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Trial registered on ANZCTR


Registration number
ACTRN12611000118909
Ethics application status
Approved
Date submitted
12/01/2011
Date registered
2/02/2011
Date last updated
15/03/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Does adjunctive therapy with Minocycline improve pain and opioid effectiveness in complex lower limb trauma? - A prospective randomised controlled trial.
Scientific title
Does adjunctive therapy with Minocycline improve pain and opioid effectiveness in complex lower limb trauma? - A prospective randomised controlled trial.
Secondary ID [1] 253394 0
Project No 404/10 Alfred Hospital Ethics Committee
Universal Trial Number (UTN)
U1111-1119-0238
Trial acronym
MILT trial
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Neuropathic Pain in Complex Lower Limb Trauma 260947 0
Opioid tolerance in Complex Lower Limb Trauma. 260948 0
Glial activation by opioids acting at TLR4 receptors in Complex Lower Limb Trauma. 260949 0
Condition category
Condition code
Injuries and Accidents 259086 259086 0 0
Fractures
Anaesthesiology 259225 259225 0 0
Pain management

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Minocycline 100 mg Twice daily (bd) introduced as soon as possible following trauma to lower limbs continued for 1 month. Minocycline may reduce the need for opioids which are normally used to treat severe pain caused by complex lower limb trauma.
Intervention code [1] 257840 0
Treatment: Drugs
Comparator / control treatment
Placebo which will be made using the same capsules as the minocycline but filled with a pharmacologically inert substance. The placebo medication will be produced in line with the placebo certificate of compliance. The placebo will be taken taken twice daily (bd) for one month.
Control group
Placebo

Outcomes
Primary outcome [1] 259938 0
Numerical Rating scale of pain (NRS) average of worst two pain scores in a 24 h period.
Timepoint [1] 259938 0
days 1, 3, 5, 7, 10, 14, day of discharge then one, three and six months.
Primary outcome [2] 259939 0
Leeds Assessment of Neuropathic Symptoms and Signs (LANNS)
Timepoint [2] 259939 0
days 1, 3, 5, 7, 10, 14, day of discharge then one, three and six months.
Secondary outcome [1] 268846 0
Opioid Use. Inpatient and outpatient opioid use will be converted to oral morphine equivalents as per the following reference;
Anderson R, Saiers J H, Abram S, Schlicht C. Accuracy in Equianalgesic Dosing:Conversion Dilemmas. Journal of Pain and Symptom Management. Vol. 21 No. 5 May 2001. 397-406
Timepoint [1] 268846 0
Inpatient use, discharge and at one, three and six months.
Secondary outcome [2] 273072 0
Brief Pain Inventory. (questionnaire)
Timepoint [2] 273072 0
At admission (or as soon as competent after admission), at discharge and at one, three and six months.
Secondary outcome [3] 273073 0
Profile of Moods States. (questionnaire)
Timepoint [3] 273073 0
At admission (or as soon as competent after admission), at discharge and at one, three and six months.
Secondary outcome [4] 273074 0
Pittsburgh Sleep Quality index. (questionnaire)
Timepoint [4] 273074 0
At admission (or as soon as competent after admission), at discharge and at one, three and six months.

Eligibility
Key inclusion criteria
1. Aged between 18 and 65 years. 2. Admitted to The Alfred Hospital Emergency and Trauma Centre (ET&C) with complex lower limb trauma. These fractures would include Distal Femur types A2/3, B2/3, C2/3. Proximal Tibia Types A3, B3, C1/2/3. Tibial Shaft Types B2/3 C1/2/3. Distal Tibia Types A3, B3, C2/3.(20) Simple fractures not specified above with substantial full thickness tissue loss or compartment syndrome requiring fasciotomy or substantial crush mechanism will also be included.3. Low probability of requirement for prolonged ventilation (> 72 hours) 4. Patient is conscious and able to give informed consent OR patient’s person responsible is able to give informed consent on behalf of the patient. 5. Average of worst two pain scores(NRS)preceeding 24 h >6
Minimum age
18 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Patients less than 18 years of age and greater than 65 years of age.
2. Death is imminent (less than 24 hours).
3. Patient not expected to survive 28 days because of an irreversible medical condition such as poorly controlled neoplasm or other end-stage disease.
4. Pregnant or breast feeding.
5. Patients with pre-burn psychiatric condition associated with psychotic or delusional symptomatology.
6. Patients with drug and alcohol dependence.
7. Patients with known hypersensitivity to minocycline or other tetracyclines.
8. Patients with known hypersensitivity to ketamine.
9. Patients with known hypersensitivity to pregabalin.
10. History of active persistent pain syndrome at time of admission
11. Opioid therapy in the two weeks preceding admission

