Condition category
Musculoskeletal Diseases
Date applied
07/02/2018
Date assigned
08/02/2018
Last edited
02/07/2018
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Arthrofibrosis is one of the most common complications after knee replacement surgery and occurs in up to 16% of patients. It is defined as painful limitation in knee range of motion. An extended scar tissue layer cause by chronic inflammation can be observed within the joint. An accumulation of free radicals may lead to this excessive tissue formation. Vitamin C is a reducing agent that eliminates free radicals. The aim of this study is to find out whether vitamin C supplementation can prevent arthrofibrosis after knee replacement.

Who can participate?
Patients aged 18 and over with advanced osteoarthritis of the knee undergoing knee replacement surgery

What does the study involve?
Participants are randomly allocated to take either vitamin C to a placebo (dummy) supplement every day starting on the day before their operation and continuing for a total of 50 days. Knee joint range of motion is measured before the operation and at 8 weeks and 12 months after the operation.

What are the possible benefits and risks of participating?
If the study shows that vitamin C improves range of motion, it could provide valuable information about a possible new treatment. Prolonged courses of painful rehabilitation or even further surgery could be avoided. By reducing the need for further treatment and hospital stay healthcare costs could be lowered. Besides the risks of vitamin C overdose which are well documented and described in the product information, no further risks are expected.

Where is the study run from?
Cantonal Hospital St Gallen (Switzerland)

When is the study starting and how long is it expected to run for?
February 2010 to July 2016

Who is funding the study?
Cantonal Hospital St Gallen (Switzerland)

Who is the main contact?
Dr Henrik Behrend

Trial website

Contact information

Type

Public

Primary contact

Dr Henrik Behrend

ORCID ID

Contact details

Cantonal Hospital St Gallen
Rorschacherstreet 95
St Gallen
9007
Switzerland

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

CTU 10/050

Study information

Scientific title

Perioperative Vitamin C supplementation following total knee arthroplasty: a double-blind placebo-controlled randomized study

Acronym

Study hypothesis

Arthrofibrosis (AF) is a debilitating complication after total knee arthroplasty (TKA) with a reported incidence of up to 16%. It is considered a clinical diagnosis defined as limited range of motion (ROM) in flexion and/or extension as a result of post-operative soft-tissue fibrosis.

The primary objective of the study is to investigate whether the administration of vitamin C improves the range of motion (ROM) in patients undergoing TKA. It is hypothesized that vitamin C improves the joint mobility, avoids intra articular tissue damages by eliminating free radicals and reduces thereby the risk for arthrofibrosis in patients undergoing TKA.

Ethics approval

Ethics Committee of the Cantonal Hospital St Gallen, 27/10/2010, ref: EKSG 10/098

Study design

Single-center randomized double-blind placebo-controlled two-arm Phase IV study

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Prevention

Patient information sheet

Not available in web format, please use contact details to request a participant information sheet

Condition

Arthrofibrosis

Intervention

Registered patients were randomized to either VC at a daily dose of 1000 mg (two 500 mg tablets) or to matching placebo starting on the preoperative day and continuing for a total of 50 days. Randomization of patients was performed by the Clinical Trials Unit (CTU) using R statistical software version 2.9.2. VC and matching placebo was kindly provided by Burgerstein/Antistress AG (Rapperswil-Jona, Switzerland). Treatment compliance was assessed using a drug diary at 8 weeks (± 2 weeks) postoperatively.

Intervention type

Supplement

Phase

Drug names

Primary outcome measure

Knee joint ROM measured with a goniometer by a trained study nurse who was blinded to the research history, assessed preoperatively, at 8 weeks and 12 months postoperatively

Secondary outcome measures

1. Incidence of arthrofibrosis (AF), defined as extension deficit >5° and/or ≤ 100° flexion of the knee, measured at 8 weeks and 12 months postoperatively
2. Vitamin C plasma concentrations measured in µmol/l before surgery and 4 and 7 days after surgery
3. The Western Ontario and McMaster Universities Arthritis Index (WOMAC) measured at 8 weeks and 12 months postoperatively
4. The Forgotten Joint Score-12 (FJS-12) measured at 8 weeks and 12 months postoperatively

Overall trial start date

10/02/2010

Overall trial end date

12/07/2016

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Patients with primary osteoarthritis of knee joint undergoing TKA presenting with grade 3 or 4 osteoarthritis (Kellgren-Lawrence score)
2. Age ≥18 years
3. Written informed consent, including written consent to participate in the local prosthesis registry of the hospital

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

With a two-sided significance level of 5%, and a total of 240 patients (including a dropout rate of 20%), the study had a power of 80% to detect a mean difference of 5 degrees in ROM at 8 weeks and 12 months postoperatively.

Participant exclusion criteria

1. History of nephrolitiasis, hematochromatosis, uremia, beta-thalassemia
2. Known intolerance to vitamin C or any of the excipients
3. Dietary vitamin C intake <3 days before intervention
4. CRP values >10mg/l

Recruitment start date

01/07/2011

Recruitment end date

01/04/2015

Locations

Countries of recruitment

Switzerland

Trial participating centre

Kantonsspital St Gallen
Rorschacherstreet 95
St Gallen
9007
Switzerland

Sponsor information

Organisation

Cantonal Hospital St Gallen

Sponsor details

Rorschacherstreet 95
St Gallen
9007
Switzerland

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Hospital/treatment centre

Funder name

Cantonal Hospital St Gallen

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

The trialists are planning to publish a manuscript with the title: "Perioperative Vitamin C Supplementation following Total Knee Arthroplasty: A double-blind placebo-controlled randomized study" in an orthopaedic Journal in March 2018.

IPD sharing statement
The datasets generated during and/or analysed during the current study are not expected to be made available as consent was not obtained from the participants.

Intention to publish date

10/03/2018

Participant level data

Not expected to be available

Basic results (scientific)

Publication list

2018 results in: https://www.ncbi.nlm.nih.gov/pubmed/29955932

Publication citations

Additional files

Editorial Notes

02/07/2018: Publication reference added.