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

Assistance Publique - Hôpitaux de Paris

Status and phase: Completed; Phase 2

Conditions: Acute Respiratory Failure

Treatments: Drug: NaCl 0,9%,; Drug: Chlorhydrate de morphine

Study type: Interventional

Funder types: Other

Identifiers

NCT04358133

CRC18023

2019-003091-39 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 23 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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23 participants in 2 patient groups, including a placebo group

Chlorhydrate de morphine

Experimental group

Description:

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

Treatment:

Drug: Chlorhydrate de morphine

NaCl 0,9%

Placebo Comparator group

Description:

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

Treatment:

Drug: NaCl 0,9%,