Low Dose Morphine to Relieve Dyspnea in Acute Respiratory Failure (OPIDYS) (OPIDYS)
Primary Purpose
Acute Respiratory Failure
Status
Completed
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Chlorhydrate de morphine
NaCl 0,9%,
Sponsored by
About this trial
This is an interventional treatment trial for Acute Respiratory Failure focused on measuring Acute respiratory failure, Dyspnea, Opioids, Comfort, Intensive care unit
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
Sites / Locations
- Groupe Hospitalier Pitié Salpetriere
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Chlorhydrate de morphine
NaCl 0,9%
Arm Description
initial dose of 2 mg, followed by 1 mg every 3 minutes until a VAS-dyspnea <40 then relay subcut
initial dose of 2 mg, followed by 1 mg every 3 minutes until a VAS-dyspnea <40 then relay subcut
Outcomes
Primary Outcome Measures
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).
Secondary Outcome Measures
Intensity of dyspnea
patient reported outcome measure (PRO) ; min=0;max=100(worse)
Incidence of severe dyspnea (dyspnea ≥40)
patient reported outcome measure (PRO) ; min=0;max=100(worse)
Anxiety
Patient reported outcome measure (PRO) ; min=0;max=100(worse)
Incidence of moderate to severe anxiety
Incidence of moderate to severe anxiety (PRO) ; min=0;max=100(worse)
Intubation rate
Intubation rate
Vigilance level (Glasgow Coma Scale : impaired alertness defined by Glasgow Coma Scale ≤ 12)
Vigilance level ; GCS : min=3(worse) ;max=15
Incidence of coma
Incidence of coma
Incidence of delirium
Incidence of delirium
Respiratory rate
Respiratory rate
Proportion of patients requiring the transition from one oxygenation technique to another
Proportion of patients requiring the transition from one oxygenation technique to another
Intensity of pain
Patient reported outcome measure (PRO) ; min=0;max=100(worse)
Duration of night sleep the first night
Duration of night sleep the first night (number of hours)
Quality of sleep the first night
Patient reported outcome measure (PRO); min=0;max=100(worse)
Severity of dry eye
Patient reported outcome criteria (PRO); min=0;max=100(worse)
Severity of dry nose
Patient reported outcome criteria (PRO); min=0;max=100(worse)
Severity of feeling of gastric distension
Patient reported outcome criteria (PRO); min=0;max=100(worse)
Constipation
Constipation (PRO); min=0;max=100(worse)
Nausea
Patient reported outcome criteria (PRO) ;min=0;max=100(worse)
Nurses' adherence to the protocol
Nurses' adherence to the protocol (questionnaire)
Nurses' satisfaction with the protocol
Nurses' satisfaction with the protocol (questionnaire)
Number of non invasive ventilation sessions
Number of non invasive ventilation sessions
Total duration of non invasive ventilation
Total duration of non invasive ventilation (number of hours)
Tolerance of non invasive ventilation
Tolerance of non invasive ventilation (PRO) ;min=0;max=100(worse)
Duration of HFNCO (high-flow nasal canula oxygenation)
Duration of HFNCO (number of hours)
Tolerance of HFNCO(high-flow nasal canula oxygenation)
Tolerance of HFNCO : number of adverses events
Duration of standard oxygen
Duration of standard oxygen (number of hours)
Tolerance of standard oxygen
Tolerance of standard oxygen : number of adverses events
Any adverse or serious event occurring
Any adverse or serious event occurring
Full Information
NCT ID
NCT04358133
First Posted
March 31, 2020
Last Updated
October 24, 2022
Sponsor
Assistance Publique - Hôpitaux de Paris
1. Study Identification
Unique Protocol Identification Number
NCT04358133
Brief Title
Low Dose Morphine to Relieve Dyspnea in Acute Respiratory Failure (OPIDYS)
Acronym
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
2. Study Status
Record Verification Date
October 2022
Overall Recruitment Status
Completed
Study Start Date
December 16, 2020 (Actual)
Primary Completion Date
October 7, 2022 (Actual)
Study Completion Date
October 7, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Respiratory Failure
Keywords
Acute respiratory failure, Dyspnea, Opioids, Comfort, Intensive care unit
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Randomized, double-blind, placebo-controlled, parallel-group,single center, phase 2 pilot study
Masking
ParticipantCare ProviderInvestigator
Masking Description
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
Allocation
Randomized
Enrollment
23 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Chlorhydrate de morphine
Arm Type
Experimental
Arm Description
initial dose of 2 mg, followed by 1 mg every 3 minutes until a VAS-dyspnea <40 then relay subcut
Arm Title
NaCl 0,9%
Arm Type
Placebo Comparator
Arm Description
initial dose of 2 mg, followed by 1 mg every 3 minutes until a VAS-dyspnea <40 then relay subcut
Intervention Type
Drug
Intervention Name(s)
Chlorhydrate de morphine
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
NaCl 0,9%,
Intervention Description
The control group will receive placebo NaCl 0.9% administered according to the same protocol as the experimental arm
Primary Outcome Measure Information:
Title
Average dyspnea over 24 hours
Description
Dyspnea will be assessed by VAS-dyspnea (ranging from zero, no dyspnea to 100, worst possible dyspnea) patient reported outcome criteria (PRO).
