Tibial Delayed HealingPhase 3NCT01016067
Tibial Delayed Healing Pivotal Clinical Trial
A Phase 3 study testing INFUSE/MASTERGRAFT and Autograft bone in people with Tibial Delayed Healing, run by Medtronic Spinal and Biologics at 16 sites in United States.
Trial summary
Evaluate the INFUSE/MASTERGRAFT™ Delayed Healing Device as an alternative/replacement to autograft in the treatment of tibial delayed healing. Read more about this study
- Who is it for?
- Ages 21 years and olderHealthy volunteers can take part
- Conditions the study is for
- Tibial Delayed Healing
- What is being tested?
- INFUSE/MASTERGRAFT and Autograft bone
- Type of treatment
- Medical device, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 16 sitesUnited States
- Study dates
- Nov 2010to Dec 2013
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.)
- 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.)
- 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.
- Has a sufficient amount of iliac crest autograft available for a bone grafting procedure.
- 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).
- Is at least 21 years of age and skeletally mature at the time of surgery.
- 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.
- Is willing and able to comply with the study plan and able to understand and sign the Patient Informed Consent Form.
Who cannot join
- Has a congenital pseudarthrosis or pathological fracture nonunion (not including osteoporosis-related fractures).
- 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.)
- Has hypertrophic tibial delayed healing (e.g., observed on x-ray as having an abundant callus or "horse hoof" appearance).
- Has inadequate neurovascular status in the involved limb that may jeopardize healing.
- 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.
- Has existing stable hardware that will not be removed and does not meet the algorithm requirements.
Show all 26Show fewer
- 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.
- Has a tibial delayed healing injury site with a bony defect larger than 4 cm in length.
- Has another injury/condition that prevents ambulation or completion of any of the study assessments.
- 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).
- Has a Vitamin D deficiency, defined as a 25-hydroxy Vitamin D serum concentration of ≤11ng/mL .
- Has an active malignancy or prior history of malignancy (except for basal cell carcinoma of the skin).
- Has an overt or active systemic infection (e.g., HIV/AIDS, hepatitis, bacteremia).
- 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.
- 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.
- Has a history of certain autoimmune diseases. (Refer to the List of Autoimmune Diseases in the CIP for further information.)
- Has a history of exposure to injectable collagen or silicone implants.
- Has any previous exposure to any recombinant BMPs of either human or animal extraction.
- Has a history of hypersensitivity to collagen or protein pharmaceuticals (e.g., monoclonal antibodies or gamma globulins).
- Has a history of allergy to bovine collagen products.
- Has a documented allergy or intolerance to metal or metal alloys, such as stainless steel or titanium.
- Has chronic or acute renal and/or hepatic failure or prior history of renal and/or hepatic parenchymal disease.
- Is mentally incompetent. If questionable, obtain psychiatric consult.
- Is a prisoner.
- Is an alcohol and/or drug abuser as defined by currently undergoing treatment for alcohol and/or drug abuse.
- 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
Trial locations and contacts
16 sites in 1 country.
16 sites in 1 country
United States16 sites
Sinai Hospital of Baltimore
Baltimore, Maryland, 21215
Lutheran Medical Center
Brooklyn, New York, 11220
Carolinas Medical Center
Charlotte, North Carolina, 28204
University of Missouri
Columbia, Missouri, 65201
Ohio Health Research Center
Columbus, Ohio, 43215
Geisinger Clinic
Danville, Pennsylvania, 17822
Denver Health
Denver, Colorado, 80204
Shrock Orthopedic Research
Fort Lauderdale, Florida, 33316
Fort Wayne Orthopaedics
Fort Wayne, Indiana, 46804
Methodist Hospital
Indianapolis, Indiana, 46202
University of Florida College of Medicine
Jacksonville, Florida, 32209
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
University of Oklahoma
Oklahoma City, Oklahoma, 73104
Orlando Health
Orlando, Florida, 32806
William Beaumont Hospital
Royal Oak, Michigan, 48073
St. Louis University Hospital
St Louis, Missouri, 63104
About this study
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
Evaluate the INFUSE/MASTERGRAFT™ Delayed Healing Device as an alternative/replacement to autograft in the treatment of tibial delayed healing.
