Nature Communications (Dec 2024)

PET-CT outcomes from a randomised controlled trial of rosuvastatin as an adjunct to standard tuberculosis treatment

  • Gail B. Cross,
  • Intan P. Sari,
  • Sarah M. Burkill,
  • Chee Woei Yap,
  • Han Nguyen,
  • Do Quyet,
  • Victoria B. Dalay,
  • Emmanuel Gutierrez,
  • Vincent M. Balanag,
  • Randy J. Castillo,
  • Christina C. Chang,
  • Anthony D. Kelleher,
  • Jim O’Doherty,
  • Nicholas I. Paton

DOI
https://doi.org/10.1038/s41467-024-54419-3
Journal volume & issue
Vol. 15, no. 1
pp. 1 – 11

Abstract

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Abstract Adjunctive rosuvastatin for rifampicin-susceptible pulmonary tuberculosis (rs-PTB) shows no effect on microbiological or radiological outcomes in a phase IIb randomised, controlled trial (NCT04504851). We explore the impact of adjunctive rosuvastatin on 18F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) imaging in a sub-study of 24 participants. Changes in standardised uptake value (SUVmax, SUVmean), Total Metabolic Volume, (TMV), Total Lesion Glycolysis (TLG), cavity diameter and volume, between week 0 and week 8 post-randomisation, are evaluated. Here we show no evidence of difference in the reduction in TLG [median 65.8% for the rosuvastatin group (Q1, Q3 38.6, 94.5) vs 64.3% for standard tuberculosis treatment group (Q1, Q3 −20.0, 81.7), P = 0.32], reduction in cavity volume on CT [median 3.2 cm3 (IQR 11.1, 0.5) for rosuvastatin, 2.2 cm3 (IQR 4.6, 0.7) for control (p = 0.72)], or any other PET-CT parameter measured. We show that the first 8-weeks of standard tuberculosis treatment results in a reduction in the volumetric indices (TLG and TMV), but had little change in SUVmax or SUVmean. Change in TLG and TMV holds promise as biomarkers of tuberculosis treatment response: future PET-CT studies should evaluate their role in predicting relapse-free cure, and the overall role of 18F-FDG-PET-CT as a tool for early-phase tuberculosis clinical trials.