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

Phase 2
Completed
Conditions
Acute Respiratory Failure
Interventions
Registration Number
NCT04358133
Lead Sponsor
Assistance Publique - Hôpitaux de Paris
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
23
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Chlorhydrate de morphineChlorhydrate de morphineinitial dose of 2 mg, followed by 1 mg every 3 minutes until a VAS-dyspnea \<40 then relay subcut
NaCl 0,9%NaCl 0,9%,initial dose of 2 mg, followed by 1 mg every 3 minutes until a VAS-dyspnea \<40 then relay subcut
Primary Outcome Measures
NameTimeMethod
Average dyspnea over 24 hourssystematically evaluated every 4 hours over 24 hours and whenever necessary

Dyspnea will be assessed by VAS-dyspnea (ranging from zero, no dyspnea to 100, worst possible dyspnea) patient reported outcome criteria (PRO).

Secondary Outcome Measures
NameTimeMethod
Intubation ratewithin the first 48 hours

Intubation rate

Nauseain the first 48 hours

Patient reported outcome criteria (PRO) ;min=0;max=100(worse)

Total duration of non invasive ventilationin the first 24 hours

Total duration of non invasive ventilation (number of hours)

Tolerance of standard oxygenin the first 24 hours

Tolerance of standard oxygen : number of adverses events

Duration of HFNCO (high-flow nasal canula oxygenation)in the first 24 hours

Duration of HFNCO (number of hours)

Intensity of dyspneaevery 4 hours over 24 hours

patient reported outcome measure (PRO) ; min=0;max=100(worse)

Anxietyevery 4 hours as well as over the first 24 hours

Patient reported outcome measure (PRO) ; min=0;max=100(worse)

Duration of night sleep the first nightat the end of the first night

Duration of night sleep the first night (number of hours)

Severity of dry eyein the first 24 hours

Patient reported outcome criteria (PRO); min=0;max=100(worse)

Incidence of severe dyspnea (dyspnea ≥40)within 24 hours

patient reported outcome measure (PRO) ; min=0;max=100(worse)

Proportion of patients requiring the transition from one oxygenation technique to anotherAt the end of the study (12 months)

Proportion of patients requiring the transition from one oxygenation technique to another

Tolerance of HFNCO(high-flow nasal canula oxygenation)in the first 24 hours

Tolerance of HFNCO : number of adverses events

Incidence of comawithin the first 48 hours

Incidence of coma

Respiratory rateevery 4 hours as well as over the first 24 hours

Respiratory rate

Severity of feeling of gastric distensionin the first 24 hours

Patient reported outcome criteria (PRO); min=0;max=100(worse)

Constipationin the first 48 hours

Constipation (PRO); min=0;max=100(worse)

Number of non invasive ventilation sessionsin the first 24 hours

Number of non invasive ventilation sessions

Incidence of moderate to severe anxietyevery 4 hours over 24 hours

Incidence of moderate to severe anxiety (PRO) ; min=0;max=100(worse)

Intensity of painevery 4 hours

Patient reported outcome measure (PRO) ; min=0;max=100(worse)

Quality of sleep the first nightat the end of the first night

Patient reported outcome measure (PRO); min=0;max=100(worse)

Nurses' adherence to the protocolin the first 24 hours

Nurses' adherence to the protocol (questionnaire)

Nurses' satisfaction with the protocolin the first 24 hours

Nurses' satisfaction with the protocol (questionnaire)

Tolerance of non invasive ventilationin the first 24 hours

Tolerance of non invasive ventilation (PRO) ;min=0;max=100(worse)

Duration of standard oxygenin the first 24 hours

Duration of standard oxygen (number of hours)

Vigilance level (Glasgow Coma Scale : impaired alertness defined by Glasgow Coma Scale ≤ 12)every 4 hours as well as the first 48 hours

Vigilance level ; GCS : min=3(worse) ;max=15

Incidence of deliriumwithin the first every 4 hours as well as over the first 48 hours

Incidence of delirium

Severity of dry nosein the first 24 hours

Patient reported outcome criteria (PRO); min=0;max=100(worse)

Any adverse or serious event occurringwithin the first 48 hours

Any adverse or serious event occurring

Trial Locations

Locations (1)

Groupe Hospitalier Pitié Salpetriere

🇫🇷

Paris, France

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