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Clinical Trials/NCT04358133
NCT04358133
Completed
Phase 2

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

Assistance Publique - Hôpitaux de Paris1 site in 1 country23 target enrollmentDecember 16, 2020

Overview

Phase
Phase 2
Intervention
Chlorhydrate de morphine
Conditions
Acute Respiratory Failure
Sponsor
Assistance Publique - Hôpitaux de Paris
Enrollment
23
Locations
1
Primary Endpoint
Average dyspnea over 24 hours
Status
Completed
Last Updated
3 years ago

Overview

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.

Registry
clinicaltrials.gov
Start Date
December 16, 2020
End Date
October 7, 2022
Last Updated
3 years ago
Study Type
Interventional
Study Design
Parallel
Sex
All

Investigators

Responsible Party
Sponsor

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
  • 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

Arms & Interventions

Chlorhydrate de morphine

initial dose of 2 mg, followed by 1 mg every 3 minutes until a VAS-dyspnea \<40 then relay subcut

Intervention: Chlorhydrate de morphine

NaCl 0,9%

initial dose of 2 mg, followed by 1 mg every 3 minutes until a VAS-dyspnea \<40 then relay subcut

Intervention: NaCl 0,9%,

Outcomes

Primary Outcomes

Average dyspnea over 24 hours

Time Frame: systematically 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 Outcomes

  • Duration of HFNCO (high-flow nasal canula oxygenation)(in the first 24 hours)
  • Tolerance of standard oxygen(in the first 24 hours)
  • Intensity of dyspnea(every 4 hours over 24 hours)
  • Anxiety(every 4 hours as well as over the first 24 hours)
  • Duration of night sleep the first night(at the end of the first night)
  • Severity of dry eye(in the first 24 hours)
  • Nausea(in the first 48 hours)
  • Total duration of non invasive ventilation(in the first 24 hours)
  • Incidence of severe dyspnea (dyspnea ≥40)(within 24 hours)
  • Proportion of patients requiring the transition from one oxygenation technique to another(At the end of the study (12 months))
  • Tolerance of HFNCO(high-flow nasal canula oxygenation)(in the first 24 hours)
  • Intubation rate(within the first 48 hours)
  • Incidence of coma(within the first 48 hours)
  • Respiratory rate(every 4 hours as well as over the first 24 hours)
  • Severity of feeling of gastric distension(in the first 24 hours)
  • Constipation(in the first 48 hours)
  • Number of non invasive ventilation sessions(in the first 24 hours)
  • Intensity of pain(every 4 hours)
  • Quality of sleep the first night(at the end of the first night)
  • Incidence of moderate to severe anxiety(every 4 hours over 24 hours)
  • Nurses' adherence to the protocol(in the first 24 hours)
  • Nurses' satisfaction with the protocol(in the first 24 hours)
  • Tolerance of non invasive ventilation(in the first 24 hours)
  • Duration of standard oxygen(in the first 24 hours)
  • Vigilance level (Glasgow Coma Scale : impaired alertness defined by Glasgow Coma Scale ≤ 12)(every 4 hours as well as the first 48 hours)
  • Incidence of delirium(within the first every 4 hours as well as over the first 48 hours)
  • Severity of dry nose(in the first 24 hours)
  • Any adverse or serious event occurring(within the first 48 hours)

Study Sites (1)

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