(274 days)
DuraGraft Vascular Conduit Solution is a solution indicated for adult patients undergoing Coronary Artery Bypass Grafting Surgeries and is intended for flushing and storage of the saphenous vein grafts from harvesting through grafting for up to 4 hours.
DuraGraft Vascular Conduit Solution is a clear, colorless to slightly yellow, aseptically processed, non-pyrogenic solution for room temperature flushing and storage of vascular conduits used during the harvesting and grafting interval in Coronary Artery Bypass Grafting (CABG) surgeries. DuraGraft Vascular Conduit Solution is supplied in two separate containers composed of a Solution A (237.5mL) and a Solution B (12.5-13.5mL). Solution A is mixed with 12.5mL of Solution B prior to use. DURAGRAFT Vascular Conduit Solution has an osmolality of about 305 mOsmol/kg, viscosity of 1.06 cST, a sodium concentration of 155-160 mEq/L, a potassium concentration of 5.8 mEq/L, and a pH of about 7.4 at room temperature.
The provided document describes the DuraGraft Vascular Conduit Solution, a medical device used for flushing and short-term storage of saphenous vein grafts during Coronary Artery Bypass Grafting (CABG) surgeries.
The acceptance criteria for the device are implicitly defined by the "Risks to Health" and "Special Controls" sections, which outline the potential risks associated with such devices and the measures necessary to mitigate them, along with specific performance characteristics that must be demonstrated.
Here's an analysis of the acceptance criteria and the studies proving the device meets them:
1. Table of Acceptance Criteria and Reported Device Performance
| Acceptance Criteria (Derived from Risks to Health & Special Controls) | Reported Device Performance |
|---|---|
| 1. Adverse Tissue Reaction | Biocompatibility Evaluation: |
- Device evaluated per ISO 10993-1. Testing on final mixed solution and heparin mixture included Cytotoxicity, Irritation, Guinea Pig Maximization Test (GPMT) sensitization, Acute systemic toxicity, Hemolysis, Material mediated pyrogen, and Chemical leachable testing.
- Results "supported the biocompatibility of the DuraGraft device." |
| 2. Damage to Vascular Grafts (leading to MACE or Vascular Injury) | a) Clinical Performance Data (DuraGraft Prospective Randomized Study):- Safety Endpoints: Vein graft occlusions: 7.2% for DuraGraft vs. 8.8% for saline. Fitzgibbon class B/O stenosis: 1.6% for DuraGraft vs. 2.4% for saline. MACE: 0 for DuraGraft vs. 1 (0.8%) for saline. Composite event rate: 8.8% for DuraGraft vs. 11.2% for saline.
- Anatomic Parameters: At 12 months, DuraGraft treated SVGs had smaller mean wall thickness (0.12±0.06 mm vs. 0.20±0.31 mm for saline) and change in maximal focal narrowing (0.2 ± 3.8 mm vs. 4.7 ± 12.7 mm for saline).
b) Non-clinical Performance Testing: - Maintenance of Cell Viability & Structural Integrity:
- Pachuk et al., 2019: Maintained graft cell viability in human saphenous vein segments for up to 5 hours. Showed normal morphology and strong immunostaining of endothelial surface markers (CD31 and vWF) at both 45 minutes and 24 hours (NSS showed loss of viability at 15 minutes, multifocal aggregation/missing patches of endothelium at 24 hours, weaker CD31/vWF staining).
- Aschacher et al., 2021: Showed normal endothelial and sub-endothelial structure in DuraGraft-treated grafts (RL-treated showed damaged endothelial surface and beginning incongruence of intimal structure). Associated with lower reactive oxygen species and significant increase in oxidation-reduction potential.
- Korkmaz-Icoz et al., 2021: Alleviated vasoactive physiologic arterial dysfunction in rat aortic rings compared to saline. c) Shelf life testing:
- Testing supported a 3-year shelf life. |
| 3. Particulate Matter Contamination | a) Non-clinical Performance Testing (Bench Testing):
- Evaluation of visible and non-visible particulates in the final mixed solution (per USP ).
b) Shelf life testing: - Conducted after aging and simulated shipping, including container closure integrity (CCI) testing. |
| 4. Infection | Sterilization Validation: - Aseptically processed. Sterilization testing validated sterility of containers with SAL of 10-6. Endotoxin testing used 3-log reduction as acceptable level. Aseptic filling in accordance with EN ISO 13408-2:2011 and FDA guidance. Testing included aseptic filling validation and filter validation. Sterility and endotoxin testing provided following aging. |
| 5. Stability of Device's Chemical Components | Shelf Life Testing: - Testing conducted to evaluate the stability of Solution B (arginine, glucose, ascorbic acid, and glutathione) at time points from 0 to 36 months to support device stability and a 3-year shelf-life. Evaluation of pH (USP ) and osmolality (USP ). |
| 6. Labeling Requirements | Labeling Provided: - Instructions for use and package labels provided. Includes intended patient population, maximum storage duration (up to 4 hours), L-arginine component warning, not for direct injection/IV infusion, pre-use inspection of containers, re-use hazard warning, summary of non-clinical and clinical performance testing. |
2. Sample Size Used for the Test Set and Data Provenance
DuraGraft Prospective Randomized Study:
- Sample Size: 125 patients were randomized.
