Clinical trial NCT01016067: Tibial Delayed Healing Pivotal Clinical Trial
Official title: A Prospective, Randomized, Multicenter Pivotal Clinical Trial of the INFUSE/MASTERGRAFT™ Delayed Healing Device With Rigid Internal Fixation in the Treatment of Tibial Delayed Healing
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Tibial Delayed Healing
Keywords: Tibia
Tibial
Fracture
Nonunion
delayed
healing
iliac
crest
autograft
INFUSE
MASTERGRAFT
Fixation
Internal
Lead sponsor: Medtronic Spinal and Biologics
Sponsor class: INDUSTRY
First posted: 2009-11-18
Enrollment: 23
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Evaluate the INFUSE/MASTERGRAFT™ Delayed Healing Device as an alternative/replacement to autograft in the treatment of tibial delayed healing.

Detailed description: The purpose of this study is to evaluate the INFUSE/MASTERGRAFT™ Delayed Healing Device as an alternative/replacement to autograft in the treatment of tibial delayed healing. A subject will be considered to have tibial delayed healing when he/she is at least six months from the date of the most recent surgical intervention and has shown no signs of radiographic healing for at least three months. Radiographic signs of healing for this study are defined as either the progressive disappearance of fracture lines or the development of cortical continuity \[bridging bone\] at the site. All prospective patients must require surgical treatment with rigid internal fixation \[reamed IM nail or plate/screws\] and bone grafting.

Eligibility criteria: Inclusion Criteria:

1. Has tibial delayed healing. A subject will be considered to have delayed healing when he/she is at least six months from the date of the most recent surgical intervention and has shown no signs of radiographic healing for at least three months. (Radiographic signs of healing for this study are defined as either the progressive disappearance of fracture lines or the development of cortical continuity \[bridging bone\] at the site.)
2. Has delayed healing of the tibia that requires treatment with rigid internal fixation and bone grafting. (Stable rigid internal fixation hardware may already be in place prior to treatment. If required, the fixation hardware may be removed and replaced along with the placement of the bone graft.)
3. Has adequate soft tissue coverage at the delayed healing site. All prior soft tissue coverage procedures (e.g., skin grafts or flaps) should be sufficiently healed for placement of a bone graft prior to enrollment in the study.
4. Has a sufficient amount of iliac crest autograft available for a bone grafting procedure.
5. After walking 5 or 6 steps, has intensity of pain/discomfort at the injury site equal to or greater than 4 (as reported on the preoperative Delayed Healing Site Pain Questionnaire form; 0 being no pain and 10 being pain as bad as it could be).
6. Is at least 21 years of age and skeletally mature at the time of surgery.
7. If a female of child-bearing potential, patient is not pregnant or nursing and agrees not to become pregnant for one year following surgery in the study.
8. Is willing and able to comply with the study plan and able to understand and sign the Patient Informed Consent Form.

Exclusion Criteria:

