Effects of a Peripherally Acting µ-opioid Receptor Antagonist on Recurrent Acute Pancreatitis An Investigator-initiated, Randomized, Placebo-controlled, Double-blind Clinical Trial
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 74
- 试验地点
- 5
- 主要终点
- Number of AP attacks verified by the Atlanta Criteria
研究概览
简要总结
This study will investigate the effect of a peripheral acting opioid antagonist (PAMORA) on the disease course of patients with recurrent acute inflammation of the pancreas (acute pancreatitis). The study will be conducted by treating outpatients suffering from recurrent acute pancreatitis with a PAMORA (naldemedine) for 12 months.
详细描述
In this study, the effects of a peripheral acting µ-opioid receptor antagonist (PAMORA) on disease recurrence and progression in patients with recurrent acute pancreatitis (RAP) will be investigated. Patients with RAP will be administered 0,2 mg naldemedine orally daily or matching placebo. This medication is defined as the investigational product. Naldemedine is approved by the European Medical Agency for treatment of opioid-induced constipation. This PAMORA have not previously been investigated in patients with pancreatitis. The dose regimes for this study will be according to label. It has previously been shown, in patients with opioid-induced obstipation and healthy subjects, that opioid antagonism incl. PAMORA treatment increases gut motility, relaxes gastrointestinal sphincters, increases the intestinal water content and improves the immune response, without affecting analgesia. The affinity of PAMORAs to the µ-opioid receptors is much stronger than opioid analgesics. Therefore, they as antagonists have the potential to counteract the harmful effects of opioids on the gut mucosa, bacterial translocation and inflammation despite the high levels of exogenous opioids present in patients with pancreatitis. PAMORAs do not cross the blood-brain barrier and consequently do not interfere with analgesia or other central effects of opioids.
It is hypothesized that treatment with the PAMORA naldemedine will antagonize the harmful effects of opioids without reducing analgesia in patients with RAP and hence reduce disease severity and improve clinical outcomes. If successful, this study will for the first time document the effects of a targeted pharmacotherapy in RAP with the potential benefit of improved patient outcomes.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 74 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent before any study specific procedures
- •Able to read and understand Danish or Swedish (depending on site)
- •Male or female age between 18 and 74 years
- •At least one attack of non-biliary AP (as defined by the revised Atlanta criteria) within the last 12 months and at least two attacks within 5 years
- •Clinically stable at time of inclusion
- •The researcher believes that the participant understands what the study entails, is capable of following instructions, can attend when needed, and is expected to complete the study
- •The investigator will ensure that fertile female participants have a negative pregnancy test before treatment initiation and use contraception during the study period. The following methods of contraception, if properly used, are generally considered reliable: oral contraceptives, patch contraceptives, injection contraceptives, vaginal contraceptive ring, intrauterine device, surgical sterilization (bilateral tubal ligation), vasectomized partner, double barrier (condom and pessary), or sexual abstinence. Methods of contraception will be documented in the source documents
排除标准
- •Known allergy towards study medication
- •Known or suspected major stenosis or perforation of the intestines
- •Known or suspected abdominal cancer (incl. intestine, pancreas and the biliary tree)
- •Pre-existing renal insufficiency (defined as habitual eGFR below 45)
- •Female participants that are lactating
- •Severe pre-existing comorbidities (assessed by investigator upon inclusion)
- •Attack of AP requiring admission within two weeks prior to inclusion
- •Gallstone etiology of RAP (MRCP or endoscopic ultrasound excluding biliary etiology of AP must be available prior to enrolment as part of the protocol)
- •Treatment with potent CYP3A4-inhibitors (ketoconazol, itraconzol, ritonavir) or P-gp inhibitors (e.g. cyclosporine).
研究组 & 干预措施
Placebo treatment
Film-coated matched placebo-tablets consisting of:
Core:
Mannitol, USP/Ph. Eur./JP Croscarmellose Sodium, NF/Ph. Eur./JP Magnesium Stearate, NF/Ph. Eur./JP
Coating:
Opadry Yellow Purified Water, USP/EP
干预措施: Placebo treatment (Drug)
Naldemedine treatment
Film-coated matched active-tablets consisting of:
Core:
Naldemedine Tosylate (0,2 mg) Mannitol, USP/Ph. Eur./JP Croscarmellose Sodium, NF/Ph. Eur./JP Magnesium Stearate, NF/Ph. Eur./JP
Coating:
Opadry Yellow Purified Water, USP/EP
干预措施: Naldemedine 0.2 MG Oral Tablet (Drug)
结局指标
主要结局
Number of AP attacks verified by the Atlanta Criteria
时间窗: Observation period starts from day of randomization and ends after a minimum of 6 months and a maximum of 12 months
The primary outcome is defined as time to (recurrent) AP attack(s) verified by the Atlanta Criteria between the naldemedine group and the placebo group. The Atlanta Criteria is the current gold standard for the diagnosis of AP attack, and it requires a minimum of two out three of the following features: (i) Abdominal pain typical for acute pancreatitis featuring acute onset of a severe and persistent epigastric pain radiating to the back (ii) Serum amylase levels \> three times greater than the normal upper limit (iii) Findings of pancreatic inflammation in contrast-enhanced computed tomography, magnetic resonance imaging or transabdominal ultrasonography.
次要结局
- Pain intensity(Observation period starts from day of randomization and ends after a minimum of 6 months and a maximum of 12 months)
- Gut function (BSFS)(Day of randomization and at follow up visit after a minimum of 6 months and a maximum of 12 months)
- Gut function (GSRS)(Day of randomization and at follow up visit after a minimum of 6 months and a maximum of 12 months)
- Health resource utilization(Observation period starts from day of randomization and ends after a minimum of 6 months and a maximum of 12 months)
- Pancreatic volume(Day of randomization and at follow up visit after a minimum of 6 months and a maximum of 12 months)
- Endocrine pancreatic function(Day of randomization and at follow up visit after a minimum of 6 months and a maximum of 12 months)
- Impression of change(Day of randomization and at follow up visit after a minimum of 6 months and a maximum of 12 months)
- Exocrine pancreatic function(Day of randomization and at follow up visit after a minimum of 6 months and a maximum of 12 months)
- Quality of life (EORTC QLQ-C30)(Day of randomization and at follow up visit after a minimum of 6 months and a maximum of 12 months)
研究者
Asbjørn Mohr Drewes
Professor, Chief Physician, MD, PhD, DMSc
Aalborg University Hospital