Primary Objective: This study aims at evaluating efficacy (in terms of superiority to) of low-dose methoxyflurane versus standard of care in the treatment of acute pain due to extremity injuries in the emergency medical services in the Netherlands.…
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
pijn ten gevolge van trauma
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Change in mean pain intensity (NRS) over 10 min:
Change from baseline (t=0; first *in study* pain (NRS) assessment on scene) to
3, 5 and 10 min using Mixed-Effect Model Repeated Measure (MMRM).
Secondary outcome
Change in mean pain intensity (NRS) over 5 min
Change from baseline (t=0; first in study pain (NRS) assessment on scene), to 3
and 5 min using Mixed-Effect Model Repeated Measure (MMRM).
Speed of onset of analgesia
Time from ambulance arrival to first clinically relevant pain relief (*30%
reduction calculated from baseline (t=0; first in study pain (NRS) assessment
on scene, 3, 5 and 10 min pain (NRS) measurements). Time is calculated from
reported arrival time and reported time of pain measurements.
Proportion of patients with a clinically meaningful reduction in pain intensity
score
Evaluation of the proportion of patients with a clinically meaningful reduction
in pain NRS-score (NRS>30% pain relief compared to baseline) at 10 minute
calculated from baseline (t=0 first in study pain (NRS) assessment on scene)
and t=10 min pain (NRS) measurements.
Satisfaction regarding convenience, treatment efficacy and adverse events
Patients*and Investigator*s satisfaction regarding convenience, treatment
efficacy and adverse events will be measured using a 7-item Likert scale in
which the respondent will be asked to evaluate the medication administered
after 10 min.
Fulfilment of expectations
Patient and investigators* fulfilment of expectations will be measured with a
5-items Likert scale after 10 min.
Patients*Global Impression of Change
Patients* Global Impression of Change with the treatment at discharge time will
be measured using a 7-items Likert scale after 10 min.
Treatment costs of pain relief
Standard treatment cost of pain relief will be calculated. A calculation will
be made calculating the cost of a 1-point reduction in pain NRS score and the
costs of obtaining clinically relevant pain relief (30% reduction in pain NRS
score) will be calculated in both arms.
Health care resource consumption will be measured considering e.g. use of
medication, materials, use of monitoring, on scene time as well as
transportation costs. Use of materials, medication and monitoring, as well as
on scene time and transportation will be based on patient records.
Safety
All AEs and ADRs reported from verbal consent to end of follow up for IMP and
SoC treatment unless, in the opinion of the investigator or designated
physician, the AE constitute components of the underlying injury. Patients will
be asked to document AEs or ADRs of the IMP or SoC treatment in a patient diary
for the 14 day post-dose period.
Background summary
The prevalence of trauma pain is high and if untreated, trauma pain may have a
great burden on the patient and result in unnecessary stress and suffering. The
stress response to
prolonged pain can cause the appearance of unwanted psychological and
physiological events that may interfere with the healing process and prolong
patient recovery. Therefore, it is of utmost importance that the effective
analgesia is quickly administered, in order to maximise patient satisfaction
and recovery and to improve the chances of quicker patient discharge1-4,6
Desirable characteristics for an analgesic in pre-hospital and emergency care
are: rapid onset of analgesia, sufficient duration of action, good tolerability
and few side effects; efficacy for many different kinds or pain in different
populations; ease of storage and administration; and the ability of the patient
to self-administer and control the dose. Unlike other available analgesic
choices, low-dose methoxyflurane possesses many of these desirable
characteristics, as it is rapidly acting, can last for up to an hour if inhaled
intermittently or around 20-30 minutes if inhaled continuously. Furthermore, it
provides effective analgesia for different kinds of trauma pain, causes few
side effects, is small and simple to use/store, and the patient is able to
control the dose administered7.
Despite the fact that low-dose methoxyflurane has been marketed in Australia
and New Zealand for the treatment of emergency pain due to trauma for over 40
years, no randomized clinical trials in the emergency medical services (EMS)
evaluating its analgesic effectiveness compared to standard of care have been
published.