1. Has a congenital pseudarthrosis or pathological fracture nonunion (not including osteoporosis-related fractures).
2. Has a tibial delayed healing with articular involvement (e.g., intra-articular). (The original fracture may have involved the joint, but the resulting delayed healing site may not involve the joint.)
3. Has hypertrophic tibial delayed healing (e.g., observed on x-ray as having an abundant callus or "horse hoof" appearance).
4. Has inadequate neurovascular status in the involved limb that may jeopardize healing.
5. Has an active or a known prior infection at the delayed healing site (e.g., the presence of purulent drainage from the site, prior positive cultures from the site, or evidence of active/prior osteomyelitis at the site). Enrolled subjects whose intra-operative cultures test positive for bacteria may remain in the study.
6. Has existing stable hardware that will not be removed and does not meet the algorithm requirements.
7. Has treatment planned for the delayed healing that does NOT include placement of a bone graft and/or rigid internal fixation consisting of a reamed intramedullary nail or plate/screws.
8. Has a tibial delayed healing injury site with a bony defect larger than 4 cm in length.
9. Has another injury/condition that prevents ambulation or completion of any of the study assessments.
10. Has a history of endocrine or metabolic disorder known to affect osteogenesis (e.g., Paget's disease, renal osteodystrophy, hyperthyroidism, parathyroid hormone disorder, Ehler-Danlos syndrome, osteogenesis imperfecta, calcium imbalance).
11. Has a Vitamin D deficiency, defined as a 25-hydroxy Vitamin D serum concentration of ≤11ng/mL .
12. Has an active malignancy or prior history of malignancy (except for basal cell carcinoma of the skin).
13. Has an overt or active systemic infection (e.g., HIV/AIDS, hepatitis, bacteremia).
14. Has been on oral or injectable steroids for six weeks or more at time of enrollment. This does not include episodic steroid use; inhaled steroids; or steroid medication (e.g., Epidural Steroid Injections, Medrol DosePaks) specifically for the perioperative management of symptoms.
15. Has a condition requiring postoperative medications that could interfere with bone healing of the implant, such as steroids. This does not include low dose aspirin for prophylactic anticoagulation; routine perioperative anti-inflammatory drugs; episodic steroid use; or inhaled steroids.
16. Has a history of certain autoimmune diseases. (Refer to the List of Autoimmune Diseases in the CIP for further information.)
17. Has a history of exposure to injectable collagen or silicone implants.
18. Has any previous exposure to any recombinant BMPs of either human or animal extraction.
19. Has a history of hypersensitivity to collagen or protein pharmaceuticals (e.g., monoclonal antibodies or gamma globulins).
20. Has a history of allergy to bovine collagen products.
21. Has a documented allergy or intolerance to metal or metal alloys, such as stainless steel or titanium.
22. Has chronic or acute renal and/or hepatic failure or prior history of renal and/or hepatic parenchymal disease.
23. Is mentally incompetent. If questionable, obtain psychiatric consult.
24. Is a prisoner.
25. Is an alcohol and/or drug abuser as defined by currently undergoing treatment for alcohol and/or drug abuse.
26. Has received treatment with an investigational therapy (drug, device, and/or biologic) within 28 days prior to implantation surgery or such treatment is planned during the 12-month period following the study surgery

Primary outcomes:
measure: Overall Success
timeFrame: 12 Months
Secondary outcomes:
measure: Radiographic Union Success
timeFrame: 12 months
measure: Success in Weight Bearing Ability
timeFrame: 12 months
measure: Success of Pain Status at the Delayed Healing Site
timeFrame: 12 months
measure: Success in Short Musculoskeletal Functional Assessment (SMFA)
timeFrame: 12 months
measure: Success in Short Form 36-Item (SF-36) Health Survey
timeFrame: 12 months
measure: Number of Subjects Having Additional Surgical Procedure Classified as a Treatment "Failure"
timeFrame: 12 months
Other outcomes:
Locations:
city: Denver
country: United States
facility: Denver Health
state: Colorado
city: Ft. Lauderdale
country: United States
facility: Shrock Orthopedic Research
state: Florida
city: Jacksonville
country: United States
facility: University of Florida College of Medicine
state: Florida
city: Orlando
country: United States
facility: Orlando Health
state: Florida
city: Fort Wayne
country: United States
facility: Fort Wayne Orthopaedics
state: Indiana
city: Indianapolis
country: United States
facility: Methodist Hospital
state: Indiana
city: Baltimore
country: United States
facility: Sinai Hospital of Baltimore
state: Maryland
city: Royal Oak
country: United States
facility: William Beaumont Hospital
state: Michigan
city: Columbia
country: United States
facility: University of Missouri
state: Missouri
city: St. Louis
country: United States
facility: St. Louis University Hospital
state: Missouri
city: Brooklyn
country: United States
facility: Lutheran Medical Center
state: New York
city: Charlotte
country: United States
facility: Carolinas Medical Center
state: North Carolina
city: Columbus
country: United States
facility: Ohio Health Research Center
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma
state: Oklahoma
city: Danville
country: United States
facility: Geisinger Clinic
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
Study officials:
References: