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

Sponsor

Mundipharma Pharmaceuticals S.L. (Industry)

Overall Status

Completed

CT.gov ID

NCT03256903

Collaborator

Spanish Society for Emergency Medicine (SEMES) (Other), Spanish Clinical Research Network - SCReN (Other)

310

Enrollment

Locations

Arms

12.8

Actual Duration (Months)

22.1

Patients Per Site

1.7

Patients Per Site Per Month

Study Details

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

Actual Enrollment :

310 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Phase IIIb open randomized clinical trialPhase 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 :

Jul 7, 2017

Actual Primary Completion Date :

Mar 6, 2018

Actual Study Completion Date :

Jul 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 Names: 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 Names: No other 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 Names:

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 Names:

No other interventions

Outcome Measures

Primary Outcome Measures

Pain relief [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)
Analgesia effectiveness [Change from baseline to 3, 5, 10, 15, 20 and 30 min]
Difference between arms related to analgesia effectiveness
Analgesia speed of action [From time of randomization up to 20 minutes]
Difference between arms related to speed of action of analgesia for all patients
Safety for patients with severe pain, treated with second or third step analgesics [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
Patient-averaged summed pain intensity difference 15 min after STA [from baseline to 3, 5, 10 and 15 minutes post dose]
Patient-averaged summed pain intensity difference 15 min after STA
Pain Responders [from baseline to 20 minutes post dose]
Pain Responders (with >30% pain relief compared to baseline) at 20 min

Secondary Outcome Measures

Investigators and patients satisfaction [30 min from start of administration]
Investigators and patients satisfaction measured as convenience, treatment efficacy and adverse events, using NRS scales (0-10)
Patient and investigators' fulfillment of expectations [30 min from start of administration]
Patient and investigators' fulfillment of expectations, measured with a 5 items Likert scale
Patients' Global Impression of Change with the treatments [Up until 30 minutes from STA]
Patients' Global Impression of Change with the treatments, measured using a 7 items Likert scale
Treatment cost of pain relief [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
Safety rates of treatment emergent adverse events [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

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

	Site	City	State	Country	Postal Code
1	Hospital de Viladecans	Viladecans	Barcelona	Spain	08840
2	Hospital del Bierzo	Ponferrada	León	Spain	24404
3	Hospital Asepeyo Coslada	Coslada	Madrid	Spain	28823
4	Hospital Puerta de Hierro	Majadahonda	Madrid	Spain	28222
5	Hospital Álvaro Cunqueiro	Vigo	Pontevedra	Spain	36312
6	Hospital Gernika-Lumo	Gernika-Lumo	Vizcaya	Spain	48300
7	Hospital General de Alicante	Alicante		Spain	03010
8	Hospital Universitario La Princesa	Madrid		Spain	28006
9	Hospital Clínico San Carlos	Madrid		Spain	28040
10	SUMMA - Comunidad de Madrid	Madrid		Spain	28045
11	Hospital La Paz	Madrid		Spain	28046
12	Hospital Virgen del Rocío	Sevilla		Spain	41013
13	Hospital Campo Grande	Valladolid		Spain	47006
14	Complejo Asistencial de Zamora	Zamora		Spain	49022