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

Acute Respiratory Failure Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04358133
• Other study ID #: CRC18023
• Secondary ID: 2019-003091-39
• Status: Completed
• Phase: Phase 2
• Start date: December 16, 2020
• Est. completion date: October 7, 2022

Study information

• Verified date: October 2022
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 23
• Est. completion date: October 7, 2022
• Est. primary completion date: October 7, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Respiratory Failure
• Dyspnea
• Respiratory Distress Syndrome
• Respiratory Insufficiency

Intervention

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
• NaCl 0,9%,
The control group will receive placebo NaCl 0.9% administered according to the same protocol as the experimental arm

Locations

Country	Name	City	State
France	Groupe Hospitalier Pitié Salpetriere	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Intensity of dyspnea	patient reported outcome measure (PRO) ; min=0;max=100(worse)	every 4 hours over 24 hours
Secondary	Incidence of severe dyspnea (dyspnea =40)	patient reported outcome measure (PRO) ; min=0;max=100(worse)	within 24 hours
Secondary	Anxiety	Patient reported outcome measure (PRO) ; min=0;max=100(worse)	every 4 hours as well as over the first 24 hours
Secondary	Incidence of moderate to severe anxiety	Incidence of moderate to severe anxiety (PRO) ; min=0;max=100(worse)	every 4 hours over 24 hours
Secondary	Intubation rate	Intubation rate	within the first 48 hours
Secondary	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
Secondary	Incidence of coma	Incidence of coma	within the first 48 hours
Secondary	Incidence of delirium	Incidence of delirium	within the first every 4 hours as well as over the first 48 hours
Secondary	Respiratory rate	Respiratory rate	every 4 hours as well as over the first 24 hours
Secondary	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)
Secondary	Intensity of pain	Patient reported outcome measure (PRO) ; min=0;max=100(worse)	every 4 hours
Secondary	Duration of night sleep the first night	Duration of night sleep the first night (number of hours)	at the end of the first night
Secondary	Quality of sleep the first night	Patient reported outcome measure (PRO); min=0;max=100(worse)	at the end of the first night
Secondary	Severity of dry eye	Patient reported outcome criteria (PRO); min=0;max=100(worse)	in the first 24 hours
Secondary	Severity of dry nose	Patient reported outcome criteria (PRO); min=0;max=100(worse)	in the first 24 hours
Secondary	Severity of feeling of gastric distension	Patient reported outcome criteria (PRO); min=0;max=100(worse)	in the first 24 hours
Secondary	Constipation	Constipation (PRO); min=0;max=100(worse)	in the first 48 hours
Secondary	Nausea	Patient reported outcome criteria (PRO) ;min=0;max=100(worse)	in the first 48 hours
Secondary	Nurses' adherence to the protocol	Nurses' adherence to the protocol (questionnaire)	in the first 24 hours
Secondary	Nurses' satisfaction with the protocol	Nurses' satisfaction with the protocol (questionnaire)	in the first 24 hours
Secondary	Number of non invasive ventilation sessions	Number of non invasive ventilation sessions	in the first 24 hours
Secondary	Total duration of non invasive ventilation	Total duration of non invasive ventilation (number of hours)	in the first 24 hours
Secondary	Tolerance of non invasive ventilation	Tolerance of non invasive ventilation (PRO) ;min=0;max=100(worse)	in the first 24 hours
Secondary	Duration of HFNCO (high-flow nasal canula oxygenation)	Duration of HFNCO (number of hours)	in the first 24 hours
Secondary	Tolerance of HFNCO(high-flow nasal canula oxygenation)	Tolerance of HFNCO : number of adverses events	in the first 24 hours
Secondary	Duration of standard oxygen	Duration of standard oxygen (number of hours)	in the first 24 hours
Secondary	Tolerance of standard oxygen	Tolerance of standard oxygen : number of adverses events	in the first 24 hours
Secondary	Any adverse or serious event occurring	Any adverse or serious event occurring	within the first 48 hours