Plain English Summary
Background and study aims
Osteoarthritis is a condition that causes joints to become painful and stiff. When it affects the hip it can be treated with a hip replacement, where the damaged joint is replaced with an artificial one. Continued pain after surgery is a real health care problem. Excessive inflammation, the immune system, and the opioid receptors on the surface of the immune cells seem to have a central role. Although opioid drugs are usually used after surgery, the best treatment is not yet known. The aim of this study is to find out whether immune cells’ opioid receptors could be used as markers to prevent chronic pain and opioid tolerance/addiction after hip replacement surgery.
Who can participate?
Patients aged 18 and over undergoing hip replacement surgery
What does the study involve?
Participants are randomly allocated to be treated with either tapentadol (an opioid drug) at one of two doses, or NonSteroidal Anti-Inflammatory Drugs (NSAIDs)/paracetamol. All groups follow the allocated plan for 30 days before surgery and 15 days after (if the patient feels pain). For each group, blood samples are collected before, during and up to 60 days after surgery in order to assess the immune cells’ opioid receptor levels.
What are the possible benefits and risks of participating?
Patients may benefit from an easy and non-invasive diagnostic test. Patients won't be overloaded by clinical tests and will be enlisted during routine clinical visits, limiting anxiety, stress, social problems and costs. The main risk could be the tolerance and/or addiction to opioids. The results of this study could be used to tailor treatment to prevent tolerance and/or addiction from occurring.
Where is the study run from?
Policlinico Tor Vergata (Italy)
When is study starting and how long is it expected to run for?
May 2016 to November 2017
Who is funding the study?
ISAL Foundation (Italy)
Who is the main contact?
1. Prof. William Raffaeli
wraffaeli@yahoo.it
2. Dr Valentina Malafoglia
valentinamalafoglia@yahoo.it
Trial website
Contact information
Type
Scientific
Primary contact
Prof William Raffaeli
ORCID ID
http://orcid.org/0000-0003-0240-8993
Contact details
Via San Salvador 204
Torre Pedrera
47922
Italy
+39 (0)541 725166
wraffaeli@yahoo.it
Type
Scientific
Additional contact
Dr Valentina Malafoglia
ORCID ID
http://orcid.org/0000-0002-1533-704X
Contact details
Via San Salvador 204
Torre Pedrera
47922
Italy
+39 (0)541 725166
valentinamalafoglia@yahoo.it
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
N/A
Study information
Scientific title
An interventional, double-blind randomized parallel-group, phase IV study for the assessment of a tailored Opioid therapy and osteoarthritic chronic pain bioMarkers, to improve Arthoprosthesis patients rehabilitation (OpMarkArt)
Acronym
OpMarkArt (Opioids-Markers-Arthroprosthesis)
Study hypothesis
The trialists hypothesize that a pre-surgery opioid tailored therapy could modulate lymphocytes opioid receptors and the onset of postoperative osteoarthritic chronic pain. Thus, the trialists propose opioid receptors in the surface of lymphocytes as biological diagnostic markers in order to analyze chronic pain predisposition/evolution and opioids addiction/tolerance insurgence.
Ethics approval
Institutional independent ethics committee of Policlinico Tor Vergata (Rome), 28/06/2016, ref: 110/16
Study design
Interventional multicentre double-blind randomized parallel-group phase IV study
Primary study design
Interventional
Secondary study design
Randomised parallel trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details to request a patient information sheet
Condition
Total hip arthroplasty for osteoarthritis or aseptic necrosis of the femoral head
Intervention
60 patients undergoing hip surgery will be enrolled in a randomized phase IV study. Patients will be randomised in a double-blind manner into three medication arms administered in common practice. Randomisation will be performed using a computational approach, based on a single sequence of random assignments (simple randomization). Patients and their medical doctors will be blind to the assigned treatment. Each arm involves 20 patients:
1. Tapentadol 25mg x 2 die
2. Tapentadol 75mg x 2 die
3. NSAIDs/paracetamol in accordance with surgeon’s custom
All the arms will follow the specific pharmacological plan for 30 days before surgery and 15 days after (if the patient feels pain). Each patient will be subjected to five blood sample collections at precise time points: the day of enrolment and starting therapy (T0); the 30th day of therapy, coinciding with the moment of surgery (T2); the day after surgery (T3); 30 days after surgery (T4); 60 days after surgery, in correspondence with the final assessment and follow up (T5). T1 coincides with clinical examination, 15 days after the enrolment, without any blood collection.
