Objective:

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• The article was retracted due to undisclosed changes to primary endpoint assessments following database lock and trial unblinding.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.

Sources:

• The New England Journal of Medicine
• US Food and Drug Administration