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation by clinical trials pharmacist not involved in trial.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Random number generator
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Withdrawn
Reason for early stopping/withdrawal
Lack of funding/staff/facilities
Participant recruitment difficulties
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 258312 0
Charities/Societies/Foundations
Name [1] 258312 0
Australian And New Zealand College of Anaesthetists
Address [1] 258312 0
630 St Kilda Rd
Melbourne
Victoria 3004
Country [1] 258312 0
Australia
Primary sponsor type
Individual
Name
Dr David Lindholm
Address
The Alfred Hospital Pain Service
C/O Dept. Anaesthesia & Pain Medicine
PO BOX 315
Prahran Victoria 3181
Country
Australia
Secondary sponsor category [1] 257475 0
Individual
Name [1] 257475 0
Dr Patrick Mahar
Address [1] 257475 0
The Alfred Hospital Pain Service
C/O Dept. Anaesthesia & Pain Medicine
PO BOX 315
Prahran Victoria 3181
Country [1] 257475 0
Australia
Secondary sponsor category [2] 286712 0
Individual
Name [2] 286712 0
Dr Alex Konstantatos
Address [2] 286712 0
The Alfred
Commercial Rd Prahran
Victoria 3181
Country [2] 286712 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 260299 0
The Alfred Ethics Committee
Ethics committee address [1] 260299 0
PO Box 315
Prahran
Victoria 3181
Ethics committee country [1] 260299 0
Australia
Date submitted for ethics approval [1] 260299 0
16/12/2010
Approval date [1] 260299 0
22/12/2010
Ethics approval number [1] 260299 0
1/10/0404

Summary
Brief summary
Patients with complex lower limb trauma experience severe pain. Opioids and inflammation activate glia which may increase the severity of pain experienced. Minocycline acts via inhibiting Toll Like Receptor 4 and may reduce pain severity if given early. This and drugs with similar effects at TLR4 receptors appear to work well in animal models of severe pain. Minocycline may also reduce opioid tolerance and opioid side effects particularly respiratory depression.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 32085 0
Dr David Lindholm
Address 32085 0
Dept. of Anaesthesia and Pain Management
The Alfred Hospital
PO BOX 315
Prahran
Victoria
Australia 3181
Country 32085 0
Australia
Phone 32085 0
+61390763176
Fax 32085 0
Email 32085 0
d.lindholm@alfred.org.au
Contact person for public queries
Name 15332 0
Dr Dr David Lindholm
Address 15332 0
The Alfred Pain Unit
c/o Dept of Anaesthesia & Pain Medicine
PO BOX 315
Prahran Victoria 3181
Country 15332 0
Australia
Phone 15332 0
+61390763176
Fax 15332 0
+61390762813
Email 15332 0
d.lindholm@alfred.org.au
Contact person for scientific queries
Name 6260 0
Dr Patrick Mahar
Address 6260 0
The Alfred Pain Unit
c/o Dept of Anaesthesia & Pain Medicine
PO BOX 315
Prahran Victoria 3181
Country 6260 0
Australia
Phone 6260 0
+61390763176
Fax 6260 0
+61390762813
Email 6260 0
maharpatrick@hotmail.com; P.Mahar@alfred.org.au

No information has been provided regarding IPD availability
Summary results
No Results