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

NCT ID: NCT04358133

Last Updated: 2022-10-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-12-16
• Study Completion Date: 2022-10-07

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.

Conditions

Acute Respiratory Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Chlorhydrate de morphine

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

Group Type: EXPERIMENTAL

Chlorhydrate de morphine

Intervention Type: DRUG

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%

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

Group Type: PLACEBO_COMPARATOR

NaCl 0,9%,

Intervention Type: DRUG

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

Interventions

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

Intervention Type: DRUG

NaCl 0,9%,

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

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Alexandre DEMOULE, PH

Role: STUDY_DIRECTOR

Assistance Publique - Hôpitaux de Paris

Locations

Groupe Hospitalier Pitié Salpetriere

Paris, , France

Countries

France

References

Deleris R, Bureau C, Lebbah S, Decavele M, Dres M, Mayaux J, Similowski T, Dechartres A, Demoule A. Low dose of morphine to relieve dyspnea in acute respiratory failure: the OpiDys double-blind randomized controlled trial. Respir Res. 2024 Jul 16;25(1):280. doi: 10.1186/s12931-024-02867-2.

Reference Type: DERIVED

PMID: 39014448 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 36175968 (View on PubMed)

Other Identifiers

2019-003091-39

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CRC18023

Identifier Type: -

Identifier Source: org_study_id