2025-522546-52-00招募中3 期
Sustained-release oral morphine to alleviate persistent dyspnea in patients with chronic respiratory insufficiency due to amyotrophic lateral sclerosis outside the administration of ventilatory assistance: prospective multicenter randomized, placebo-controlled study, parallel arms. (OPIDYS-ALS).
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 160
- 试验地点
- 6
- 主要终点
- The primary endpoint of the study will be the change in intensity of dyspnea unpleasantness during the worst dyspneic episode experienced in the previous 24 hours, assessed at Day 7 and four weeks after inclusion in the study
研究概览
简要总结
The primary objective is to show that oral sustained-release morphine reduces the unpleasantness of the worst episode of dyspnea experienced during a given day, four weeks after inclusion in the study.
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 否
入选标准
- •age over 18 ;
- •known diagnosis of amyotrophic lateral sclerosis irrespective of the clinical form of the disease, its severity and its progression;
- •chronic respiratory insufficiency with home nocturnal non-invasive mask ventilation established for at least 6 hours per night since 3 months or more (no upper limit);
- •self-report of dyspnea while breathing unassisted during the day (i.e outside nocturnal ventilation), either at rest or for minimal efforts, with a rating of 2 or more on a dyspnea unpleasantness numerical rating scale;
- •affiliation to a social security regime (patients on "aide médicale d'état" will not be included);
- •ability to understand participants' information;
- •prior signing of informed consent .
排除标准
- •Woman of childbearing potential, unless they are using reliable methods of contraception stable for a minimum of 2 months prior to first administration and willing to use it for the entire duration of the study and for one month after the last dosing.
- •Conditions with increased potential for gastrointestinal perforation
- •Clinically important disruptions of the blood-brain barrier
- •permanent dependency on ventilatory assistance (more than 20 hours a day);
- •Myocardial infarction within the past 6 months
- •Patients treated with strong CYP3A4 inducers (e.g. carbamazepine, rifampin, St. John’s Wort)
- •History of opioid abuse
- •presence of a tracheostomy;
- •inability to read and understand the rating scales and questionnaires correctly; the inability to personally fill scoring forms in not a non-inclusion criterion if a caregiver is identified and can provide for this action;
- •known contraindications to the administration of morphine or other opioids (Acute or severe respiratory depression, acute bronchial asthma, paralytic ileus, gastrointestinal obstruction, coma, severe central nervous system depression, known hypersensitivity to morphine or other opioids, acute alcohol intoxication, concomitant use of monoamine oxidase inhibitors or within 14 days of their discontinuation, head injury, raised intracranial pressure, acute abdomen, severe hepatic impairment, severe renal impairment, uncontrolled seizures, delirium tremens, severe hypotension, shock, biliary colic, pancreatitis, pregnancy at or near term, breastfeeding, inability to swallow or risk of aspiration, use in opioid-naïve patients at high doses)
- •another indication for the administration of morphine
- •known severe hepatocellular insufficiency (with encephalopathy)
- •known contraindications to the administration of naloxegol ((Known or suspected gastrointestinal obstruction, risk of recurrent gastrointestinal obstruction, hypersensitivity to naloxegol or excipients, concomitant use of strong CYP3A4 inhibitors (Ketoconazole, itraconazole, posaconazole, voriconazole, clarithromycin, telithromycin, ritonavir, cobicistat, indinavir, nelfinavir, saquinavir, atazanavir, nefazodone, boceprevir, telaprevir, grapefruit juice) severe hepatic impairment (Child–Pugh class C)
- •Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption.
- •known renal insufficiency at inclusion time (confirmed by the last biology by a creatinine clearance < 30 ml/min calculated with the Cockcroft-Gault formula)
- •Women who are pregnant, breastfeeding, or plan to become pregnant while in the trial.
- •known uncontrolled epilepsy
- •swallowing difficulties severe enough to prevent the oral administration of drugs
- •participation in another interventional clinical trial evaluating a health product or any randomized clinical trial
- •under legal protection measure (tutorship or curatorship) and patient deprived of freedom
- •prior diagnosis of concurrent chronic respiratory disease, such as asthma, chronic obstructive pulmonary disease or restrictive lung disease; this criterion will be appreciated by the investigator from the participants medical charts and no further diagnostic procedure will be required;
- •episode of acute respiratory deterioration resolved less than 3 weeks before inclusion;
- •Hypercapnia associated with an arterial blood pH below 7.38
结局指标
主要结局
The primary endpoint of the study will be the change in intensity of dyspnea unpleasantness during the worst dyspneic episode experienced in the previous 24 hours, assessed at Day 7 and four weeks after inclusion in the study
The primary endpoint of the study will be the change in intensity of dyspnea unpleasantness during the worst dyspneic episode experienced in the previous 24 hours, assessed at Day 7 and four weeks after inclusion in the study
次要结局
- Endpoints evaluating the efficacy of the treatment on dyspnea: The change in the intensity of dyspnea unpleasantness NRS evaluation, The evolution of dyspnea unpleasantness, The description of dyspnea according to the "Dyspnea ALS-15, The multidimensional description of dyspnea according to the Multidimensional Dyspnea Profile (MDP), The intensity of dyspnea-related anxiety evaluated on a 0-10 NRS, The time spent daily under mechanical ventilation (mechanical ventilator recordings),
- Endpoints evaluating the efficacy of the treatment on outcomes other than dyspnea and on quality of life, The intensity of pain evaluated on a 0-10 NRS, Health-related quality of life (HRQoL), evaluated,in a general manner, using the 12-Item Short-Form Health Survey (SF12) , Sleep quality evaluated using the Pittsburgh Sleep Quality Index (PSQI)
- Endpoints evaluating the impact of the treatment on the patients' closest informal caregiver: The intensity of general anxiety evaluated on a 0-10 NRS, The intensity of dyspnea-related anxiety evaluated on a 0-10 NRS, The intensity of the burden of care weighing on the patients' designated closest relatives, if any, using the revised 22-item Zarit Burden Interview (ZBI), The quality of life of the patients' designated closest relatives, if any, using the questionnaire (WHOQOL-BREF).
- Endpoints evaluating the tolerance of the treatment : The incidence of adverse events will be evaluated during each interaction with the graded according to CTCAE, . respiratory frequency during unassisted breathing, transcutaneous pulsed oxygen saturation during unassisted breathing, and arterial blood gases during unassisted breathing, Opioid-induced constipation. Opioid-induced constipation will be assessed as a predefined secondary endpoint related to treatment tolerance
研究者
thomas SIMILOWSKI
Scientific
Assistance Publique Hopitaux De Paris
研究点 (6)
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