MIdazolam Versus MOrphine in Acute Pulmonary Edema (MIMO Trial)

• Sponsor: Alberto Dominguez-Rodriguez (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02856698
• Collaborator: (none)
• Enrollment: 111
• Locations: 8
• Arms: 2
• Actual Duration (Months): 44.8
• Patients Per Site: 13.9
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

Acute pulmonary edema (APE) is a common condition in the emergency room, associated with considerable mortality. The use of intravenous morphine in the treatment of APE remains controversial and Benzodiazepines have been suggested as an alternative for morphine to relieving dyspnoea and anxiety in the patients with APE. The MIdazolan versus MOrphine in APE trial (MIMO) is a multicenter, prospective, open-label, randomized study designed to evaluate the efficacy and safety of morphine in patients with APE.

Condition or Disease	Intervention/Treatment	Phase
Acute Pulmonary Edema	Drug: Midazolam; Drug: Morphine	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 111 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Study Design and Rationale of "A Multicenter, Open-Labeled, Randomized Controlled Trial Comparing MIdazolam Versus MOrphine in Acute Pulmonary Edema": MIMO Trial
• Actual Study Start Date: Apr 8, 2017
• Actual Primary Completion Date: Dec 31, 2020
• Actual Study Completion Date: Dec 31, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: midazolam The dose of midazolam intravenously will be of 1 mg which may be repeated until a total dose of 3 mg.	Drug: Midazolam; Dose use according to the product technical sheet
Active Comparator: morphine The dose of morphine intravenously is of 2-4 mg which may be repeated until a total dose of 8 mg if the patient continue suffering from severe anxiety or distress caused by APE	Drug: Morphine; Dose use according to the product technical sheet

Outcome Measures

Primary Outcome Measures

1. In-hospital Mortality [28 days after of the hospitalization]

   In hospital mortality

Secondary Outcome Measures

1. Number of Participants That Required Invasive Mechanical Ventilation [Up to 1 week]

2. Length of Hospital Stay [Up to 30 days]

   Length of hospital stay

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients with acute pulmonary edema with dyspnoea and anxiety

Exclusion Criteria:

• Patients with known severe liver disease.

• Patients with known severe renal disease.

• Patients with expectation of death from other illness during the course of the trial.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hospital Universitario Reina Sofía de Córdoba	Córdoba	Andalucía	Spain
2	Hospital Comarcal de la Axarquía	Málaga	Andalucía	Spain
3	Hospital Clínic i Provincial de Barcelona	Barcelona	Cataluña	Spain
4	Hospital Universitario de Canarias	La Laguna	Santa Cruz De Tenerife	Spain	38320
5	Hospital General de Alicante	Alicante		Spain
6	Hospital Clínico Universitario San Carlos	Madrid		Spain
7	Hospital General Universitario Reina Sofía	Murcia		Spain	30003
8	Hospital Comarcal de Axarquia	Málaga		Spain

Sponsors and Collaborators

• Alberto Dominguez-Rodriguez

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Jul 7, 2016
• Statistical Analysis Plan - May 26, 2021

More Information

Publications

None provided.

• Responsible Party: Alberto Dominguez-Rodriguez, Alberto Domínguez- Rodríguez, MD, PhD, FESC, Hospital Universitario de Canarias
• ClinicalTrials.gov Identifier: NCT02856698
• Other Study ID Numbers: EUDRACT: 2016-000884-17
• First Posted: Aug 5, 2016
• Last Update Posted: Jun 9, 2022
• Last Verified: May 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Alberto Dominguez-Rodriguez, Alberto Domínguez- Rodríguez, MD, PhD, FESC, Hospital Universitario de Canarias: Acute heart failure; morphine; midazolam; in-hospital mortality
• Additional relevant MeSH terms: Pulmonary Edema; Edema; Midazolam; Morphine

Study Results

Participant Flow

Recruitment Details	The recruitment period goes from 08/04/2017 to 30/12/2020

Arm/Group Title	Midazolam	Morphine
Arm/Group Description	The dose of midazolam intravenously will be of 1 mg which may be repeated until a total dose of 3 mg. Midazolam: Dose use according to the product technical sheet	The dose of morphine intravenously is of 2-4 mg which may be repeated until a total dose of 8 mg if the patient continue suffering from severe anxiety or distress caused by APE Morphine: Dose use according to the product technical sheet
Period Title: Overall Study
STARTED	55	56
COMPLETED	48	46
NOT COMPLETED	7	10

