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| General |
| Study Status |
Completed |
Application Number /
Requirement Number |
P190009 / PAS001 |
| Date Original Protocol Accepted |
02/12/2021
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| Date Current Protocol Accepted |
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| Study Name |
TFAOS PAS
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| Device Name |
OPRA Implant System
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| Clinical Trial Number(s) |
NCT01725711
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| General Study Protocol Parameters |
| Study Design |
Prospective Cohort Study
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| Data Source |
Other Data Source
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| Comparison Group |
Objective Performance Criterion
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| Analysis Type |
Analytical
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| Study Population |
Adult: >21
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| Detailed Study Protocol Parameters |
| Study Objectives |
The Transfemoral Amputation Osseointegration Study (TFAOS) initiated on November 11, 2017 and is sponsored by the Henry Jackson Foundation. The sponsor of TFAOS has agreed to provide the data to Integrum, who will analyze the data consistent with FDA’s requested endpoints and then submit reports to the agency.
The TFAOS is a prospective, multicenter, cohort study to provide an ongoing assessment of the short-term (2 years) safety and effectiveness outcomes of the updated version of the OPRATM Implant system (e.g., improvements with components, AxorTM II, and instrumentation since the H080004 pivotal study).
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| Study Population |
Patients who have the OPRATM implant procedure performed at Walter Reed or Univeristy of California San Francisco (UCSF) and meet the eligibility criteria established in the study protocol.
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| Sample Size |
The sample size of 50 patients in the TFAOS study was calculated to power the primary endpoint in the study, i.e., the change in prosthetic use score. A sample size of 50 patients is also sufficient for the primary endpoints in the PAS analysis. With an alpha of 0.05, 50 subjects have >80% power to demonstrate that each primary endpoint result will be greater than 50%, assuming 70% success.
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| Key Study Endpoints |
Primary Endpoints
1. Rate of overall success at 2 years. The overall success is the composite primary safety and effectiveness endpoint.
a. Primary safety endpoint: Proportion of patients with no subsequent secondary surgical interventions and, at most, 2 superficial infections, at 2 years.
b. Primary effectiveness endpoint: Proportion of patients who achieve the minimally clinically important difference (MCID) for the total Q-TFA score (mean of all subscores, i.e., prosthetic use score, prosthetic mobility score, problem score, and global score) of 20.25 points, and radiographic success, defined as no radiographic loosening of the implant with a radiolucent zone wider than the thread depth surrounding the entire implant.
2. Proportion of patients who achieved either/or/none of primary safety endpoint or primary effectiveness endpoint at 2 years.
Secondary Endpoints
Proportion of patients who achieved the MCID for the Q-TFA prosthetic use score (19 points), prosthetic mobility score (11 points), problem score (-23 points), and global score (33 points), individually at 2 years after stage-2 surgery.
Change in each of total Q-TFA score, Q-TFA prosthetic use score, prosthetic mobility score, problem score and global score from baseline to 2 years after stage-2 surgery.
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| Follow-up Visits and Length of Follow-up |
2 years after Stage 2 Surgery
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| Interim or Final Data Summary |
| Actual Number of Patients Enrolled |
50, with 41 at Walter Reed and 9 at UCSF.
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| Actual Number of Sites Enrolled |
2
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| Patient Follow-up Rate |
The follow-up rates at 2 years were 90.2% (37/41) (Enrolled: 41, no deaths, 4 subjects withdrawn) for Walter Reed patients and 33.3% (3/9) (9 enrolled, 1
death, 1 lost to follow-up, 7 remaining subjects, for whom 3 have data) for UCSF patients.
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| Final Safety Findings |
The proportion of subjects with no subsequent secondary surgical interventions (SSI) and at most 2 superficial infections at 2 years was 65% (24/37) in
the Walter Reed cohort subjects and 77.8% (7/9) in the UCSF cohort subjects.
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| Final Effect Findings |
Effectiveness Results Walter Reed Cohort:
Primary Effectiveness Endpoint: The MCID >= 20.25 of the Q-TFA score and Radiological Success was met by 33/37 (89%) subjects, MCID >= 20.25 of the Q-TFA was met by 31/37 subjects (84%) and Radiologic success was met by 36/37 (97%) patients. (1 subject had implant loosening).
Secondary Effectiveness Endpoint: Proportion of subjects who achieved the MCID for the Q-TFA individually at 2 years after stage-2 surgery. It is noted between 76% and 95% of subjects (these percentages represent each of the four subsections of the Q-TFA) had an improvement at 2 years post OPRA implantation, meeting the MCID of the Q-TFA scores.
UCSF Cohort: Effectiveness data was obtained for three (3) of 9 enrolled subjects at the USCF at 2-year follow up , due to the limited data made available to Integrum by the study sponsor and the clinical site. 9. The effectiveness data is difficult to interpret and not conclusive, as there is a significant amount of missing data.
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| Study Strengths & Weaknesses |
Study Strengths and Weaknesses Strengths: The study was a prospective enrollment US cohort study with the intent to follow 50 patients for 2 years post-surgery.
The study utilized the Q-TFA (Questionnaire for Persons with a Transfemoral Amputation), which is a validated patient-reported outcome measure with established minimal clinically important differences (MCIDs) for assessing prosthetic function.
Weaknesses:
The study has substantial missing data from UCSF (6 of 9 enrolled subjects), reducing the analyzable population from 50 to 40 subjects. This represents a 20% data loss that compromises the study's statistical power and may introduce potential selection bias.
The study enrolled 50 transfemoral amputees across two US sites, representing a subset of the intended use population with appropriate demographics (86% male, 58% blast injuries) particularly for military personnel. The study results may not be generalizable to other US patients
Due to Integrum does not have access to per patient data or line data, the objective of using hypothesis testing to evaluate device performance using the composite endpoint comparing to a control (performance goal) could not be performed as required in the P190009 study protocol. Hence, the change to the PAS study design (from hypothesis testing to descriptive analysis) was the most appropriate way to evaluate the final results.
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| Recommendations for Labeling Changes |
Yes, a labeling change is recommended to update the device labeling with the final study results.
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