Methoxyflurane vs Standard Analgesic Treatment for Trauma Pain in Spanish Emergency Units (InMEDIATE)

• ClinicalTrials.gov Identifier: NCT03256903
• Recruitment Status: Completed
• First Posted: August 22, 2017
• Last Update Posted: August 20, 2018
• Sponsor: Mundipharma Pharmaceuticals S.L.
• Collaborators: Spanish Society for Emergency Medicine (SEMES); Spanish Clinical Research Network - CAIBER
• Information provided by (Responsible Party): Alberto M. Borobia, Hospital Universitario La Paz

Study Description

Brief Summary:

Clinical trial to compare pain relief between methoxyflurane and any analgesic treatment used in usual clinical practice, in patients with trauma and associated pain, treated in Spanish emergency units.

Condition or disease	Intervention/treatment	Phase
Acute Pain Due to Trauma	Drug: Methoxyflurane; Drug: Standard of care	Phase 3

Detailed Description:

Open, randomized clinical trial to compare emergency pain relief between methoxyflurane and standard of care in patients with trauma and associated pain, treated in Spanish emergency units.

Methoxyflurane is a fluorinated ethyl methyl ether, with the chemical name 2:2-dichloro-1:1-difluoroethyl methyl ether. It belongs to the fluorinated hydrocarbon group of volatile anaesthetics. It is inhaled as a vapour at low (sub-anaesthetic) concentrations to achieve an analgesic effect for the management of pain.

In Europe countries, where methoxyflurane is already marketed, it is indicated for emergency relief of moderate to severe pain in conscious adult patients with trauma and associated pain.

On the other hand, current clinical practice includes a variety of analgesic agents, with the choice of which to employ based on consideration of the risk-benefit factors of each class of drug, as well as the type of pain, its severity, and the risk of adverse effects.

The main objective of this study is to assess Methoxyflurane's significant advantage in terms of anaglesic effectiveness, as it is known as a rapidly acting, non-narcotic analgesic for the treatment of emergency pain.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 310 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Phase IIIb open randomized clinical trial
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Open Randomized Clinical Trial to Compare Pain Relief Between Methoxyflurane and Standard of Care for Treating Patients With Trauma Pain in Spanish Emergency Units.
• Actual Study Start Date: July 7, 2017
• Actual Primary Completion Date: March 6, 2018
• Actual Study Completion Date: July 31, 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: Methoxyflurane; Patients will be supplied with up to two inhalers containing 3 mL methoxyflurane. A member of the research team will train the patient to self-administer methoxyflurane	Drug: Methoxyflurane; Up to two inhalers containing 3 mL methoxyflurane. Treatment duration: 1 administration in 1 day.; Other Name: No other interventions
Active Comparator: Standard of Care (SoC); Patients will be treated following standard of care (SoC) of the hospital, for emergency relief of trauma and associated pain. Any kind of analgesia administered by any route will be valid. Only administration of one analgesic (or fixed combinations) at baseline will considered SoC. Other required analgesics will be considered rescue medication.	Drug: Standard of care; Any kind of analgesia, administered by any route for emergency relief of moderate to severe pain in conscious adult patients with trauma and associated pain; Other Name: No other interventions

Outcome Measures

Primary Outcome Measures :

1. Pain relief [ Time Frame: At baseline, 3, 5, 10, 15 and 20 minutes from STA ]
   Change in mean pain intensity over 20 min from start of administration (STA) and time to first pain relief, measured by numeric scale (0-10)
2. Analgesia effectiveness [ Time Frame: Change from baseline to 3, 5, 10, 15, 20 and 30 min ]
   Difference between arms related to analgesia effectiveness
3. Analgesia speed of action [ Time Frame: From time of randomization up to 20 minutes ]
   Difference between arms related to speed of action of analgesia for all patients
4. Safety for patients with severe pain, treated with second or third step analgesics [ Time Frame: Up until 14 days from STA ]
   Difference between arms related to safety for patients with severe pain (NRS >7), treated with second or third step analgesics
5. Patient-averaged summed pain intensity difference 15 min after STA [ Time Frame: from baseline to 3, 5, 10 and 15 minutes post dose ]
   Patient-averaged summed pain intensity difference 15 min after STA
6. Pain Responders [ Time Frame: from baseline to 20 minutes post dose ]
   Pain Responders (with >30% pain relief compared to baseline) at 20 min

Secondary Outcome Measures :