Baseline Characteristics

Arm/Group Title	Midazolam	Morphine	Total
Arm/Group Description	The dose of midazolam intravenously will be of 1 mg which may be repeated until a total dose of 3 mg. Midazolam: Dose use according to the product technical sheet	The dose of morphine intravenously is of 2-4 mg which may be repeated until a total dose of 8 mg if the patient continue suffering from severe anxiety or distress caused by APE Morphine: Dose use according to the product technical sheet	Total of all reporting groups
Overall Participants	55	56	111
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	9 16.4%	7 12.5%	16 14.4%
>=65 years	46 83.6%	49 87.5%	95 85.6%
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	78.4	79.9	79.15
Sex: Female, Male (Count of Participants)
Female	28 50.9%	30 53.6%	58 52.3%
Male	27 49.1%	26 46.4%	53 47.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	55 100%	56 100%	111 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	In-hospital Mortality
Description	In hospital mortality
Time Frame	28 days after of the hospitalization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Midazolam	Morphine
Arm/Group Description	The dose of midazolam intravenously will be of 1 mg which may be repeated until a total dose of 3 mg. Midazolam: Dose use according to the product technical sheet	The dose of morphine intravenously is of 2-4 mg which may be repeated until a total dose of 8 mg if the patient continue suffering from severe anxiety or distress caused by APE Morphine: Dose use according to the product technical sheet
Measure Participants	55	56
Count of Participants [Participants]	7 12.7%	10 17.9%

2. Secondary Outcome

Title	Number of Participants That Required Invasive Mechanical Ventilation
Time Frame	Up to 1 week

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Midazolam	Morphine
Arm/Group Description	The dose of midazolam intravenously will be of 1 mg which may be repeated until a total dose of 3 mg. Midazolam: Dose use according to the product technical sheet	The dose of morphine intravenously is of 2-4 mg which may be repeated until a total dose of 8 mg if the patient continue suffering from severe anxiety or distress caused by APE Morphine: Dose use according to the product technical sheet
Measure Participants	55	56
Number [participants]	3 5.5%	1 1.8%

3. Secondary Outcome

Title	Length of Hospital Stay
Description	Length of hospital stay
Time Frame	Up to 30 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Midazolam	Morphine
Arm/Group Description	The dose of midazolam intravenously will be of 1 mg which may be repeated until a total dose of 3 mg. Midazolam: Dose use according to the product technical sheet	The dose of morphine intravenously is of 2-4 mg which may be repeated until a total dose of 8 mg if the patient continue suffering from severe anxiety or distress caused by APE Morphine: Dose use according to the product technical sheet
Measure Participants	55	56
Median (Inter-Quartile Range) [days]	7	6

Adverse Events

Time Frame	The adverse events were collected through study completion (1 year)
Adverse Event Reporting Description	The adverse events observed were related to the circulatory, respiratory, and other systems (nervous, endocrine and renal).
Arm/Group Title	Midazolam		Morphine
Arm/Group Description	The dose of midazolam intravenously will be of 1 mg which may be repeated until a total dose of 3 mg. Midazolam: Dose use according to the product technical sheet		The dose of morphine intravenously is of 2-4 mg which may be repeated until a total dose of 8 mg if the patient continue suffering from severe anxiety or distress caused by APE Morphine: Dose use according to the product technical sheet
All Cause Mortality
	Midazolam		Morphine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/55 (16.4%)		13/56 (23.2%)
Serious Adverse Events
	Midazolam		Morphine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/55 (18.2%)		24/56 (42.9%)
Cardiac disorders
ischemic stroke	10/55 (18.2%)	10	24/56 (42.9%)	24
Other (Not Including Serious) Adverse Events
	Midazolam		Morphine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/55 (0%)		0/56 (0%)

Limitations/Caveats

The main limitation of the study was that the study treatment, because it was a serious pathology, was sometimes administered in the ambulance, before admission to the hospital emergency room. Another limitation has been the COVID-19 pandemic

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.