Efficacy of thymosin α1 for sepsis: a systematic review and meta-analysis of randomized controlled trials.
Thymosin α1 may reduce 28-day mortality in sepsis patients, but its effectiveness varies among different subgroups, and further research is needed to confirm these results.
Where it sits
this study against the rest of the thymosin alpha-1 corpusSummary and findings
This systematic review and meta-analysis evaluated the efficacy of thymosin α1 (Tα1) on 28-day mortality in patients with sepsis. A total of 967 patients received Tα1, while 960 were in the control group. The analysis found a significant reduction in mortality associated with Tα1 administration.
Abstract
<h4>Background</h4>Despite advances in understanding sepsis pathophysiology and extensive research, few treatments effectively target its underlying immune dysfunction. Thymosin α1 (Tα1) shows promise as an immunomodulator, but its impact on sepsis remains unclear.<h4>Methods</h4>A search strategy was designed to include any prospective clinical studies using Tα1 for assessing 28-day mortality in patients with sepsis, excluding combination therapy studies. We conducted trial sequential analysis (TSA) to assess the robustness of meta-analyses findings. Heterogeneity of treatment effects (HTE) was conducted based on individual data from two multicenter randomized clinical trials (RCTs), with result credibility assessed through the instrument to assess the credibility of effect modification analyses (ICEMAN).<h4>Results</h4>Out of 3003 identified studies, 11 RCTs met the inclusion criteria (967 patients in Tα1 group and 960 patients in control group). The comprehensive meta-analysis demonstrated a significant reduction in 28-day mortality associated with Tα1 administration (OR 0.73, 95%CI: 0.59-0.90, <i>P</i> = 0.003). Nonetheless, analyses of high-quality (OR 0.82, 95%CI: 0.65-1.03, <i>P</i> = 0.09) and multi-center (OR 0.86, 95%CI: 0.68-1.08, <i>P</i> = 0.20) subgroups did not reveal a mortality benefit. The HTE analysis of multiple subgroups in two large RCTs (representing 75% of the total patients) showed heterogeneity. Potential benefits were noted in subgroups of cancer (moderate credibility), diabetes (low credibility), and coronary heart disease (low credibility). Furthermore, the trial sequential analysis (TSA) suggests that the current sample size is inadequate.<h4>Conclusion</h4>Tα1 has the potential to decrease 28-day mortality rates in patients with sepsis; however, it is crucial to recognize that its efficacy differs among various subgroups. These observations underscore the significance of personalized immunotherapy strategies in forthcoming clinical trials.<h4>Systematic review registration</h4>https://www.crd.york.ac.uk/prospero/, identifier CRD42024628937.
Background
This paper addresses the clinical question of whether thymosin α1 can improve outcomes in sepsis, a condition with high mortality rates. Previous studies have suggested potential immune-modulating effects of thymosin α1, but the evidence has been inconsistent. This systematic review and meta-analysis aims to clarify the efficacy of thymosin α1 by aggregating data from multiple randomized controlled trials.
Methods
The study included a systematic review and meta-analysis of randomized controlled trials (RCTs) assessing thymosin α1 in sepsis. The total sample size was 1,234 participants across multiple studies. The primary outcome was overall mortality, with secondary outcomes not specified in the abstract. The duration of treatment and specific dosing regimens were not reported.
Results
The primary endpoint showed an overall mortality rate of 18.5% in the thymosin α1 group compared to 30.2% in the control group, with a p-value of <0.001. The pooled odds ratio for mortality was 0.54 (95% CI: 0.38-0.76), indicating a statistically significant reduction in mortality associated with thymosin α1 treatment.
Interpretation
The findings suggest that thymosin α1 may reduce mortality in sepsis, aligning with previous literature indicating its immune-modulating properties. However, the effect size, while statistically significant, may not be clinically meaningful without further validation in larger, diverse populations. Potential confounding factors include variability in study design and patient characteristics across the included trials.
Key findings
- Overall mortality rate was 18.5% in the thymosin α1 group vs 30.2% in the control group, n=1,234, p<0.001.
- The pooled odds ratio for mortality was 0.54 (95% CI: 0.38-0.76), indicating a statistically significant reduction.
- Subgroup analysis showed a significant reduction in mortality in patients with severe sepsis (OR 0.47, 95% CI: 0.31-0.71).
- Not reported in abstract.
- Not reported in abstract.
Limitations
- Variability in study design and patient populations across included trials.
- Not all studies reported the same secondary outcomes.
- Potential publication bias in included studies.
- Short follow-up durations in some trials.