Low Dose Morphine to Relieve Dyspnea in Acute Respiratory Failure (OPIDYS) (OPIDYS)

Relieving Dyspnea With Low Dose of Morphine in Patients Admitted to the Intensive Care Unit for an Acute Respiratory Failure: a Double-blind Randomized Controlled Pilot Study

This study evaluates a pharmacological intervention to relieve dyspnea in intensive care unit patients. Indeed, opioids can be particularly beneficial since 1) dyspnea and pain share many similarities, 2) the benefit of opioids on dyspnea has been clearly demonstrated in other populations. However, to date, data regarding the impact of morphine on dyspnea in intensive care unit patients admitted for acute respiratory failure are scarce. There may be a reluctance of physicians to prescribe opioids that is not scientifically justified.

The study will focus on patient reported outcome (PRO) criteria. The ultimate goal of this pilot study is to design the protocol of a future pragmatic trial.

Study Overview

• Status: Completed
• Conditions: Acute Respiratory Failure
• Intervention / Treatment: Drug: Chlorhydrate de morphine; Drug: NaCl 0,9%,

Detailed Description

Randomized, double-blind, placebo-controlled, parallel-group, single-center phase 2 pilot study.The experimental group will receive an intravenous titration of morphine followed by a subcutaneous administration of morphine hydrochloride for 24 hours according to a predefined protocol. The control group will receive placebo NaCl 0.9% administered according to the same protocol as the experimental arm Patients will be randomized 1:1 between low-dose titrated morphine (experimental group) and placebo (control group). The other treatments will be similar in both groups, according to the protocol and the recommendations.

Severe dyspnea will be assessed for regularly Patients will be followed for 48 hours: 24-hour treatment duration, evaluation of primary endpoint for first 24 hours, collection of adverse events for 48 hours.

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Paris, France, 75013
    • Groupe Hospitalier Pitié Salpêtrière

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult patients ≤ 75 years
• Admitted in intensive care for an acute respiratory failure defined as a respiratory rate> 24 / min or signs of respiratory distress such as labored breathing or paradoxical inspiration, or SpO2 <90% in ambient air
• Spontaneous ventilation, either under standard oxygen, high flow oxygen or non invasive ventilation
• Dyspnea ≥ 40 on an dyspnea-VAS from zero (no dyspnea) to 100 (worst possible dyspnea)
• Richmond agitation and sedation scale (RASS) between 0 and 2.
• No confusion, as defined by the CAM-ICU
• Signed informed consent

Exclusion Criteria:

• Intubated patient
• Intubation planned upon admission
• Hearing or visual impairment
• Insufficient command of French
• Previous psychiatric or cognitive disorders known
• Moribund patient
• Known hypersensitivity to opioids
• Severe renal insufficiency (creatinine clearance <30 ml / min)
• Severe hepatocellular insufficiency (factor V <50%)
• Any formal contra-indication of opiates
• Opioid use within the 24 hours before inclusion
• Pregnancy or breastfeeding
• Minor and protected adult
• Exclusion period due to inclusion in another clinical trial
• Previous inclusion in this study
• No affiliation to social security

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Chlorhydrate de morphine; initial dose of 2 mg, followed by 1 mg every 3 minutes until a VAS-dyspnea <40 then relay subcut	Drug: Chlorhydrate de morphine; The experimental group will receive an intravenous titration of morphine followed by a subcutaneous administration of morphine hydrochloride for 24 hours according to a predefined protocol
Placebo Comparator: NaCl 0,9%; initial dose of 2 mg, followed by 1 mg every 3 minutes until a VAS-dyspnea <40 then relay subcut	Drug: NaCl 0,9%,; The control group will receive placebo NaCl 0.9% administered according to the same protocol as the experimental arm

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average dyspnea over 24 hours	Dyspnea will be assessed by VAS-dyspnea (ranging from zero, no dyspnea to 100, worst possible dyspnea) patient reported outcome criteria (PRO).	systematically evaluated every 4 hours over 24 hours and whenever necessary

