Condition category
Surgery
Date applied
13/05/2017
Date assigned
23/05/2017
Last edited
15/02/2018
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

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 measures

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

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

http://www.fondazioneisal.it/

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

Results - basic reporting

Publication summary

2017 protocol in: https://www.ncbi.nlm.nih.gov/pubmed/29258584

Publication citations

Additional files

Editorial Notes

15/02/2018: Publication reference added.