Read the 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.
- Conditions
- Tibial Delayed Healing
- Being tested
- INFUSE/MASTERGRAFT, Autograft bone
- Keywords
- Tibia, Tibial, Fracture, Nonunion, delayed, healing, iliac, crest, autograft, INFUSE, MASTERGRAFT, Fixation, Internal
- Medical subject headings
- Fractures, Bone, Scleroderma, Limited
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
INFUSE/MASTERGRAFTDevice
Also called INFUSE, MASTERGRAFT
INFUSE® (rhBMP-2) on an absorbable collagen sponge (ACS) and MASTERGRAFT® granules with appropriate rigid internal fixation hardware (reamed IM nail or plate/screws)
Autograft boneProcedure or surgery
Also called Autogenous bone graft
Autogenous bone graft with appropriate rigid internal fixation hardware (reamed IM nail or plate/screws)
| Study group | Role | What they receive |
|---|---|---|
| INFUSE/MASTERGRAFT | Experimental | Patients received INFUSE/MASTERGRAFT granules with rigid internal fixation. Receives: Device: INFUSE/MASTERGRAFT |
| Autograft bone | Active comparator | Patients received autograft bone with rigid internal fixation. Receives: Procedure: Autograft bone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Success
Overall success is reported as participants who met all of the following criteria: 1. radiographic union success; 2. success in weight bearing ability; 3. improvement in pain at the delayed healing site; 4. no serious adverse event classified as "implant-associated" or "implant/surgical procedure-associated" (device-related); 5.no additional surgical procedures classified as a failure.
Measured: 12 Months
Secondary outcomes (6)
Radiographic Union Success
Radiographic union success (a component of overall success) was defined as complete disappearance of fracture lines or the presence of bridging bone across the delayed healing site as observed on at least three of the four cortices (anterior, posterior, medial, and lateral), using plain films. If there was more than one delayed healing fracture line, all fracture lines must have been united in order to be considered a successful fracture union.
Measured: 12 months
Success in Weight Bearing Ability
Success in weight bearing ability (a component of overall success) was defined that subject was able to bear weight without severe pain on the affected limb. The subject was asked to stand, bearing full weight on the affected limb in a single-leg stance without ambulatory assistance for 10 seconds. If the subject was able to do so without severe pain, a positive (success) response was recorded. If the subject was either unable to stand on the affected limb in a single-leg stance or declined to do so because of limb weakness, poor balance, or severe leg pain, a negative (failure) response was documented.
Measured: 12 months
Success of Pain Status at the Delayed Healing Site
After walking five or six steps, subjects rated their intensity of pain/discomfort at the delayed healing site using a numerical rating scale from 0-10, with a score of 0 representing "no pain" and a score of 10 representing "pain as bad as it could be". Subjects who were unable or declined to walk because of severe leg pain were considered to have a score of 10. Success for pain at the delayed healing site was defined as at least a 2-point improvement in pain from the pre-operative score. Success of pain status at the delayed healing site was a component of overall success.
Measured: 12 months
Success in Short Musculoskeletal Functional Assessment (SMFA)
The SMFA is an assessment tool that measures a subject's overall function for a broad range of musculoskeletal injuries and disorders. The SMFA results were summarized into two components, the dysfunctional index and the bother index. Success for the SMFA assessment was defined as any improvement post-operatively as compared to the pre-operative condition.
Measured: 12 months
Success in Short Form 36-Item (SF-36) Health Survey
SF-36 was used to assess general health status. The SF-36 results were summarized into two components, a physical component summary (PCS) and a mental component summary (MCS). Success was defined as any improvement in a subject's SF-36 PCS post-operatively as compared to the pre-operative condition.
