Have You Ever Seen a Clinical Study Like This?
The study is the Agili-C study, sponsored by Israeli-U.S. based CartiHeal Ltd, and funded by Johnson & Johnson, Bioventus, Elron, Accelmed, Access Medical Ventures, aMoon and Peregrine Ventures.
The following table is a comparison of cartilage repair studies BEFORE Agili-C and then the first-of-its-kind Agili-C study – FDA sanctioned.
| BEFORE Agili-C | Agili-C[1] | |
| Age of Patients | Usually up to 55 | Up to 75 |
| Presence of Osteoarthritis | NO | Yes (mild-moderate) |
| Number of Lesions | 1-2 | Up to 3 |
| Type of Defects | Cartilage | Cartilage and ostoechondral |
| Concomitant Procedures | Not allowed | Allowed: meniscectomy and HTO |
| Total Defect Size: | 1-4 cm[2] (usually 2 cm2) | 1-7 cm2 |
| Previous Failed cartilage Treatment | Not allowed[3] | Allowed |
| Control / Comparator: | Microfracture[4] | Microfracture and debridement |
| Malalignment Exclusion? | Yes[5] | No (up to 8⁰) |
| Defect Location: | Single Condyle Only | 1 or 2 Condyles, Condyle & Trochlea, 2 Condyles & Trochlea |
The range of defects is large, just like a typical patient population in any orthopedic clinic.
The age range is huge (21-75 years).
The control arm is, effectively, the current common surgical standard of care, microfracture or debridement—not just microfracture.
The number of defects can be as many as three and malalignment is NOT an exclusion (up to 8°).
“The Agili-C trial is very close to real life,” Dr. Verdonk told OTW. “Randomization is versus current standard of care—either debridement or microfracture. Which is a major advantages of the Agili-C study.”
One of the effects of broad inclusion criteria is that the 250-patient study is enrolling notably quickly. Said Dr. Zaslav: “I’ve never seen a study enroll this fast. We’ve already got nearly 200 patients in about one and a half years, and we need 250 until our first Interim Analysis—which we should probably have before year end. The other studies it took four to five years to enroll this number of patients.”
Because the study includes patients with mild to moderate osteoarthritis and allows randomization against EITHER microfracture or debridement, enrollment has really popped.
The randomization allocation ratio is 2:1—for every two patients randomized to the implant, one is randomized to control.
It should be noted that as in previous studies, young patients with small, focal defects but no arthritis, are receiving microfracture. Older patients with large lesions and mild to moderate osteoarthritis are randomized against debridement (small focal defects with KL=0 cannot be treated with debridement).
Again, Dr. Zaslav: “A lot of people don’t want microfractures, so it’s hard to get enough patients in a study randomized to microfracture alone.”
Dr. Kon explains some of the etiology of this novel study design: “Many surgeons believe that microfracture should not be performed to treat large lesions and in presence of osteoarthritis. Performing microfracture in these patients may enhance joint deterioration and the progression of OA, when drilling into the subchondral bone.”
“In reality most early OA patients are not yet candidates for knee replacements and, therefore, are being treated arthroscopically for mechanical symptomatic relief—and their cartilage lesions are being debrided. Debridement, therefore, is the most commonly performed treatment today for cartilage lesions.”
“The uniqueness of this study is that it mimics almost precisely our current surgical practice.”
If the Agili-C study shows clear superiority over microfracture and debridement for the treatment of joint surface knee lesions it will truly be a landmark event.
