Chronic Pain, Inflammation and Infection After Joint Replacement

Extended Biochemical Analysis and Bacteriologic Diagnosis in Patients With Loose Joint Replacements, Chronic Pain and Infection.

Revision surgery after total hip or knee arthroplasty is an ongoing issue due to an increasing number of primary surgeries. Patients seek physicians due to pain. The cause is divided between loosening, infection or chronic pain. Some are operated on the suspicion of a chronic infection. However, postoperative microbiological testing does not always correlate with the suspicion and the operation may have been superfluous.

The objective is to employ a highly advanced diagnostic algorithm based on state of the art diagnostic techniques in order to improve the basis of preoperative diagnosis. Through this approach treatment can be given according to the causal problem.

Study Overview

• Status: Completed
• Conditions: Joint Prosthesis; Infection and Inflammatory Reaction
• Intervention / Treatment: Biological: Blood samples

Detailed Description

The aim of the project is to improve the preoperative diagnosis of infections and persistent pain in patients with prosthesis-related problems. Prosthesis infection is of chronic nature. Recent research has shown that one important explanation of this is the formation of encapsulated 'bacterial communities' on the surface of the prosthesis, where bacteria are well protected against antibiotic treatment. Surgery is therefore necessary for this patient group. But it is important to make diagnosis more accurate than it currently is today. In contrast, patients with persistent pain, but no indication of infection or prosthetic loosening, are best served by avoiding surgery, and instead receiving a treatment that is directed against the chronic pain condition. Based on the pain research carried out at Aalborg University, an understanding of chronic pain and treatment principles that would be beneficial for this patient group have been developed.

The investigators want to:

1. describe the postoperative course of specific serologic markers for primary and secondary total hip arthroplasty (THA) and total knee arthroplasty (TKA).
2. describe the bacteriologic diversity through revision of THA and TKA using cultivation techniques and molecular biological analysis comprehensive fluorescence in-situ hybridization (FISH), cloning and phylogeny, quantitative polymerase chain reaction (qPCR) and gene expression profiling.
3. describe pain and sensitization with new diagnostic technology in patients with stem loosening, suffering from infection and pain.
4. apply to a new diagnostic algorithm for the diagnosis of infection and pain following THA and TKA, which includes pain assessment, diagnostic X-ray, bone scintigraphy, PET scan, percutaneous biopsy, specific serologic parameters and molecular biological analysis.
5. describe the effect of the diagnostic algorithm, compared with a descriptive retrospective cohort of patients who have undergone revision of THA or TKA.

• Study Type: Observational
• Enrollment (Actual): 180

Contacts and Locations

Study Locations

• Denmark
  • Aalborg, Denmark, 9000
    • Northern Orthopaedic Division, Aalborg University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Primary care clinic.

Description

Inclusion Criteria:

• Patients undergoing primary uncemented total hip-joint replacement surgery
• Patients undergoing primary hybrid total hip-joint replacement surgery
• Patients undergoing total knee-joint replacement surgery

Exclusion Criteria:

• Patients younger than 18 years old
• Unability to speak or read Danish
• Pregnancy or lactating
• Bilateral disease
• Cancer
• Inability to give informed consent

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
40 patients (uTHA); Patients undergoing primary uncemented total hip arthroplasty surgery.	Biological: Blood samples; 4 x 10 ml blood samples.
40 patients (hTHA); 40 patients undergoing primary hybrid total hip replacement surgery.	Biological: Blood samples; 4 x 10 ml blood samples.
40 patients (TKA); 40 patients undergoing total knee replacement surgery.	Biological: Blood samples; 4 x 10 ml blood samples.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Examination of blood test parameters	The outcome measure is a composite. In order to predict the risk of developing a serious infection we want to: develop serum concentration markers; describe bacteriological diversity; perform qualitative assessment of pain and sensitization	4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Collect systematic data	The outcome measure is a composite. We want to collect systematic collect systematic data with a view to identify which specific blood parameters can best predict the risk that the patient develops a serious infection. Furthermore, we want to collect systematic data with a view to optimize the diagnostic algorithm.	4 years
Generate a knowledge base	The outcome measure is a composite. We want to generate a knowledge base for optimal antibiotic treatment, optimal pain management, optimal treatment of infection and pain caused by THA and TKA.	4 years

Collaborators and Investigators

• Sponsor: Northern Orthopaedic Division, Denmark
• Collaborators: University of Aarhus; The Ministry of Science, Technology and Innovation, Denmark
• Investigators: Principal Investigator: Sten Rasmussen, M.D., Northern Orthopaedic Division, Aalborg University Hospital

Study record dates

Study Major Dates

• Study Start: January 1, 2010
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: June 24, 2014
• First Submitted That Met QC Criteria: June 26, 2014
• First Posted (Estimate): June 27, 2014

Study Record Updates

• Last Update Posted (Estimate): April 10, 2015
• Last Update Submitted That Met QC Criteria: April 9, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: Inflammation; Infection; Pain; Prosthesis
• Additional Relevant MeSH Terms: Pathologic Processes; Pain; Neurologic Manifestations; Disease Attributes; Inflammation; Infections; Communicable Diseases; Chronic Pain
• Other Study ID Numbers: N-20110022