Limitations of the interpretation and extrapolation of clinical trial data in kidney transplant recipients.

OBJECTIVE

The risks and benefits of the participation of kidney transplant recipients in randomized clinical trials (RCTs) investigating new immunosuppressive therapies are unknown.

DESIGN AND

SETTING

We included patients from 12 prospective phase II/III RCTs randomized to the experimental (G1, n=319) or standard-of-care internal control group (G2, n=118). We constructed two additional external control groups with (G3, n=319) or without (G4, n=319) matching inclusion/exclusion criteria based on transplant date. The primary outcome analysis was the composite clinical efficacy failure, defined as biopsy-proven acute rejection (BPAR), graft loss, death, or loss to follow-up 12 months after kidney transplantation.

RESULTS

Survival free of composite clinical efficacy failure was higher among participants in RCT, without difference between experimental or standard-of-care therapy (80∙3 vs 78∙0 vs 69∙9 vs 66∙1%, P<.001), respectively. Patient (98.1 vs 99.2 vs 96.9 vs 91.8 P<.001) and graft (94.0 vs 98.3 vs 90.9 vs 82.4) survivals were also higher in G1 compared to G4, but no differences in survival free of BPAR were observed (85.3 vs 78.8 vs 82.8 vs 81.2 P>.05), respectively.

CONCLUSION

These findings suggested that new treatments investigated in kidney transplant recipients are not associated with detectable harm compared to standard of care.