Locally Administered Clodronate in the Prevention of Aseptic Implant Loosening

NCT03803839 | Completed Early Phase 1

• 1 other identifier: Ei tiedossa
• Study Type: interventional
• Target: 19
• Locations: 0 countries
• Sites: N/A

Brief Summary

Periprosthetic bone-loss after total hip arthroplasty (THA), detected as an early migration of the prosthesis, may predict later loosening. The investigators hypothesized that by reducing bone resorption after THA with bisphosphonates, it might be possible to achieve better early fixation of the implant. Nineteen patients suffering arthrosis were recruited to a prospective, double-blinded, randomized, placebo-controlled clinical pilot trial. Patients were operated with an uncemented Bimetric stem with tantalum markers, the acetabular cup and liner were chosen by the surgeon. The femoral proximal intramedullary canal was rinsed with 1mM (millimole) clodronate, that was done by adding the clodronate to the 1000 ml 0.9% NaCl (sodium chloride) in nine patients and rinsing solution was the pure 0.9% NaCl for 10 patients. These rinsing packages were labeled only with the code from the pharmacy of the hospital. These patients were followed for two years using radiostereometric analysis (RSA), dual energy x-ray absorptiometry (DXA) and the Harris hip score (HHS). The purpose of the investigator's study was to examine whether the local intraoperative administration of clodronate could reduce periprosthetic bone loss and further stem migration after primary THA.

Conditions

Hip Arthrosis

Keywords

RSA; DXA; Bisphosphonates; Migration of stem; Aseptic loosening of prosthesis

Outcome Measures

Primary Outcomes (1)

• Maximal total point motion (MTPM) - migration of the femoral stem

  It represents the length of the translation vector of the point in a rigid body that has the greatest motion. It can only have positive values, and is not normally distributed. The reason for using MTPM is that in many cases, motion implies a biological effect of some kind and this effect is liable to be greatest at the point of maximum motion. The parameter has been measured by RSA-methods, which is an accurate method of determining the migration and wear of orthopaedic implants: it determine the precise location of two distinct objects relative to each other in three dimension such as the relative position of the femoral component and the proximal femur. In radiostereometric analysis the position in space of the original object is reconstructed from a two dimensional x-ray film using tantalum beads. Movement between segments is then calculated by localizing each segment in a coordinate system. Lower values represent a better outcome.

  0 to 24 months

Secondary Outcomes (1)

• Bone mineral density (BMD) in 7 Gruen zones

  0 to 24 months

Other Outcomes (4)

• Migration of femoral stem

  0 to 24 months

• The maximal (MTPM) maximal total point motion

  3 to 24 months

• Correlation between baseline BMD and the maximal MTPM

  BMD (0 month) - the maximal MTPM 3 to 24 months

Study Arms (2)

Clodronate

ACTIVE COMPARATOR

1 mM clodronate (60 mg in 1000 ml saline) was used intraoperatively during total hip arthroplasty: before installation of the prosthesis, the rinsing was performed with pulsatile lavage using the clodronate solution. The time for rinsing was about one minute.

Drug: Clodronate

Saline

PLACEBO COMPARATOR

1000 ml saline was used intraoperatively during total hip arthroplasty: before installation of the prosthesis, the rinsing was performed with pulsatile lavage using the saline solution. The time for rinsing was about one minute.

Drug: Saline

Interventions

Clodronate DRUG

Clodronate

Saline DRUG

Saline

Eligibility Criteria

• Age: Up to 73 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• hip arthrosis and
• a primary THA was planned

You may not qualify if:

• renal insufficiency
• hypercalcemia
• malignant tumors
• contemporaneously treatment with another bisphosphonate or aminoglycoside

Sponsors & Collaborators

• University of Oulu: lead

MeSH Terms

Conditions

Osteoarthritis, Hip

Interventions

Clodronic Acid; Sodium Chloride

Condition Hierarchy (Ancestors)

Osteoarthritis; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Intervention Hierarchy (Ancestors)

Diphosphonates; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Patients were randomized into two treatment groups; either the clodronate or a placebo group. All patients, surgeons and other personnel in the operating theatre were blinded as to the patients' study group.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: In this prospective, double-blinded, randomized, placebo-controlled clinical trial with two years follow-up period the investigators rinsed the proximal intramedullary cavity of the femur with either clodronate (60 mg clodronate in 1000 ml saline) or saline (1000 ml saline) prior to the application of the femoral stem.

Study Record Dates

• First Submitted: January 4, 2019
• First Posted: January 15, 2019
• Study Start: March 26, 2004
• Primary Completion: March 12, 2014
• Study Completion: March 12, 2014
• Last Updated: January 18, 2019

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Data will be available after submitting the results to the scientific journals and five years after the publication.
• Access Criteria: Data Access requests will be reviewed By an external Independent Review Panel. Requestors will be required to sign a Data Access Agreement.