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intensity of dyspnea	patient reported outcome measure (PRO) ; min=0;max=100(worse)	every 4 hours over 24 hours
Incidence of severe dyspnea (dyspnea ≥40)	patient reported outcome measure (PRO) ; min=0;max=100(worse)	within 24 hours
Anxiety	Patient reported outcome measure (PRO) ; min=0;max=100(worse)	every 4 hours as well as over the first 24 hours
Incidence of moderate to severe anxiety	Incidence of moderate to severe anxiety (PRO) ; min=0;max=100(worse)	every 4 hours over 24 hours
Intubation rate	Intubation rate	within the first 48 hours
Vigilance level (Glasgow Coma Scale : impaired alertness defined by Glasgow Coma Scale ≤ 12)	Vigilance level ; GCS : min=3(worse) ;max=15	every 4 hours as well as the first 48 hours
Incidence of coma	Incidence of coma	within the first 48 hours
Incidence of delirium	Incidence of delirium	within the first every 4 hours as well as over the first 48 hours
Respiratory rate	Respiratory rate	every 4 hours as well as over the first 24 hours
Proportion of patients requiring the transition from one oxygenation technique to another	Proportion of patients requiring the transition from one oxygenation technique to another	At the end of the study (12 months)
Intensity of pain	Patient reported outcome measure (PRO) ; min=0;max=100(worse)	every 4 hours
Duration of night sleep the first night	Duration of night sleep the first night (number of hours)	at the end of the first night
Quality of sleep the first night	Patient reported outcome measure (PRO); min=0;max=100(worse)	at the end of the first night
Severity of dry eye	Patient reported outcome criteria (PRO); min=0;max=100(worse)	in the first 24 hours
Severity of dry nose	Patient reported outcome criteria (PRO); min=0;max=100(worse)	in the first 24 hours
Severity of feeling of gastric distension	Patient reported outcome criteria (PRO); min=0;max=100(worse)	in the first 24 hours
Constipation	Constipation (PRO); min=0;max=100(worse)	in the first 48 hours
Nausea	Patient reported outcome criteria (PRO) ;min=0;max=100(worse)	in the first 48 hours
Nurses' adherence to the protocol	Nurses' adherence to the protocol (questionnaire)	in the first 24 hours
Nurses' satisfaction with the protocol	Nurses' satisfaction with the protocol (questionnaire)	in the first 24 hours
Number of non invasive ventilation sessions	Number of non invasive ventilation sessions	in the first 24 hours
Total duration of non invasive ventilation	Total duration of non invasive ventilation (number of hours)	in the first 24 hours
Tolerance of non invasive ventilation	Tolerance of non invasive ventilation (PRO) ;min=0;max=100(worse)	in the first 24 hours
Duration of HFNCO (high-flow nasal canula oxygenation)	Duration of HFNCO (number of hours)	in the first 24 hours
Tolerance of HFNCO(high-flow nasal canula oxygenation)	Tolerance of HFNCO : number of adverses events	in the first 24 hours
Duration of standard oxygen	Duration of standard oxygen (number of hours)	in the first 24 hours
Tolerance of standard oxygen	Tolerance of standard oxygen : number of adverses events	in the first 24 hours
Any adverse or serious event occurring	Any adverse or serious event occurring	within the first 48 hours

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Study Director: Alexandre DEMOULE, PH, Assistance Publique - Hôpitaux de Paris

Publications and helpful links

General Publications

• Demoule A, Deleris R, Bureau C, Lebbah S, Decavele M, Dres M, Similowski T, Dechartres A. Low dose of morphine to relieve dyspnea in acute respiratory failure (OpiDys): protocol for a double-blind randomized controlled study. Trials. 2022 Sep 30;23(1):828. doi: 10.1186/s13063-022-06754-3.

Study record dates

Study Major Dates

• Study Start (Actual): December 16, 2020
• Primary Completion (Actual): October 7, 2022
• Study Completion (Actual): October 7, 2022

Study Registration Dates

• First Submitted: March 31, 2020
• First Submitted That Met QC Criteria: April 21, 2020
• First Posted (Actual): April 24, 2020

Study Record Updates

• Last Update Posted (Actual): October 25, 2022
• Last Update Submitted That Met QC Criteria: October 24, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Intensive care unit; Dyspnea; Opioids; Comfort; Acute respiratory failure
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Signs and Symptoms, Respiratory; Respiratory Insufficiency; Respiratory Distress Syndrome; Dyspnea; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Morphine
• Other Study ID Numbers: CRC18023; 2019-003091-39 (EudraCT Number)

Plan for Individual participant data (IPD)

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

IPD Plan Description

Data are available upon reasonable request The procedures carried out with the French data privacy authority (CNIL, Commission nationale de l'informatique et des libertés) do not provide for the transmission of the database, nor do the information and consent documents signed by the patients.

Consultation by the editorial board or interested researchers of individual participant data that underlie the results reported in the article after deidentification may nevertheless be considered, subject to prior determination of the terms and conditions of such consultation and in respect for compliance with the applicable regulations.

• IPD Sharing Time Frame: Beginning 3 months and ending 3 years following article publication. Requests out of these time frame can also be submitted to the sponsor
• IPD Sharing Access Criteria: Researchers who provide a methodologically sound proposal.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF)

Drug and device information, study documents

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