Clinical Research Directory

Browse clinical research sites, groups, and studies.

Sites Groups Studies

Back to Studies

RECRUITING

NCT04427826

PHASE1/PHASE2

Efficacy of Morphine in Reducing the Rate of Early Non-Invasive Ventilation Failure in Acute Exacerbation of Chronic Obstructive Pulmonary Disease, Phase I/IIa

Sponsor: University Hospital, Grenoble

View on ClinicalTrials.gov

Summary

Acute exacerbations of Chronic Obstructive Pulmonary Disease (COPD) are a major source of morbidity and mortality for patients and cost to the society. In case of acute respiratory failure with hypercapnia and acidosis, Non Invasive Ventilation (NIV) is preferred as a first line treatment. NIV failures are not uncommon, from 15% in intensive care to 25 - 30% in emergency departments. They most often occur at the start of the NIV or in the hours that follow. There are many reasons for these failure. Among these are; dyspnea, discomfort, the pain related to the exacerbation and also to the NIV are frequently noted. The use of certain drugs with anxiolytic, hypnotic and/or analgesic properties could also be useful. Some sedatives and opioids have already been studied in this indication but without a therapeutic trial and satisfactory methodology. Among the molecules of interest, Morphine seems interesting . It's administration could reduce the ventilatory rate, intensity of dyspnea, pain and anxiety as well as dynamic hyperinflation. The investigators believe that morphine administration will decrease the rate of early NIV failure by improving comfort (decreased dyspnea and pain) and ventilation (decreased respiratory rate and increase in tidal volume) in patients with exacerbations of COPD. However, before considering a randomized phase III efficacy study, it is necessary to determine the optimal dose of morphine in this indication, through a phase I/II dose-finding study taking into accounts both the efficacy and toxicity of morphine. The main objective of this study, is to determine the optimal dose of morphine administered at the initiation of NIV in patient with acute Exacerbation of Chronic Obstructive Pulmonary Disease (COPD), which is defined as the maximum gain function combining the probability of dose-limiting toxicity with PaCO2.Therefore, the impact of morphine administration on the physiological parameters of NIV- COPD exacerbation patients will be assessed.

Official title: Efficacy of Morphine in Reducing the Rate of Early Non-Invasive Ventilation (NIV) Failure in Acute Exacerbation of Chronic Obstructive Pulmonary Disease (COPD), Phase I/IIa

Key Details

Gender

All

Age Range

18 Years - Any

Study Type

INTERVENTIONAL

Enrollment

Start Date

2020-12-08

Completion Date

2027-01

Last Updated

2023-11-29

Healthy Volunteers

Conditions

Chronic Obstructive Pulmonary Disease

Interventions

DRUG

Morphine hydrochloride

A single open-label injection of morphine (T0) at the dose closest to that defined by the model (estimation by Bayesian method) from among the following 4 doses: 0.02; 0.04; 0.07 and 0.1mg/kg will be adminestred to the patients.

Inclusion Criteria: * Patients Aged ≥ 18 years * Current or former smoker at least 10 packs-years * Patient with a history of COPD according to the Gold guidelines , after review of the medical record by the physician in charge * Acute exacerbation of COPD (greater degradation of respiratory symptoms than the usual daily variations and requiring a modification of therapeutic management) * Need to implement NIV treatment (respiratory acidosis with pH\<7.35) * Ventilation frequency \> 20min * Affiliation to the French security system (or equivalent) * Written informed consent from the patient or his surrogates. In patients who are not able to consent on admission an emergency inclusion procedure will be allowed, with a mandatory delayed consent. Exclusion Criteria: * Patient already treated by NIV during admission (e. g. introduction in pre-hospital by SMUR) or started more than one hour ago in the department. * Sedative (barbiturates, benzodiazepines and related substances and other sedatives) or morphine treatment within 24 hours before inclusion * Chronic alcoholism * Contra-indication to NIV: disturbances of consciousness (Glasgow \< 11) except moderate hypercapnic encephalopathy; indication of immediate intubation; risk of inhalation; sputum impossible; hemodynamic instability; inability to remove the mask; trauma, surgery or facial malformation; patients with pH \< 7.25 can only be included in intensive care unit or in the vital emergency room of the emergency department, under continuous monitoring * NIV with palliative purpose from the outset with death expected within 24 hours of inclusion * Non-communicative patient or significant dementia making them unable to participate in the study * Contra-indication to morphine without acute respiratory distress * Pregnant or breastfeeding women * Major mentioned in Articles L1121-6 and 1121-8 of French public health cod * Patients in a period of exclusion from other research involving the human person type 1 or 2 * Subject cannot be contacted in case of emergency

Locations (1)

Emergency Department of Grenoble Alpes University Hospital

Grenoble, Isère, Auvergne-Rhône-Alpes, France