To evaluate the efficacy of avacopan for antineutrophil cytoplasmic antibody-associated vasculitis.
Approach:
Study Design: The ADVOCATE trial was a phase 3 randomized, double-blind, double-dummy study conducted at 143 international centers.
Participants: 331 patients with newly diagnosed or relapsing granulomatosis with polyangiitis or microscopic polyangiitis were randomly assigned to receive either avacopan or a tapering regimen of prednisone.
Endpoints: The coprimary endpoints were remission at week 26 and sustained remission at weeks 26 and 52.
Key Findings:
Avacopan was reported as noninferior to prednisone for remission at week 26 based on the original analysis.
Avacopan was reported as superior to prednisone for sustained remission at week 52 based on the original analysis.
The article was retracted due to undisclosed changes to primary endpoint assessments following database lock and trial unblinding.
Interpretation:
The retraction was prompted by undisclosed readjudication of primary endpoint assessments identified during an FDA investigation.
Limitations:
Undisclosed changes to primary endpoint assessments.
Errors in glucocorticoid dose conversions that were corrected in a subsequent publication.
Conclusion:
The retraction raises questions about the study's findings and the conduct of the trial.
