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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- NTC srl
- 入组人数
- 886
- 试验地点
- 59
- 主要终点
- Phase II - Dose Finding: Proportion of Patients With Adequate Bowel Cleansing
研究概览
简要总结
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 .
详细描述
Study Start and Study Completion dates relative to the Phase II/III are reported here:
Phase II (Patients n. 183)
- Date of first enrolment: 18 June 2020
- Date LPLV: 12 November 2020
Phase III (Patients n. 703)
- Date of first enrolment: 2 March 2021
- Date LPLV: 16 July 2021
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- Single (Outcomes Assessor)
盲法说明
Endoscopist-blinded
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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).
结局指标
主要结局
Phase II - Dose Finding: Proportion of Patients With Adequate Bowel Cleansing
时间窗: During the colonoscopy procedure, carried out within 7 days of the screening visit, the evaluation is performed
Proportion of patients with adequate bowel cleansing, defined as BBPS total score ≥ 6, with a score for each of the three colon segments ≥ 2 during colonoscopy after standard washing and air insufflation for luminal distension. The mannitol dose to be used in phase III was singled out on an algorithm that calculated a total score for each dose starting from the scores assigned to the three main criteria through a ranking system and proportionally to the importance given to each main criterion: A - rate of adequate bowel cleansing (most important - primary endpoint), B - rate of patients in safe conditions and C - clinical judgement score (least important - partially based on subjective assessments).
Phase III - Non-inferiority: Proportion of Patients With Adequate Bowel Cleansing
时间窗: During the colonoscopy procedure, carried out within 7 days of the screening visit, the evaluation is performed, at least 4 hours after end of intake, following product instruction as per protocol
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 II - Dose Finding: Proportion of Patients With Adequate Bowel Cleansing
时间窗: During the colonoscopy procedure, carried out within 7 days of the screening visit, the evaluation is performed
Proportion of patients with adequate bowel cleansing, defined as BBPS total score ≥ 6, with a score for each of the three colon segments ≥ 2 during colonoscopy after standard washing and air insufflation for luminal distension. The mannitol dose to be used in phase III was singled out on an algorithm that calculated a total score for each dose starting from the scores assigned to the three main criteria through a ranking system and proportionally to the importance given to each main criterion: A - rate of adequate bowel cleansing (most important - primary endpoint), B - rate of patients in safe conditions and C - clinical judgement score (least important - partially based on subjective assessments).
Phase III - Non-inferiority: Proportion of Patients With Adequate Bowel Cleansing
时间窗: During the colonoscopy procedure, carried out within 7 days of the screening visit, the evaluation is performed, at least 4 hours after end of intake, following product instruction as per protocol
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.
次要结局
- Phase II - Dose Finding: Caecal Intubation Rate(During the colonoscopy procedure, carried out within 7 days of the screening visit, the evaluation is performed)
- Phase II - Dose Finding: Adherence to Bowel Preparation(During the colonoscopy procedure, carried out within 7 days of the screening visit, the evaluation is performed, 4 hours after the end of study drug self-administration, before colonoscopy)
- Phase II - Dose Finding: Ease of Use(During the colonoscopy procedure, carried out within 7 days of the screening visit, the evaluation is performed. 4 hours after the end of study drug self-administration, before colonoscopy (please refer to protocol))
- Phase II - Dose Finding: Willingness to Reuse the Preparation(During the colonoscopy procedure, carried out within 7 days of the screening visit, the evaluation is performed. 4 hours after the end of study drug self-administration, before colonoscopy)
- Phase II - Dose Finding: Treatment Acceptability(During the colonoscopy procedure, carried out within 7 days of the screening visit, the evaluation is performed. 4 hours after the end of study drug self-administration, before colonoscopy)
- Phase II - Pharmacokinetic Parameter: Peak Plasma Concentration(During the colonoscopy procedure, carried out within 7 days of the screening visit, the evaluation is performed. Before mannitol self-administration and 8 hours (T8) after completion of mannitol self-administration)
- Phase II - Pharmacokinetic Parameter: Time to Maximum Concentration(During the colonoscopy procedure, carried out within 7 days of the screening visit, the evaluation is performed. Before mannitol self-administration and 8 hours (T8) after completion of mannitol self-administration)
- Phase II - Pharmacokinetic Parameter: Area Under the Curve(During the colonoscopy procedure, carried out within 7 days of the screening visit, the evaluation is performed. Before mannitol self-administration and 8 hours (T8) after completion of mannitol self-administration)
- Phase II - Pharmacokinetic Parameter: Terminal Elimination Half Life(During the colonoscopy procedure, carried out within 7 days of the screening visit, the evaluation is performed. Before mannitol self-administration and 8 hours (T8) after completion of mannitol self-administration)
- Phase III - Non-inferiority: Adenoma Detection Rate(During the colonoscopy procedure, carried out within 7 days of the screening visit, the evaluation is performed)
- Phase III - Non-inferiority: Ottawa Bowel Preparation Scale (OBPS)(During the colonoscopy procedure, carried out within 7 days of the screening visit, the evaluation is performed)
- Phase III - Non-inferiority: Caecal Intubation Rate(During the colonoscopy procedure, carried out within 7 days of the screening visit, the evaluation is performed)
- Phase III - Non-inferiority: Bowel Cleansing Impact Review (BOCLIR) (Italian Sites Only)(During the colonoscopy procedure, carried out within 7 days of the screening visit, the evaluation is performed. After the end of study drug self-administration, before colonoscopy)
- Phase III - Non-inferiority: Adherence to Bowel Preparation With Mannitol and With Moviprep®.(During the colonoscopy procedure, carried out within 7 days of the screening visit, the evaluation is performed. 4 hours after the end of study drug self-administration, before colonoscopy)
- Phase III - Non-inferiority: Ease of Use(During the colonoscopy procedure, carried out within 7 days of the screening visit, the evaluation is performed. 4 hours after the end of study drug self-administration, before colonoscopy)
- Phase III - Non-inferiority: Willingness to Reuse the Preparation(During the colonoscopy procedure, carried out within 7 days of the screening visit, the evaluation is performed. 4 hours after the end of study drug self-administration, before colonoscopy)
- Phase III - Non-inferiority: Treatment Acceptability(During the colonoscopy procedure, carried out within 7 days of the screening visit, the evaluation is performed. 4 hours after the end of study drug self-administration, before colonoscopy)