Genotype stratified adjunctive dexamethasone for tuberculous meningitis in HIV-negative Adults: the LAST ACT trial

Tuberculous meningitis (TBM) is the most severe form of tuberculosis. Adjunctive corticosteroids are recommended for HIV-negative adults, although their benefit appears modest and may depend on host leukotriene A4 hydrolase (LTA4H) genotype. The LAST ACT trial (NCT03100786) was a genotype-stratified, randomised, double-blind, placebo-controlled Phase III trial that evaluated dexamethasone in HIV-negative Vietnamese adults with TBM. A total of 613 adults with LTA4H CC or CT genotypes were randomised to receive dexamethasone or placebo; 89 TT-genotype participants received open-label dexamethasone. The trial found no benefit from adjunctive dexamethasone in CC/CT-genotype participants.
This dataset supports the analysis of a secondary outcome: changes in blood and CSF inflammatory responses. Whole-blood RNA sequencing was performed for 202 participants after quality control (day 0: n=202; day 14: n=188; day 60: n=153). CSF inflammatory proteins were measured in 646 participants using the ..., CSF inflammatory proteins were measured using the Olink Explore 384 Inflammation Panel (Olink Proteomics, Uppsala, Sweden). Olink measurements were conducted for 675 participants on day 0 (n=675) and day 30 (n=397) at the Human Genomics Facility of the Genetic Laboratory, Department of Internal Medicine, Erasmus MC (Rotterdam, Netherlands). Raw protein expression data were reported as Normalized Protein eXpression (NPX) units, which were log₂-transformed and normalized using the plate control method to minimize technical variation. To correct for batch effects, the NPX values then were further adjusted using the ComBat function from the sva R package.31 Quality control (QC) procedures were conducted at both the sample and protein levels. At the sample level, poor-quality samples were excluded if they exhibited a failure rate of ≥50% across protein assays, as determined by Olink’s internal QC criteria. Outliers were identified via principal component analysis (PCA) and excluded if they d..., # Data From: Genotype stratified adjunctive dexamethasone for tuberculous meningitis in HIV-negative adults: the LAST ACT trial

Dataset DOI: [10.5061/dryad.f1vhhmh7v](10.5061/dryad.f1vhhmh7v)

## Dataset Overview

This dataset contains the source data and codes required to replicate analyses for secondary endpoints - Measurements of blood and cerebrospinal fluid inflammation in the submitted manuscript.

### Principal Investigator Contact Information

```
Name: Thuong Nguyen Thuy Thuong <[e-mail]>
Institution: Oxford University Clinical Research Unit - VN
Email: [e-mail]
```

### Alternate Contact Information

```
Name: Nhat Le Thanh Hoang
Institution: Oxford University Clinical Research Unit - VN
Email: [e-mail]
```

```
Name: Hai Hoang Thanh
Institution: Oxford University Clinical Research Unit - VN
Email: [e-mail]
```

### Funding

This work was supported by Wellcome Investigator award [110179/Z/15/Z] to GET and Wellcome Trust Fellowship in Pub..., All participants provided written informed consent to take part in the study, or, in cases where they were incapacitated, consent was obtained from their legal representatives. The trial protocol was approved by the relevant ethics committees, including the Oxford Tropical Research Ethics Committee (OxTREC 52–16), the Ethics Committees of the Hospital for Tropical Diseases, Pham Ngoc Thach Hospital, and the Vietnam Ministry of Health.
The dataset was de-identified by removing all direct identifiers (e.g., date of birth, participant ID) and replacing them with study-specific codes. Indirect identifiers were reviewed and aggregated, where necessary, to minimize the risk of re-identification. The final dataset contains no information that could reasonably be used to identify individual participants.