Time Frame
systematically evaluated every 4 hours over 24 hours and whenever necessary
Secondary Outcome Measure Information:
Title
Intensity of dyspnea
Description
patient reported outcome measure (PRO) ; min=0;max=100(worse)
Time Frame
every 4 hours over 24 hours
Title
Incidence of severe dyspnea (dyspnea ≥40)
Description
patient reported outcome measure (PRO) ; min=0;max=100(worse)
Time Frame
within 24 hours
Title
Anxiety
Description
Patient reported outcome measure (PRO) ; min=0;max=100(worse)
Time Frame
every 4 hours as well as over the first 24 hours
Title
Incidence of moderate to severe anxiety
Description
Incidence of moderate to severe anxiety (PRO) ; min=0;max=100(worse)
Time Frame
every 4 hours over 24 hours
Title
Intubation rate
Description
Intubation rate
Time Frame
within the first 48 hours
Title
Vigilance level (Glasgow Coma Scale : impaired alertness defined by Glasgow Coma Scale ≤ 12)
Description
Vigilance level ; GCS : min=3(worse) ;max=15
Time Frame
every 4 hours as well as the first 48 hours
Title
Incidence of coma
Description
Incidence of coma
Time Frame
within the first 48 hours
Title
Incidence of delirium
Description
Incidence of delirium
Time Frame
within the first every 4 hours as well as over the first 48 hours
Title
Respiratory rate
Description
Respiratory rate
Time Frame
every 4 hours as well as over the first 24 hours
Title
Proportion of patients requiring the transition from one oxygenation technique to another
Description
Proportion of patients requiring the transition from one oxygenation technique to another
Time Frame
At the end of the study (12 months)
Title
Intensity of pain
Description
Patient reported outcome measure (PRO) ; min=0;max=100(worse)
Time Frame
every 4 hours
Title
Duration of night sleep the first night
Description
Duration of night sleep the first night (number of hours)
Time Frame
at the end of the first night
Title
Quality of sleep the first night
Description
Patient reported outcome measure (PRO); min=0;max=100(worse)
Time Frame
at the end of the first night
Title
Severity of dry eye
Description
Patient reported outcome criteria (PRO); min=0;max=100(worse)
Time Frame
in the first 24 hours
Title
Severity of dry nose
Description
Patient reported outcome criteria (PRO); min=0;max=100(worse)
Time Frame
in the first 24 hours
Title
Severity of feeling of gastric distension
Description
Patient reported outcome criteria (PRO); min=0;max=100(worse)
Time Frame
in the first 24 hours
Title
Constipation
Description
Constipation (PRO); min=0;max=100(worse)
Time Frame
in the first 48 hours
Title
Nausea
Description
Patient reported outcome criteria (PRO) ;min=0;max=100(worse)
Time Frame
in the first 48 hours
Title
Nurses' adherence to the protocol
Description
Nurses' adherence to the protocol (questionnaire)
Time Frame
in the first 24 hours
Title
Nurses' satisfaction with the protocol
Description
Nurses' satisfaction with the protocol (questionnaire)
Time Frame
in the first 24 hours
Title
Number of non invasive ventilation sessions
Description
Number of non invasive ventilation sessions
Time Frame
in the first 24 hours
Title
Total duration of non invasive ventilation
Description
Total duration of non invasive ventilation (number of hours)
Time Frame
in the first 24 hours
Title
Tolerance of non invasive ventilation
Description
Tolerance of non invasive ventilation (PRO) ;min=0;max=100(worse)
Time Frame
in the first 24 hours
Title
Duration of HFNCO (high-flow nasal canula oxygenation)
Description
Duration of HFNCO (number of hours)
Time Frame
in the first 24 hours
Title
Tolerance of HFNCO(high-flow nasal canula oxygenation)
Description
Tolerance of HFNCO : number of adverses events
Time Frame
in the first 24 hours
Title
Duration of standard oxygen
Description
Duration of standard oxygen (number of hours)
Time Frame
in the first 24 hours
Title
Tolerance of standard oxygen
Description
Tolerance of standard oxygen : number of adverses events
Time Frame
in the first 24 hours
Title
Any adverse or serious event occurring
Description
Any adverse or serious event occurring
Time Frame
within the first 48 hours
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alexandre DEMOULE, PH
Organizational Affiliation
Assistance Publique - Hôpitaux de Paris
Official's Role
Study Director
Facility Information:
Facility Name
Groupe Hospitalier Pitié Salpetriere
City
Paris
ZIP/Postal Code
75013
Country
France
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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.
Citations:
PubMed Identifier
36175968
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.
Results Reference
derived
Learn more about this trial
Low Dose Morphine to Relieve Dyspnea in Acute Respiratory Failure (OPIDYS)
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