1. Investigators and patients satisfaction [ Time Frame: 30 min from start of administration ]
   Investigators and patients satisfaction measured as convenience, treatment efficacy and adverse events, using NRS scales (0-10)
2. Patient and investigators' fulfillment of expectations [ Time Frame: 30 min from start of administration ]
   Patient and investigators' fulfillment of expectations, measured with a 5 items Likert scale
3. Patients' Global Impression of Change with the treatments [ Time Frame: Up until 30 minutes from STA ]
   Patients' Global Impression of Change with the treatments, measured using a 7 items Likert scale
4. Treatment cost of pain relief [ Time Frame: Up until 60 minutes from randomization ]
   Treatment cost of pain relief, measured considering use of fungible material; need of nurse to administer iv treatments; time to discharge
5. Safety rates of treatment emergent adverse events [ Time Frame: Up until 14 days from STA ]
   Safety rates of treatment emergent adverse events (TEAE) in both arms, including alterations in biochemical and blood count.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Adult patients: ≥ 18 years of age
• Moderate to severe pain (NRS 0-10; >=4) secondary to trauma
• Without anticipating surgery due to the trauma, requiring hospitalization (hospital stay 12h)
• Conscious patient.
• Giving informed consent in writing

Exclusion Criteria:

• Hypersensitivity to methoxyflurane (MEOF) or any fluorinated anaesthetic.
• Malignant hyperthermia: patients with known or genetically susceptible to malignant hyperthermia or a history of severe adverse reactions in either patient or relatives.
• Patients who have a history of showing signs of liver damage after previous MEOF use or halogenated hydrocarbon anaesthesia
• Known clinically significant renal impairment
• Known pregnant or likely to be pregnant women at the time of inclusion.
• Clinically evident cardiovascular instability
• Clinically evident respiratory depression
• Patients taken any analgesic for the traumatic pain before inclusion
• Altered level of consciousness due to any cause, including head injury, drugs or alcohol
• Degenerative diseases, mental illness or other conditions that could affect ability of valuing pain intensity
• Patients to be unable to understand the purpose of the study and perform self-assessments, following investigator's criteria.
• Participation in another clinical trial within 30 days prior to randomization

Contacts and Locations

Locations

Spain

Hospital de Viladecans

Viladecans, Barcelona, Spain, 08840

Hospital del Bierzo

Ponferrada, León, Spain, 24404

Hospital Asepeyo Coslada

Coslada, Madrid, Spain, 28823

Hospital Puerta de Hierro

Majadahonda, Madrid, Spain, 28222

Hospital Álvaro Cunqueiro

Vigo, Pontevedra, Spain, 36312

Hospital Gernika-Lumo

Gernika-Lumo, Vizcaya, Spain, 48300

Hospital General de Alicante

Alicante, Spain, 03010

Hospital Universitario La Princesa

Madrid, Spain, 28006

Hospital Clínico San Carlos

Madrid, Spain, 28040

SUMMA - Comunidad de Madrid

Madrid, Spain, 28045

Hospital La Paz

Madrid, Spain, 28046

Hospital Virgen del Rocío

Sevilla, Spain, 41013

Hospital Campo Grande

Valladolid, Spain, 47006

Complejo Asistencial de Zamora

Zamora, Spain, 49022

Sponsors and Collaborators

Mundipharma Pharmaceuticals S.L.

Spanish Society for Emergency Medicine (SEMES)

Spanish Clinical Research Network - CAIBER

Investigators

• Study Director: Alberto Borobia, MD, PhD; La Paz University Hospital

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Borobia AM, Collado SG, Cardona CC, Pueyo RC, Alonso CF, Torres IP, González MC, Casal Codesido JR, Betegón MA, Barcela LA, Andicoechea AO, Testa AF, Colina JT, Dorribo AC, Del Arco Galán C, Martínez Ávila JC, Lugilde ST, Carcas Sansuán AJ; InMEDIATE Investigators Group. Inhaled Methoxyflurane Provides Greater Analgesia and Faster Onset of Action Versus Standard Analgesia in Patients With Trauma Pain: InMEDIATE: A Randomized Controlled Trial in Emergency Departments. Ann Emerg Med. 2020 Mar;75(3):315-328. doi: 10.1016/j.annemergmed.2019.07.028. Epub 2019 Oct 14.

• Responsible Party: Alberto M. Borobia, MD, PhD, Hospital Universitario La Paz
• ClinicalTrials.gov Identifier: NCT03256903
• Other Study ID Numbers: MR311-3502
• First Posted: August 22, 2017
• Last Update Posted: August 20, 2018
• Last Verified: August 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Alberto M. Borobia, Hospital Universitario La Paz:

Methoxyflurane; emergency; trauma pain; inhaled analgesia

Additional relevant MeSH terms:

Emergencies; Acute Pain; Wounds and Injuries; Disease Attributes; Pathologic Processes; Pain; Neurologic Manifestations; Methoxyflurane; Anesthetics, Inhalation; Anesthetics, General; Anesthetics; Central Nervous System Depressants; Physiological Effects of Drugs