Key papers ✓ 2✗ 1~ 3? 2

• ✗ Negative human RCTBMJ · 2025

  The efficacy and safety of thymosin α1 for sepsis (TESTS): multicentre, double blinded, randomised, placebo controlled, phase 3 trial.

  Humans1,106 peopleRandomizedPlacebo-controlledDouble-blindSubcutaneous injection every 12 hours for up to 7 days; primary outcome at 28 days

  Multicentre, double-blind, randomised, placebo-controlled phase 3 trial (1:1)

  TESTS phase 3 trial in 1,089 adults with sepsis: 28-day mortality was 23.4% with thymosin alpha-1 vs 24.1% with placebo (HR 0.99); no secondary or safety outcome differed.

  Key result28-day mortality 127 (23.4%) with thymosin alpha-1 vs 132 (24.1%) with placebo (HR 0.99, 95% CI 0.77 to 1.27; P=0.93)

  Study details

  Studied

  Adults aged 18-85 with sepsis (Sepsis-3 criteria), 22 centres in China

  Compared with

  Placebo

  Main outcome

  28-day all-cause mortality

  Sample

  1106 adults randomized (thymosin n=552, placebo n=554); 1089 in modified intention-to-treat analysis

  Authors' conclusion

  This trial found no clear evidence that thymosin alpha-1 decreases 28-day all-cause mortality in adults with sepsis. No secondary or safety outcome differed significantly.

  Limitations

  Prespecified subgroups (age, diabetes) suggested possible differential effects, not confirmatory.

  DOI 10.1136/bmj-2024-082583PubMed 39814420Free full text
• ~ Mixed meta-analysisFront Cell Infect Microbiol · 2025

  Efficacy of thymosin α1 for sepsis: a systematic review and meta-analysis of randomized controlled trials.

  Humans11 RCTs (967 patients thymosin, 960 control)11 RCTs pooled28-day mortality

  Systematic review and meta-analysis of RCTs with trial sequential analysis and heterogeneity-of-treatment-effect analysis

  Meta-analysis of sepsis RCTs found a possible 28-day mortality reduction overall, but no significant benefit in high-quality or multicenter trials, and the total sample was judged inadequate.

  Key resultOverall OR 0.73 (95% CI 0.59-0.90, P=0.003); high-quality subgroup OR 0.82 (0.65-1.03, P=0.09); multi-center subgroup OR 0.86 (0.68-1.08, P=0.20)

  Study details

  Studied

  Patients with sepsis

  Compared with

  Control

  Main outcome

  28-day mortality

  Authors' conclusion

  Thymosin alpha-1 has the potential to decrease 28-day mortality in sepsis, but efficacy differs among subgroups; trial sequential analysis suggests the current sample size is inadequate.

  Limitations

  Benefit not seen in high-quality or multicenter subgroups; sample size inadequate per TSA.

  DOI 10.3389/fcimb.2025.1673959PubMed 40969554Free full text
  Figure 3
• ~ Mixed meta-analysisInflammopharmacology · 2023

  The efficacy of thymosin alpha-1 therapy in moderate to critical COVID-19 patients: a systematic review, meta-analysis, and meta-regression.

  Humans8 studies8 studies pooled

  Systematic review, meta-analysis and meta-regression

  Meta-analysis of 8 studies in moderate-to-critical COVID-19: lower mortality with thymosin alpha-1 (RR 0.59) but very high heterogeneity and no difference in need for ventilation or length of stay; authors call for RCTs.

  Key resultMortality RR 0.59 (95% CI 0.37-0.93, p=0.02, I2=84%); mechanical ventilation RR 0.83 (0.48-1.44, p=0.51); length of stay MD 2.32 (-0.93 to 5.58, p=0.16)

  Study details

  Studied

  Patients with moderate to critical COVID-19

  Compared with

  Placebo

  Main outcome

  Mortality, need for mechanical ventilation, hospital length of stay

  Authors' conclusion

  Thymosin alpha-1 may reduce mortality in moderate to critical COVID-19; randomized clinical trials are still required to verify the findings.

