Clinical trial NCT01729195: Ankle Syndesmosis Fixation by Antibiotic Releasing Bioabsorbable Screw
Official title: An Antibiotic Releasing Bone Screw: a Randomized Clinical Trial of Patients With Weber C Type Ankle Fractures
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ankle Fracture
Keywords: bioabsorbable implant
bone screw
local antibiotic prophylaxis
syndesmosis injury
ankle fracture
ciprofloxacin
Lead sponsor: Turku University Hospital
Sponsor class: OTHER_GOV
Collaborators: name: Tampere University of Technology
First posted: 2012-11-20
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This single-center randomized trial evaluates the efficacy and safety of a new bone screw (antibiotic releasing bioabsorbable screw) in fixation of syndesmosis in patients with Weber C-type ankle fractures. The comparison is made to subjects treated by conventional metal screw fixation of the syndesmosis. The primary objective is to show that the antibiotic releasing bioabsorbable screw is at least as good as the routinely used metal screw in prevention of syndesmosis widening in patients with Weber C-type ankle fractures. The secondary objective is to show that the clinical outcome of the ankle fracture treatment is equal between patients treated by the antibiotic releasing bioabsorbable screw and the conventional metal screw.

Detailed description: This is a randomized parallel-group single centre study. All the patients enrolled will have an acute, closed Weber C-type ankle fracture. The ankle syndesmosis will be fixed using the new medical device (antibiotic containing bioabsorbable screw) or the routinely used device (metal screw). The investigational antibiotic containing bioabsorbable screw for ankle syndesmosis repair (the thread diameter 4.5 mm) will be made of bioabsorbable poly(lactide-co-glycolide) (PLGA) 80:20 and ciprofloxacin, which is a bactericidal antibiotic. The main purpose of the screw is to prevent syndesmosis widening after Weber C-type of ankle fracture. The secondary function of the screw is to reduce the risk for colonization of the implant with bacteria and subsequently prevent biomaterial-related infection. In the control group, a stainless steel screw will be used. All patients will receive the standard of care for concomitant fractures and other injuries of the ankle.

The key variables in the assessment will be radiostereometric (RSA) measurements of the syndesmosis width, CT imaging of the ankle mortise and standard radiographic evaluation of the syndesmosis width and ankle mortise. Clinical outcome of the ankle fracture treatment will be measured using standardized outcome questionnaires (RAND-36, AAOS Foot and Ankle Outcome Instrument, Olerud and Molander score, VAS pain scale). The follow-up of the patients will be 52 weeks. The metal screw will be removed 8 weeks after fracture surgery. The expected mechanical integrity of the bioabsorbable screw is 6 - 8 weeks, while the complete absorption time of the bioabsorbable screw in human body is expected to be approximately two years

Eligibility criteria: Inclusion Criteria:

* acute, closed Weber C-type ankle fracture
* adult patients (age 18-70 years)
* female subjects of child-bearing potential must have a negative pregnancy test and an approved contraception for the study duration

Exclusion Criteria:

* a previous fracture or infection of the injured ankle or the ipsilateral foot
* significant associated soft-tissue injury
* other long-bone fracture of the lower extremities
* documented active infection at any anatomic site
* a known metabolic skeletal disease (osteoporosis or osteomalasia) or a medication affecting bone structure (such as corticosteroid treatment)
* a pathological fracture
* any underlying systemic disease (such as unbalanced diabetes mellitus or rheumatoid disease) or a condition (such as alcoholism or drug abuse) which are known to affect resistance to infection
* history of prosthetic knee or hip replacement
* pregnant women or nursing mothers
* hypersensitivity to fluoroquinolones or related antibiotics (nalidixine acid)
* any other condition that in the judgment of the investigator would prohibit the subject from participating in the study or may hinder the collection of data and interpretation of the results

Primary outcomes:
measure: Radiostereometric analysis of the width of the syndesmosis
timeFrame: up to 12 weeks
Secondary outcomes:
measure: Computed tomography in evaluation of the restoration of the normal anatomy
timeFrame: Before surgery and repated at 0 and 12 weeks
Other outcomes:
measure: Conventional radiographic evaluation
timeFrame: Before surgery and at 0, 6, 12 and 52 weeks
measure: Systemic exposure to the released antibiotic
timeFrame: 6 weeks
measure: Functional recovery after ankle surgery
timeFrame: Before surgery and at 12 and 52 weeks
Locations:
city: Turku
country: Finland
facility: Turku University Hospital
Study officials:
affiliation: Turku University Hospital
name: Hannu T Aro, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Makinen TJ, Veiranto M, Knuuti J, Jalava J, Tormala P, Aro HT. Efficacy of bioabsorbable antibiotic containing bone screw in the prevention of biomaterial-related infection due to Staphylococcus aureus. Bone. 2005 Feb;36(2):292-9. doi: 10.1016/j.bone.2004.11.009.
citation: Makinen TJ, Mattila KT, Maattanen H, Aro HT. Comparison of digital and conventional radiostereometric image analysis in an ankle phantom model. Scand J Surg. 2005;94(3):233-8. doi: 10.1177/145749690509400311.
citation: Niemela SM, Ikaheimo I, Koskela M, Veiranto M, Suokas E, Tormala P, Waris T, Ashammakhi N, Syrjala H. Ciprofloxacin-releasing bioabsorbable polymer is superior to titanium in preventing Staphylococcus epidermidis attachment and biofilm formation in vitro. J Biomed Mater Res B Appl Biomater. 2006 Jan;76(1):8-14. doi: 10.1002/jbm.b.30414.
citation: Veiranto M, Tormala P, Suokas E. In vitro mechanical and drug release properties of bioabsorbable ciprofloxacin containing and neat self-reinforced P(L/DL)LA 70/30 fixation screws. J Mater Sci Mater Med. 2002 Dec;13(12):1259-63. doi: 10.1023/a:1021187331458.