Clinical trial NCT04358133: Low Dose Morphine to Relieve Dyspnea in Acute Respiratory Failure (OPIDYS)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Respiratory Failure
Keywords: Acute respiratory failure
Dyspnea
Opioids
Comfort
Intensive care unit
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2020-04-24
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, double-blind, placebo-controlled, parallel-group,single center, phase 2 pilot study
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Average dyspnea over 24 hours
timeFrame: systematically evaluated every 4 hours over 24 hours and whenever necessary
Secondary outcomes:
measure: Intensity of dyspnea
timeFrame: every 4 hours over 24 hours
measure: Incidence of severe dyspnea (dyspnea ≥40)
timeFrame: within 24 hours
measure: Anxiety
timeFrame: every 4 hours as well as over the first 24 hours
measure: Incidence of moderate to severe anxiety
timeFrame: every 4 hours over 24 hours
measure: Intubation rate
timeFrame: within the first 48 hours
measure: Vigilance level (Glasgow Coma Scale : impaired alertness defined by Glasgow Coma Scale ≤ 12)
timeFrame: every 4 hours as well as the first 48 hours
measure: Incidence of coma
timeFrame: within the first 48 hours
measure: Incidence of delirium
timeFrame: within the first every 4 hours as well as over the first 48 hours
measure: Respiratory rate
timeFrame: every 4 hours as well as over the first 24 hours
measure: Proportion of patients requiring the transition from one oxygenation technique to another
timeFrame: At the end of the study (12 months)
measure: Intensity of pain
timeFrame: every 4 hours
measure: Duration of night sleep the first night
timeFrame: at the end of the first night
measure: Quality of sleep the first night
timeFrame: at the end of the first night
measure: Severity of dry eye
timeFrame: in the first 24 hours
measure: Severity of dry nose
timeFrame: in the first 24 hours
measure: Severity of feeling of gastric distension
timeFrame: in the first 24 hours
measure: Constipation
timeFrame: in the first 48 hours
measure: Nausea
timeFrame: in the first 48 hours
measure: Nurses' adherence to the protocol
timeFrame: in the first 24 hours
measure: Nurses' satisfaction with the protocol
timeFrame: in the first 24 hours
measure: Number of non invasive ventilation sessions
timeFrame: in the first 24 hours
measure: Total duration of non invasive ventilation
timeFrame: in the first 24 hours
measure: Tolerance of non invasive ventilation
timeFrame: in the first 24 hours
measure: Duration of HFNCO (high-flow nasal canula oxygenation)
timeFrame: in the first 24 hours
measure: Tolerance of HFNCO(high-flow nasal canula oxygenation)
timeFrame: in the first 24 hours
measure: Duration of standard oxygen
timeFrame: in the first 24 hours
measure: Tolerance of standard oxygen
timeFrame: in the first 24 hours
measure: Any adverse or serious event occurring
timeFrame: within the first 48 hours
Other outcomes:
Locations:
city: Paris
country: France
facility: Groupe Hospitalier Pitié Salpetriere
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Alexandre DEMOULE, PH
role: STUDY_DIRECTOR
References:
citation: 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.