This study however, will be the first study comparing the analgesic efficacy of
low-dose methoxyflurane with standard of care in emergency medical services in
the Netherlands.
In the Netherlands most used painkillers in the EMS are IV paracetamol, IN/IV
fentanyl and IV ketamine. This study will establish the efficacy of low-dose
methoxyflurane compared with current standard of care in the Dutch Emergency
Medical Services.
Study objective
Primary Objective: This study aims at evaluating efficacy (in terms of
superiority to) of low-dose methoxyflurane versus standard of care in the
treatment of acute pain due to extremity injuries in the emergency medical
services in the Netherlands.
Secondary Objective(s): Evaluating the analgesic effectiveness (proportion of
patients with a clinically relevant reduction of the pain score), speed of
onset of analgesia, ease of use, time on scene, transportation costs and safety
Study design
Randomized, open label*, controlled trial in the emergency medical services.
*It is not possible to arrange a double-blind study, due to control arm
(Standard of Care (SoC)). Within SoC there are multiple treatment options that
can be adapted to the situation on scene.
Intervention
Low-dose MEOF:
Patients will be supplied with an inhaler containing 3 mL low-dose MEOF,
(99.9%) The trained Emergency Medical Services nurse of the dedicated research
team will train the patient to self-administer MEOF.
Study burden and risks
Low-dose methoxyflurane has been administered as an analgesic for over 30 years
in Australia and is currently approved for marketing in over 15 countries
worldwide, including Australia, New-Zealand, and the majority of Europe. In the
majority of Europe it has been approved for the emergency relief of moderate to
severe pain in conscious adult patients with trauma and associated pain.
Serious dose-related nephrotoxicity has only been associated with
methoxyflurane when used in high doses over prolonged periods during general
anaesthesia. No nephrotoxicity has been observed following methoxyflurane when
used under currently approved low-dose.
Therefore for use within the approved indication and in this study setting in
line with the approved indication, it is estimated that the risk of treatment
is limited.
The patient has the benefit of obtaining effective patient controlled analgesia
for different kinds of trauma pain with a rapid-acting non-opioid. Furthermore,
MEOF causes few side effects and is small and simple to use/store. The overall
benefit for health care is the collection of more clinical data evaluating the
place and role of low-dose methoxyflurane as first-line analgesic and compare
it with current standard treatment protocols in the Emergency Medical Services.
Leusderend 24
Leusden 3832 RC
NL
Leusderend 24
Leusden 3832 RC
NL
Listed location countries
Age
Inclusion criteria
1. Patients should be * 18 years of age and competent to participate in the
study according to the Investigator*s opinion.
2. Moderate pain (NRS0-10 *4 and *8) secondary to extremity injuries
3. Conscious patients with a stable circulation
Exclusion criteria
A potential subject who meets any of the defined criteria will not be eligible
for participation in this study and will be treated according to SoC. These
criteria will be judged by the Investigator prior to study participation and
will be based on (hetero)anamnesis. The defined criteria are:
1. Known hypersensitivity to MEOF or any fluorinated anaesthetic.
2. Personal or family history of malignant hyperthermia.
3. Patients with known liver disease and patients who have a history of showing
signs of liver damage after previous MEOF use or halogenated hydrocarbon
anaesthesia
4. Known clinically significant renal impairment
5. Known pregnant or likely to be pregnant women at the time of inclusion.
6. Clinically evident cardiovascular instability
7. Clinically evident respiratory depression
8. Treatment with analgesia (with the exception of oral WHO-step 1 analgesics)
prior to arrival of the EMS to reduce pain caused by the trauma.
9. Altered level of consciousness due to any cause, including head injury,
drugs or al-cohol
10. Active alcohol or drug abuse and/or history of opioid abuse
11. Degenerative diseases, mental illness or other conditions that could affect
ability of valuing pain intensity
12. Patients unable to understand the purpose of the study and perform
self-assessments, following investigator*s criteria.
13. Participation in another clinical trial within 30 days prior to
randomization.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2018-001601-82-NL |
| CCMO | NL65859.028.18 |