Measured: 12 months
Number of Subjects Having Additional Surgical Procedure Classified as a Treatment "Failure"
Subject who had a surgery after the original study treatment was classified as a treatment "failure" if the additional surgery or treatment occurred in the involved limb and affected the study treatment and/or its mechanism of action in relation to the diagnosis or condition of the subject that was the cause for having the original study treatment.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Nov 2009 (estimated)
- Study startNov 2010
- Primary completionOct 2013
- Study completionDec 2013
Why it stopped: Difficulty in patient recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Tibial Delayed HealingStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medtronic Spinal and Biologics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01016067
- Sponsor's protocol ID
- Medtronic P07-01
- Status last verified
- Jan 2015
- First submitted
- 17 Nov 2009
- Last updated
- 21 Jan 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 21 Jan 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01016067
- Acronym / sponsor ID
- Medtronic P07-01
- Conditions
- Tibial Delayed Healing
- Keywords
- Tibia, Tibial, Fracture, Nonunion, delayed, healing, iliac, crest
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Difficulty in patient recruitment
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Medtronic Spinal and BiologicsIndustry (pharma, biotech, devices)
- Study start
- Nov 2010
- Primary completion
- Oct 2013 (actual)
- Study completion
- Dec 2013 (actual)
- First posted
- 18 Nov 2009 (estimated)
- Results
- Posted 4 Nov 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| INFUSE/MASTERGRAFT | Experimental | Device: INFUSE/MASTERGRAFTPatients received INFUSE/MASTERGRAFT granules with rigid internal fixation. |
| Autograft bone | Active comparator | Procedure: Autograft bonePatients received autograft bone with rigid internal fixation. |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.)
- 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.)
- 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.
- Has a sufficient amount of iliac crest autograft available for a bone grafting procedure.
- 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).
Key exclusion criteria (26 listed)
- Has a congenital pseudarthrosis or pathological fracture nonunion (not including osteoporosis-related fractures).
- 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.)
- Has hypertrophic tibial delayed healing (e.g., observed on x-ray as having an abundant callus or "horse hoof" appearance).
- Has inadequate neurovascular status in the involved limb that may jeopardize healing.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| INFUSE/MASTERGRAFTAlso: INFUSE, MASTERGRAFTINFUSE® (rhBMP-2) on an absorbable collagen sponge (ACS) and MASTERGRAFT® granules with appropriate rigid internal fixation hardware (reamed IM nail or plate/screws) | Device | INFUSE/MASTERGRAFT |
| Autograft boneAlso: Autogenous bone graftAutogenous bone graft with appropriate rigid internal fixation hardware (reamed IM nail or plate/screws) | Procedure or surgery | Autograft bone |
Primary outcome
Overall Success
Time frame: 12 Months
Overall success is reported as participants who met all of the following criteria: 1. radiographic union success; 2. success in weight bearing ability; 3. improvement in pain at the delayed healing site; 4. no serious adverse event classified as "implant-associated" or "implant/surgical procedure-associated" (device-related); 5.no additional surgical procedures classified as a failure.
6 secondary outcomes
Radiographic Union Success
Time frame: 12 months
Success in Weight Bearing Ability
Time frame: 12 months
Success of Pain Status at the Delayed Healing Site
Time frame: 12 months
Success in Short Musculoskeletal Functional Assessment (SMFA)
Time frame: 12 months
Success in Short Form 36-Item (SF-36) Health Survey
Time frame: 12 months
Number of Subjects Having Additional Surgical Procedure Classified as a Treatment "Failure"
Time frame: 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jan 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Tibial Delayed Healing
RecruitingObservational study
Prospective Validation Study of the CD8+TEMRA Cells As a Prognostic Biomarker of Healing Outcome After Fracture
Fracture Non Union, Fracture Healing
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
16 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing INFUSE/MASTERGRAFT and Autograft bone in people with Tibial Delayed Healing, run by Medtronic Spinal and Biologics at 16 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 21 Jan 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Nov 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Success (time frame: 12 Months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jan 2015; AzTrials last refreshed its copy on 6 Nov 2026.