cannizzaro, Prof.
  • Verona
    • Negrar, Verona, Italy, 37024
      • Recruiting
      • IRCCS Ospedale Sacro Cuore Don Calabria
      • Contact: Paolo Bocus, Dr.
• Poland
  • Tychy, Poland, 43-100
    • Recruiting
    • H-T.Centrum Medyczne Sp. z o.o. sp.k.
    • Contact: Marcin Romanczyk, Dr.
  • Warsaw, Poland, 02-781
    • Recruiting
    • Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy
    • Contact: Michal Filip Kaminski, Prof.
  • Warsaw, Poland, 02-665
    • Active, not recruiting
    • Klinika Reuma Park Sp. z o.o. S.K.
• Spain
  • Barcelona, Spain, 08036
    • Recruiting
    • Hospital Clinic De Barcelona
    • Contact: Maria Pellise Urquiza, Dr.
• Sweden
  • Örebro, Sweden, 701 85
    • Recruiting
    • Region Oerebro Laen
    • Contact: Nills Nyhlin, Prof.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Ability of subject to consent and provide signed written informed consent.
2. Age ≥ 18 years.
3. Males and females scheduled for elective colonoscopy performed according to ESGE guidelines.
4. Subjects willing and able to complete the entire study and to comply with instructions.

Exclusion Criteria:

