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:10.1038/s41467-024-54419-3

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

Nat Commun. 2024 Dec 2;15(1):10475. doi: 10.1038/s41467-024-54419-3.

Authors

Gail B Cross^{1

2

3

4}, Intan P Sari⁵, Sarah M Burkill⁶, Chee Woei Yap⁷, Han Nguyen^{8

9}, Do Quyet⁸, Victoria B Dalay¹⁰, Emmanuel Gutierrez¹⁰, Vincent M Balanag¹¹, Randy J Castillo¹¹, Christina C Chang¹², Anthony D Kelleher¹³, Jim O'Doherty^{14

15}, Nicholas I Paton^{5

16

17}

Affiliations

¹ National University Hospital, Department of Medicine, Singapore, Singapore. [email protected].
² National University of Singapore, Infectious Disease Translational Research Programme, Singapore, Singapore. [email protected].
³ Kirby Institute, University of New South Wales, Sydney, Australia. [email protected].
⁴ Burnet Institute, Melbourne, Australia. [email protected].
⁵ National University Hospital, Department of Medicine, Singapore, Singapore.
⁶ Singapore Clinical Research Institute, Singapore, Singapore.
⁷ National University Health Systems, Department of Diagnostic Imaging, Singapore, Singapore.
⁸ Vietnam Military Medical University, Respiratory Medicine, Hanoi, Viet Nam.
⁹ Karolinska Institute, Department of Medicine Solna, Stockholm, Sweden.
¹⁰ De La Salle Medical and Health Sciences Institute, Cavite, Philippines.
¹¹ Lung Centre of the Philippines, Quezon City, Philippines.
¹² Monash University, Central Clinical School, Melbourne, Australia.
¹³ Kirby Institute, University of New South Wales, Sydney, Australia.
¹⁴ National University of Singapore, Clinical Imaging Research Centre, Singapore, Singapore.
¹⁵ Siemens Medical Solutions, Malvern, USA.
¹⁶ National University of Singapore, Infectious Disease Translational Research Programme, Singapore, Singapore.
¹⁷ Department of Clinical Research, London School of Hygiene and Tropical Medicine, London, UK.

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.

Publication types

Randomized Controlled Trial
Clinical Trial, Phase II

MeSH terms

Adult
Antitubercular Agents* / therapeutic use
Female
Fluorodeoxyglucose F18*
Humans
Male
Middle Aged
Positron Emission Tomography Computed Tomography* / methods
Rifampin / therapeutic use
Rosuvastatin Calcium* / therapeutic use
Treatment Outcome
Tuberculosis, Pulmonary* / diagnostic imaging
Tuberculosis, Pulmonary* / drug therapy

Substances

Rosuvastatin Calcium
Antitubercular Agents
Fluorodeoxyglucose F18
Rifampin

Abstract

Publication types

MeSH terms

Substances

Grants and funding