TANDEM TRIAL: a factorial randomised controlled trial of dose and review schedule of bevacizumab (Avastin) for neovascular macular degeneration in the East Midlands

Foss, Alexander J E; Haydock, Rebecca; Childs, Margaret; Duley, Lelia; Empeslidis, Theo; Dhar-Munshi, Sushma; Montgomery, Alan; Ogollah, Reuben; Ozolins, Mara; Tesha, Paul; Mitchell, Eleanor

Abstract

Objective: Neovascular age-related macular degeneration (nAMD) causes damage to the macula and severe vision loss. Bevacizumab is the most cost-effective nAMD treatment. The TANDEM trial was designed to determine whether, in patients with nAMD, low-dose bevacizumab is non-inferior to the standard dose in terms of visual deterioration and whether a bimonthly regimen is non-inferior to monthly, treatment as required, regimens.

Methods: This was a multicentre, 2×2 factorial, double-masked, non-inferiority randomised trial with patients considered eligible if they met the National Institute for Health and Care Excellence criteria for nAMD treatment with ranibizumab. Participants were randomly assigned to standard (1.25 mg) or low (0.625 mg) dose bevacizumab and either monthly or bimonthly review regimen. The primary outcome was time to vision deterioration, defined as reduction of ≥15 letters (three lines) during the loading phase (visual acuity scores at visits B and C compared with the initial visit A), or ≥6 letters (one line) during the maintenance phase (visual acuity scores at subsequent visits compared with mean vision at visits A–C).

Results: In total 812 participants (918 eyes) were randomised into the trial. The low dose showed some evidence of being non-inferior to standard dose (HR 1.07; 95% CI 0.80 to 1.42), however, there was no strong evidence of bimonthly review being non-inferior to monthly review (HR 1.45; 95% CI 1.09 to 1.94). There was no difference in visual acuity when assessed at 9 months and no major differences in the frequency of serious adverse events or reactions between the groups.

Conclusion: The standard dose of bevacizumab can be halved without compromising efficacy. Bimonthly review cannot be considered to be no worse than monthly review.

Citation

Foss, A. J. E., Haydock, R., Childs, M., Duley, L., Empeslidis, T., Dhar-Munshi, S., Montgomery, A., Ogollah, R., Ozolins, M., Tesha, P., & Mitchell, E. (2020). TANDEM TRIAL: a factorial randomised controlled trial of dose and review schedule of bevacizumab (Avastin) for neovascular macular degeneration in the East Midlands. BMJ Open Ophthalmology, 5(1), Article e000588. https://doi.org/10.1136/bmjophth-2020-000588

• Journal Article Type: Article
• Acceptance Date: Nov 10, 2020
• Online Publication Date: Dec 8, 2020
• Publication Date: 2020-12
• Deposit Date: Dec 10, 2020
• Publicly Available Date: Dec 11, 2020
• Journal: BMJ Open Ophthalmology
• Print ISSN: 2397-3269
• Publisher: BMJ Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 5
• Issue: 1
• Article Number: e000588
• DOI: https://doi.org/10.1136/bmjophth-2020-000588
• Keywords: Ophthalmology
• Public URL: https://nottingham-repository.worktribe.com/output/5053447
• Publisher URL: https://bmjophth.bmj.com/content/5/1/e000588