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

• Sponsor: Assistance Publique - Hôpitaux de Paris (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT04358133
• Collaborator: (none)
• Enrollment: 22
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 18.1
• Patients Per Site Per Month: 1.2

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Respiratory Failure	Drug: Chlorhydrate de morphine; Drug: NaCl 0,9%,	Phase 2

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.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 22 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Randomized, double-blind, placebo-controlled, parallel-group,single center, phase 2 pilot studyRandomized, double-blind, placebo-controlled, parallel-group,single center, phase 2 pilot study
• Masking: Triple (Participant, Care Provider, Investigator)
• 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
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Dec 16, 2020
• Anticipated Primary Completion Date: Jun 19, 2022
• Anticipated Study Completion Date: Jun 19, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Chlorhydrate de morphine initial dose of 2 mg, followed by 1 mg every 3 minutes until a VAS-dyspnea <40 then relay subcut	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
Placebo Comparator: NaCl 0,9% initial dose of 2 mg, followed by 1 mg every 3 minutes until a VAS-dyspnea <40 then relay subcut	Drug: NaCl 0,9%,; The control group will receive placebo NaCl 0.9% administered according to the same protocol as the experimental arm

Outcome Measures

Primary Outcome Measures

1. Average dyspnea over 24 hours [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 Outcome Measures

1. Intensity of dyspnea [every 4 hours over 24 hours]

   patient reported outcome measure (PRO) ; min=0;max=100(worse)

2. Incidence of severe dyspnea (dyspnea ≥40) [within 24 hours]

   patient reported outcome measure (PRO) ; min=0;max=100(worse)

3. Anxiety [every 4 hours as well as over the first 24 hours]

   Patient reported outcome measure (PRO) ; min=0;max=100(worse)

4. Incidence of moderate to severe anxiety [every 4 hours over 24 hours]

   Incidence of moderate to severe anxiety (PRO) ; min=0;max=100(worse)

5. Intubation rate [within the first 48 hours]

   Intubation rate

6. Vigilance level (Glasgow Coma Scale : impaired alertness defined by Glasgow Coma Scale ≤ 12) [every 4 hours as well as the first 48 hours]

   Vigilance level ; GCS : min=3(worse) ;max=15

7. Incidence of coma [within the first 48 hours]

   Incidence of coma

8. Incidence of delirium [within the first every 4 hours as well as over the first 48 hours]

   Incidence of delirium

9. Respiratory rate [every 4 hours as well as over the first 24 hours]

   Respiratory rate

10. Proportion of patients requiring the transition from one oxygenation technique to another [At the end of the study (12 months)]

    Proportion of patients requiring the transition from one oxygenation technique to another

11. Intensity of pain [every 4 hours]

    Patient reported outcome measure (PRO) ; min=0;max=100(worse)

12. Duration of night sleep the first night [at the end of the first night]

    Duration of night sleep the first night (number of hours)

13. Quality of sleep the first night [at the end of the first night]

    Patient reported outcome measure (PRO); min=0;max=100(worse)

14. Severity of dry eye [in the first 24 hours]

    Patient reported outcome criteria (PRO); min=0;max=100(worse)

15. Severity of dry nose [in the first 24 hours]

    Patient reported outcome criteria (PRO); min=0;max=100(worse)

16. Severity of feeling of gastric distension [in the first 24 hours]

    Patient reported outcome criteria (PRO); min=0;max=100(worse)

17. Constipation [in the first 48 hours]

    Constipation (PRO); min=0;max=100(worse)

18. Nausea [in the first 48 hours]

    Patient reported outcome criteria (PRO) ;min=0;max=100(worse)

19. Nurses' adherence to the protocol [in the first 24 hours]

    Nurses' adherence to the protocol (questionnaire)

20. Nurses' satisfaction with the protocol [in the first 24 hours]

    Nurses' satisfaction with the protocol (questionnaire)

21. Number of non invasive ventilation sessions [in the first 24 hours]

    Number of non invasive ventilation sessions

22. Total duration of non invasive ventilation [in the first 24 hours]

    Total duration of non invasive ventilation (number of hours)

23. Tolerance of non invasive ventilation [in the first 24 hours]

    Tolerance of non invasive ventilation (PRO) ;min=0;max=100(worse)

24. Duration of HFNCO (high-flow nasal canula oxygenation) [in the first 24 hours]

    Duration of HFNCO (number of hours)

25. Tolerance of HFNCO(high-flow nasal canula oxygenation) [in the first 24 hours]

    Tolerance of HFNCO : number of adverses events

26. Duration of standard oxygen [in the first 24 hours]

    Duration of standard oxygen (number of hours)

27. Tolerance of standard oxygen [in the first 24 hours]

    Tolerance of standard oxygen : number of adverses events

28. Any adverse or serious event occurring [within the first 48 hours]

    Any adverse or serious event occurring

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Groupe Hospitalier Pitié Salpetriere	Paris		France	75013

Sponsors and Collaborators

• Assistance Publique - Hôpitaux de Paris

Investigators

• Study Director: Alexandre DEMOULE, PH, Assistance Publique - Hôpitaux de Paris

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Assistance Publique - Hôpitaux de Paris
• ClinicalTrials.gov Identifier: NCT04358133
• Other Study ID Numbers: CRC18023; 2019-003091-39
• First Posted: Apr 24, 2020
• Last Update Posted: Jan 25, 2022
• Last Verified: Jan 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Assistance Publique - Hôpitaux de Paris: Acute respiratory failure; Dyspnea; Opioids; Comfort; Intensive care unit
• Additional relevant MeSH terms: Respiratory Insufficiency; Dyspnea; Respiratory Distress Syndrome; Morphine

Study Results

No Results Posted as of Jan 25, 2022