Adjunctive Therapy to Treat Tibial Shaft Fractures

Trauma Clinical Trial

— TSF  

Official title:

A Phase II Randomized, Controlled, Open-labeled (Dose-blinded) Dose Finding Study of the Safety and Efficacy of I-040202 in the Treatment of Patients With Acute Open Tibial Shaft Fractures

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00533793
• Other study ID #: CS I-040202/01
• Status: Completed
• Phase: Phase 2
• First received: September 20, 2007
• Last updated: March 15, 2012
• Start date: April 2007
• Est. completion date: May 2011

Study information

• Verified date: March 2012
• Source: Kuros Biosurgery AG
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A phase 2, prospective, randomized, controlled, open-label (dose-blinded), parallel group, international multi-center study. The study will consist of four treatment groups - one control group (SoC) and three I-040202 groups receiving SoC plus 0.133 mg/mL, 0.4 mg/mL or 1.0 mg/mL I-040202.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 201
• Est. completion date: May 2011
• Est. primary completion date: May 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Eligible patients must meet all of the following inclusion criteria:

1. patients with an acute open fracture of the tibial shaft secondary to trauma assessed by medical examination and current radiographs indicated for open fracture reduction and internal fixation using osteosynthesis plates or intra-medullary nails

2. soft tissue management (if medically warranted, eg. debridement, irrigation, application of antibiotics) performed according to local hospital practice no later than 24h after the trauma

3. male and female patients >= 18 years

4. body mass index (BMI) 16-33 (minimum body weight 50 kg, maximum 140 kg)

5. females of child-bearing potential must be willing to undergo a pregnancy test (urine) prior to treatment start (at screening)

6. females of child-bearing potential randomized in the intervention group must agree to have acceptable contraception for at least 3 months after receiving the study medication.

Acceptable contraceptive measures are:

• Hormonal types of birth control with a failure rate of less than 1% per year (such as implants, injections, combined oral contraceptives, patches or other methods) or copper IUDs or other IUDs with a failure rate of less than 1% per year, AND

• An additional barrier type of birth control measure (such as condoms, diaphragms, cervical caps, etc.) Sterilized women and abstinent women of child-bearing potential will not be required to take contraceptive measures

7. willingness and ability to understand, participate and comply with the study requirements

8. patient be able to give consent personally and sign the Informed Consent Form.

Exclusion criteria:

Patients will be not eligible if they meet one of the following exclusion criteria:

1. IIIc open fracture according to the Gustilo-Anderson classification

2. tibial defects requiring bone-grafting (e.g. large segmental defects)

3. duration from trauma to surgery longer than 14 days

4. concomitant acute bone injuries and/or major skin or other significant injuries that in the opinion of the investigator would interfere with the tibial shaft fracture healing process

5. concomitant ipsilateral tibial fractures other than in the diaphyseal region

6. evidence of immune suppression

7. suspected or known hypersensitivity to the study medication or components of it

8. evidence of hypercalcemia

9. hyperparathyroidism

10. on treatment and/or planned treatment with products containing PTH (e.g. Forteo)

11. pregnant or lactating females

12. participation in another clinical trial within the last 3 months

13. active or past history of malignant tumor

14. history or evidence for any hereditary or acquired chronic metabolic bone disease other than primary osteoporosis.

15. history or evidence for any clinically relevant organ failure or any other relevant medical condition that, in the opinion of the investigator, will relevantly interfere with the assessment of study outcome or will impose hazard to the patient if study therapy will be initiated

16. known history of allergy to anaesthetics

17. evidence of moderate or severe renal failure (serum creatinine > 3.0 times ULN, NCI CTC grades 3 and 4)

18. known history of allergic thrombocytopenia (type II) induced by heparin

19. inexplicable elevations of alkaline phosphatase or alkaline phosphatase > 5.0 times ULN, NCI CTC grades 3 and 4

20. prior external beam or implant radiation therapy to the skeleton

Related Conditions & MeSH terms

• Trauma

Intervention

Procedure:
• open fracture reduction
internal fracture fixation: osteosynthesis plates or intra-medullary nails

Locations

Country	Name	City	State
Bulgaria	MHAT ''Sveti Georgi'', Orthopaedic and Traumatology clinic (85)	Plovdiv
Bulgaria	MHATEM ''N.I.Pirogov'' Second clinic of Orthopaedic and Traumatology (84)	Sofia
Czech Republic	Czech Republic (51)	Brno
Czech Republic	Czech Republic (52)	Praha
Finland	Finland (71)	Kuopio
Finland	Finland (72)	Oulu
Finland	Finland (70)	Turku
France	France (14)	Dijon Cedex
France	France (16)	Dunkerque
France	France (15)	Limoges Cedex
France	France (11)	Rouen cedex
Germany	Germany (50)	Göttingen
Germany	Germany (43)	Kiel
Germany	Germany (40)	Leipzig
Germany	Germany (41)	Ludwigshafen
Germany	Germany (44)	München
Germany	Germany (42)	Ravensburg
Germany	Germany (45)	Rostock
Hungary	Fovarosi Onkormanyzat Szent janos Korhaza (81)	Budapest
Hungary	Hungary (54)	Debrecen
Hungary	Vaszary Kolos Hospital Esztergom (78)	Esztergom
Hungary	Hungary (79)	Kaposvar
Hungary	Hungary (55)	Nyiregyhaza
Hungary	Hungary (53)	Pecs
Italy	Italy (21)	Rozzano
Romania	Romania (58)	Bucharest
Romania	Romania (59)	Bucharest
Romania	Spitalul Universitar de Urgenta Bucuresti (87)	Bucharest
Romania	Romania (57)	Cluj Napoca
Romania	Spitalul Clinic Judetean Constanta (88)	Constanta
Romania	Romania (73)	Oradea
Romania	Romania (74)	Sibiu
Romania	Romania (56)	Timisoara
Serbia	Serbia (60)	Belgrade
Serbia	Serbia (61)	Belgrade
Serbia	Serbia (76)	Belgrade
Serbia	Serbia (62)	Kragujevac
Serbia	Serbia (75)	Novi Sad
Slovakia	Slovak Republic (65)	Banska Bysterica
Slovakia	Slovak Republic (64)	Bratislava 2
Slovakia	Slovak Republic (77)	Trnava
Slovakia	Slovak Republic (63)	Zilina
Slovenia	Slovenia (67)	Izola
Slovenia	Slovenia (66)	Novo mesto
Switzerland	Switzerland (02)	Aarau
Switzerland	Switzerland (03)	Davos
Switzerland	Switzerland (01)	Lausanne
Switzerland	Switzerland (04)	Luzern
Switzerland	Switzerland (05)	St. Gallen

Sponsors (2)

Lead Sponsor	Collaborator
Kuros Biosurgery AG	Baxter BioScience

Countries where clinical trial is conducted

Bulgaria,  Czech Republic,  Finland,  France,  Germany,  Hungary,  Italy,  Romania,  Serbia,  Slovakia,  Slovenia,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical Criteria:weight bearing,red.pain,walking without aid;lack of need for surg. interv. fracture site;Radiogr. crit.:Cortical bridging,disintegration/disappearance fracture lines,absence of signs for complications(infection,malunion)		short term follow-up: 6 months; long term follow-up: additional 6 months (total duration of 1 year)
Secondary	Prop. patients healed 3,9,12 mths after T0; prop. time, extent radiogr. union for 2,3,4,5,6,9,12 mths after T0; Eval.:6 and 12 mths; prop./invasiven. sec. interv. due to persistent non-union within 6,12 mths after T0.		short term follow-up: 6 months; long term follow-up: additional 6 months (1 year)