On the day of surgery, patients will be monitored with standard practices, such as electrocardiogram, oxygen saturation, invasive and non-invasive blood pressure monitoring. They will attend a physical examination, concerning Harris Hip Score for evaluation of hip movement, stability, strength, presence of any deformities, joint and functional limitations; radiographs of the axial pelvis and in anteroposterior, to determine the extent of the degree of arthritis or necrosis; pain assessment will be done using the model inside the Harris Hip Score, by adding evaluations of pain intensity (NRI scale) during orthostatic and clinostat posture.
During the surgery, a bone marrow sample will be collected. Bone marrow biopsy will be fixed for 24h in buffered 4% formalin and included in paraffin. 3µm sections will be used for bone marrow morphological and morphometric evaluation through hematoxylin/eosin staining protocol and for cellular immune-phenotypic typization.
Intervention type
Drug
Phase
Phase IV
Drug names
Tapentadol, NSAIDs/paracetamol
Primary outcome measure
1. Expression and functional characteristics of opioid receptors on the lymphocyte surface, measured using peripheral blood analysis (Immunophenotype analysis, Q-PCR, western blotting, ELISA) at T0, T2, T3, T4 and T5
2. Bone marrow morphological and morphometric evaluation, using bone marrow biopsy, hematoxylin/eosin staining protocol and cellular immune-phenotypic typization at T2
Secondary outcome measures
1. Hip movement, stability, strength, presence of any deformities, joint and functional limitations, evaluated using the Harris Hip Score at T0, T1, T2, T4, T5
2. Degree of arthritis/necrosis, measured using axial and anteroposterior pelvic radiographs at T0
3. Pain intensity, measured using the NRI scale at T0, T1,T2, T3, T4, T5
4. Electrocardiogram, oxygen saturation, invasive and non-invasive blood pressure monitoring at T2
5. Side effects evaluation (tolerance or addiction) at T2, T4, T5
Overall trial start date
23/05/2016
Overall trial end date
23/11/2017
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Patients who started opioid analgesics category and will undergo total hip arthroplasty for osteoarthritis or aseptic necrosis of the femoral head
2. Patients who started NonSteroidal Anti-Inflammatory Drugs (NSAIDs) and will undergo total hip arthroplasty (THA) for osteoarthritis or aseptic necrosis of the femoral head
3. Males and female adults (from 18 years old)
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
60 patients
Participant exclusion criteria
1. Unstable neurological pathologies
2. Uncompensated diabetes
3. Previous abdominal surgery with dynamic ileum risk
4. Viral infective pathologies
5. Patients unable to fill the informed consent form
6. Patients needing post-surgery mechanical ventilation
7. Patients attending a secondary surgery
8. Retreated patients
Recruitment start date
02/12/2016
Recruitment end date
02/08/2017
Locations
Countries of recruitment
Italy
Trial participating centre
ISAL Foundation
Via San Salvador 204
Torre Pedrera, Rimini
47922
Italy
Trial participating centre
Policlinico Tor Vergata
Viale Oxford, 81
Rome
00133
Italy
Sponsor information
Organisation
ISAL Foundation
Sponsor details
Via San Salvador 204
Torre Pedrera
47922
Italy
+39 (0)541 725166
amministrazione@fondazioneisal.it
Sponsor type
Research organisation
Website
Funders
Funder type
Research organisation
Funder name
ISAL Foundation
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
The trialists expect to publish the clinical and biological data in a high-impact peer reviewed journal.
IPD sharing statement
The datasets generated during and/or analysed during the current study will be stored in a non-publically available repository (IESSS - Ibis Enhanced Spontaneous Studies System).
Intention to publish date
23/11/2018
Participant level data
Stored in repository
Basic results (scientific)
Publication list
2017 protocol in: https://www.ncbi.nlm.nih.gov/pubmed/29258584