- 125 grafts treated with DuraGraft.
- 125 grafts treated with Saline (control).
- Data Provenance:
- Country of Origin: Canada, Ireland, and Denmark.
- Retrospective or Prospective: Prospective, multicenter, randomized controlled trial.
DuraGraft EU Registry:
- Sample Size: 2,964 patients enrolled.
- 4,454 venous grafts and 586 arterial conduits treated with DuraGraft.
- Data Provenance:
- Country of Origin: Austria, Germany, Ireland, Italy, Spain, Switzerland, Turkey, and United Kingdom.
- Retrospective or Prospective: Ongoing European post-market study (Observational Registry) designed to support an international CABG registry database.
Propensity Matched Comparison of DuraGraft EU Registry to STS Registry:
- Sample Size: 2,400 patients were matched from the DuraGraft cohort to 2,400 patients in the STS Database.
- Data Provenance:
- Country of Origin: DuraGraft (Europe) vs. STS (US and US territories for mortality data linkage).
- Retrospective or Prospective: Retrospective comparison analysis using existing registry data.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
The document does not explicitly state the number of experts or their specific qualifications used to establish ground truth for the clinical test sets in the DuraGraft Prospective Randomized Study or the DuraGraft EU Registry.
However, the "DuraGraft Prospective Randomized Study" mentions "adjudicated safety outcomes" and "MDCT analysis." In clinical trials, adjudication typically involves a committee of independent clinical experts, but their number and specific qualifications (e.g., "radiologist with 10 years of experience") are not detailed here. Similarly, MDCT analysis would be interpreted by trained radiologists or cardiologists, but their specific experience levels are not provided.
For the "Propensity Matched Comparison," the ground truth for mortality was established via linkage to the US National Death Index (NDI), which is a governmental database of all death records. This does not involve individual expert review for each case.
4. Adjudication Method for the Test Set
- DuraGraft Prospective Randomized Study: The document states "Adjudicated safety outcomes" in the table. This implies an adjudication process was used, likely by an independent committee, but the specific method (e.g., 2+1, 3+1) is not detailed.
- DuraGraft EU Registry: No specific mention of an adjudication method is provided for the registry data. Outcomes like MACE and individual components are reported, which are typically derived from clinical records and may or may not undergo independent adjudication in a registry setting unless it's a specific endpoint.
- Propensity Matched Comparison: This was a retrospective statistical comparison of mortality data, not an adjudication process of individual cases.
5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study Was Done, and the Effect Size of How Much Human Readers Improve with AI vs. Without AI Assistance
No, an MRMC comparative effectiveness study involving AI assistance for human readers was not done. The DuraGraft device is a flushing and storage solution, not an AI-powered diagnostic or assistive tool. The studies described evaluate the biological and clinical effectiveness of the solution itself, not the performance of human readers with or without AI.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
No, a standalone algorithm-only performance study was not done. As mentioned above, the DuraGraft device is a biological solution, not an algorithm. Its performance is evaluated through biological assays, bench testing, and clinical outcomes in patients.
7. The Type of Ground Truth Used
-
DuraGraft Prospective Randomized Study:
- Clinical Outcomes: Vein graft occlusion, MACE events (death, MI, repeat revascularization, angina, arrhythmia, shortness of breath), Fitzgibbon classification of stenosis, and anatomic parameters (wall thickness, focal narrowing) via MDCT. These are established through clinical events and objective imaging measurements.
- Adjudication: Implied for safety outcomes, suggesting expert review.
-
DuraGraft EU Registry:
- Clinical Outcomes: MACE (death, MI, repeat revascularization), stroke, all-cause death. These are derived from patient records in a post-market registry.
-
Propensity Matched Comparison (STS Registry):
- Mortality: Established by linkage to the US National Death Index (NDI), which is a definitive source for death records.
-
Nonclinical/Bench Studies (Pachuk et al., Korkmaz-Icoz et al., Aschacher et al.):
- Biological Ground Truth: Graft cell viability, morphology (H&E staining, Immunohistochemistry for CD31 and vWF), vasoactive physiologic arterial dysfunction, endothelial and sub-endothelial structure, reactive oxygen species, oxidation-reduction potential. These are experimentally determined biological endpoints.
8. The Sample Size for the Training Set
The concept of a "training set" is not applicable here as the DuraGraft device is a therapeutic solution, not a machine learning algorithm. The studies described are for validation and efficacy of the biological product.
9. How the Ground Truth for the Training Set Was Established
As there is no training set for an algorithm, this question is not applicable. The device's development would have involved extensive pre-clinical research and formulation, guided by biological principles and experimental observations, rather than an ML-model training paradigm.
N/A