1. Pregnancy or breast feeding. Females of childbearing potential must have a negative pregnancy test at Visit 2 and practice highly effective methods of birth control throughout the study period, according to the CTCG "Recommendations related to contraception and pregnancy testing in clinical trials" v 1.2* (unless postmenopausal or surgically sterile, or whose sole sexual partner had a successful vasectomy).
2. Severe acute and chronically active inflammatory bowel disease; subjects in clinical remission (Crohn's Disease Activity Index - CDAI < 150 for Crohn Disease (Best et al. 1976) and Partial Mayo Score ≤ 2 for Ulcerative Colitis (Schroeder et al. 1987)) are allowed.
3. Severe renal failure: eGFR < 30 ml/min/1.73 m2 estimated by simplified MDRD equation.
4. Severe heart failure: New York Heart Association (NYHA) Class III-IV.
5. Severe anaemia (Hb ≤ 8 g/dl).
6. Chronic liver disease Child-Pugh class B or C.
7. Electrolyte disturbances (baseline values of Na2+, Cl-, K+ out of normal ranges).
8. Clinically significant alterations of baseline haemato-chemical parameters.
9. Recent (< 6 months) symptomatic acute ischemic heart disease.
10. 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.
11. History of paralysis of the gut (ileus).
12. History of disorders of gastric emptying (e.g. gastroparesis, gastric retention, etc.).
13. History of phenylketonuria (due to presence of aspartame).
14. History of glucose-6-phosphate dehydrogenase deficiency (due to presence of ascorbate).
15. History of toxic megacolon.
16. Use within 24 hours prior to colonoscopy of laxatives, colon motility altering drugs and/or other substances (e.g., simethicone) that could affect bowel cleansing or visibility during colonoscopy.
17. Suspected bowel obstruction or perforation.
18. Indication for partial colonoscopy.
19. Subjects who received an investigational drug or therapy within 5 half-lives of the first visit.
20. Hypersensitivity to the active ingredients or to any of the excipients of the study drugs.
21. Underwater colonoscopy instead of standard gas insufflation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Test arm; One day single dose preparation same day of colonoscopy	Drug: 100g of Mannitol; Participants should self administer the preparation within 45 minutes, dissolving 100g of powder in 1L of water
Active Comparator: 1L PEG-Asc; Two liters of overall preparation, taken according to split-dose regimen the same day of colonoscopy	Drug: 1L PEG-Asc; Self administration of the same day preparation according to the on lable instruction for use. The first dose consists in dissolving Dose 1 in 500ml of water, followed by another 500ml of water, all within 1 hour. After a 1 hour wait from the end of the first dose, the participant should self administer the Dose 2 consisting in dissolving one sachetA and one sachetB in 500ml of water, followed by another 500ml of water; all within 1 hour.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of subjects with adequate bowel cleansing defined by the Boston Bowel Preparation Scale (BBPS) total score	Proportion of subjects 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 after standard washing and air or CO2 insufflation for luminal distension.	During colonoscopy (visit4), maximum 28 days after signing the informed consent form)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adenoma detection rate	Adenoma detection rate, defined as the proportion of subjects ≥ 50 years old undergoing colonoscopy who have at least one lesion detected.	During colonoscopy (visit4), maximum 28 days after signing the informed consent form)
Caecal intubation rate	Caecal intubation rate, defined as the proportion of subjects undergoing colonoscopy with ileocecal junction appendiceal orifice visible to the endoscopist.	During colonoscopy (visit4), maximum 28 days after signing the informed consent form)
Proportion of subjects undergoing colonoscopy who have to repeat the procedure	Proportion of subjects undergoing colonoscopy who have to repeat the procedure due to inadequate intestinal cleansing to resolve, at the discretion of the endoscopist, the clinical issue underlying the request for colonoscopy.	During colonoscopy (visit4), maximum 28 days after signing the informed consent form)
Proportion of subjects undergoing colonoscopy with presence of colonic bubbles	Proportion of subjects undergoing colonoscopy with presence of colonic bubbles assessed through the Colon Endoscopic Bubble Scale (CEBuS).	During colonoscopy (visit4), maximum 28 days after signing the informed consent form)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory Efficacy	Number, appearance, size, location, and histological examination of neoplastic and inflammatory colorectal lesions.	During colonoscopy (visit4), maximum 28 days after signing the informed consent form)
Adherence	Adherence: study drug completely taken, partially taken, not taken.	During colonoscopy (visit4), maximum 28 days after signing the informed consent form, after completing the preparation but before colonoscopy
Ease of use	Ease of use: numeric rating scale (NRS) (0 = very difficult to 10 = very easy).	During colonoscopy (visit4), maximum 28 days after signing the informed consent form, after completing the preparation but before colonoscopy
Taste	Taste: NRS (0 = terrible to 10 = very good).	During colonoscopy (visit4), maximum 28 days after signing the informed consent form, after completing the preparation but before colonoscopy
Willingness to reuse the preparation	Willingness to reuse the preparation (yes/no).	During colonoscopy (visit4), maximum 28 days after signing the informed consent form, after completing the preparation but before colonoscopy
Satisfaction with bowel preparation compared to cleansing agent used for previous colonoscopy.	Satisfaction with bowel preparation compared to cleansing agent used for previous colonoscopy.	During colonoscopy (visit4), maximum 28 days after signing the informed consent form, after completing the preparation but before colonoscopy
Incidence of adverse events	Incidence of adverse events starting from the beginning of study drug administration.	From signature of the informed consent form up to and including V5, maximum 29 days after signing the informed consent form
Incidence of drug-related adverse events	Incidence of drug-related adverse events starting from the beginning of study drug self-administration	From signature of the informed consent form up to and including V5, maximum 29 days after signing the informed consent form
Proportion of subjects with clinically significant change from baseline of haematological and chemical parameters	Proportion of subjects with clinically significant change from baseline of haematological and chemical parameters 4 hours and 8 hours after completion of study drug self-administration, where clinically significant means that in the Investigator's opinion the change needs an additional control or a medical intervention.	At visit 2 (maximum 21 days after signing the informed consent form) and V4 (maximum 28 days after signing the informed consent form)
Proportion of subjects with clinically significant change from baseline of heart rate, systolic and diastolic blood	Proportion of subjects with clinically significant change from baseline of heart rate, systolic and diastolic blood pressure measured from the beginning of study drug self-administration to the end of study, as well as clinically significant change of oxygen saturation during colonoscopy, where clinically significant means that in the Investigator's opinion the change needs an additional control or a medical intervention.	At visit 2 (maximum 21 days after signing the informed consent form) and V4 (maximum 28 days after signing the informed consent form)
PK sub-study: Cmax	Maximum Peak Plasma Concentration observed concentration (Cmax).	During colonoscopy (visit4), maximum 28 days after signing the informed consent form
PK sub-study: tmax	Time to maximum observed concentration (tmax).	During colonoscopy (visit4), maximum 28 days after signing the informed consent form
PK sub-study: AUC0-t or AUClast	Area under concentration-time curve, from 0 to the last blood sampling time point with measurable concentration (i.e., the last quantifiable timepoint) (AUC0-t or AUClast).	During colonoscopy (visit4), maximum 28 days after signing the informed consent form
PK sub-study: t1/2	Elimination half-life (t1/2).	During colonoscopy (visit4), maximum 28 days after signing the informed consent form

Collaborators and Investigators

• Sponsor: NTC srl
• Investigators: Study Chair: Cristiano Spada, Prof., Policlinico Universitario A. Gemelli

Study record dates

Study Major Dates

• Study Start (Actual): September 2, 2025
• Primary Completion (Estimated): March 31, 2026
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: March 6, 2026
• First Submitted That Met QC Criteria: March 6, 2026
• First Posted (Actual): March 12, 2026

Study Record Updates

• Last Update Posted (Actual): March 13, 2026
• Last Update Submitted That Met QC Criteria: March 11, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Colonoscopy preparation; Bowel cleansing; Mannitol
• Additional Relevant MeSH Terms: Organic Chemicals; Carbohydrates; Alcohols; Sugar Alcohols; Mannitol
• Other Study ID Numbers: Mannitol_01-2024

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No