  Limitations

  High heterogeneity (I2 84%).

  DOI 10.1007/s10787-023-01354-2PubMed 37845598
• ~ Mixed meta-analysisAntiviral Res · 2008

  Comparison of the efficacy of thymosin alpha-1 and interferon alpha in the treatment of chronic hepatitis B: a meta-analysis.

  Humans199 people4 RCTs pooled6 months treatment and 6 months post-treatment follow-up

  Meta-analysis of randomized controlled trials, thymosin alpha-1 vs interferon alpha

  Meta-analysis of 4 RCTs (199 chronic hepatitis B patients): thymosin alpha-1 was not better than interferon alpha at end of therapy but had higher virological and biochemical response 6 months after treatment.

  Key resultEnd of treatment complete response OR 0.54 (0.30, 0.97); 6 months post-treatment OR 3.71 (2.05, 6.71) virological, 3.12 (1.74, 5.62) biochemical, 2.69 (1.47, 4.91) complete response

  Study details

  Studied

  Patients with chronic hepatitis B

  Compared with

  Interferon alpha

  Main outcome

  Virological, biochemical and complete response

  Sample

  4 RCTs, 199 chronic hepatitis B patients

  Authors' conclusion

  Compared with interferon alpha, benefit of thymosin alpha-1 was not immediately significant at end of therapy, but responses tended to accumulate gradually after therapy.

  Limitations

  Only four small trials; results mostly applicable to HBeAg-negative patients.

  DOI 10.1016/j.antiviral.2007.10.014PubMed 18078676
• ✓ Positive meta-analysisFront Immunol · 2025

  Thymosin alpha 1 alleviates inflammation and prevents infection in patients with severe acute pancreatitis through immune regulation: a systematic review and meta-analysis.

  Humans706 people5 RCTs pooled

  Systematic review and meta-analysis of randomized controlled studies

  Meta-analysis in severe acute pancreatitis: thymosin alpha-1 reduced infections outside the pancreas (RR 0.56) and illness-severity scores but not hospital stay; authors call for more validation.

  Key resultExtrapancreatic infections RR 0.56 (95% CI 0.40-0.78, P=0.0005); CD4+ MD 4.53 (3.02-6.04); hospital stay MD -4.22 (-11.53 to 3.10, P=0.26); APACHE II MD -1.52 (-2.22 to -0.83)

  Study details

  Studied

  Patients with severe acute pancreatitis

  Compared with

  Non-thymosin alpha-1 control

  Main outcome

  CD4+ cells, CD4+/CD8+ ratio, CRP, extrapancreatic infection, hospital stay, APACHE II

  Sample

  5 RCTs, 706 patients with severe acute pancreatitis

  Authors' conclusion

  Thymosin alpha-1 may regulate immune balance and exert anti-inflammatory and infection-preventive effects in SAP; more research is needed to validate the results.

  Limitations

  Only five trials; no significant reduction in hospital stay or lung infections.

  DOI 10.3389/fimmu.2025.1571456PubMed 40599771Free full text
  Figure 4
• ? Inconclusive human RCTJ Infect Dis · 2023

  A Pilot Trial of Thymalfasin (Thymosin-α-1) to Treat Hospitalized Patients With Hypoxemia and Lymphocytopenia Due to Coronavirus Disease 2019 Infection.

  Humans49 peopleRandomizedOpen-label

  Prospective open-label randomized pilot trial

  Open-label randomized pilot in 49 hospitalized COVID-19 patients: clinical recovery was not significantly improved, though CD4+ T-cell counts rose faster in one subgroup; serious adverse events were judged unrelated.

  Key resultClinical recovery subdistribution HR 1.48 (95% CI 0.68-3.25) with low-flow oxygen and 1.28 (0.35-4.63) with high-flow oxygen, neither significant; CD4+ T cells rose 3.84 times more by day 5 in low-flow subgroup (P=.01)

  Study details

  Studied

  Hospitalized COVID-19 patients with hypoxemia and lymphocytopenia

  Compared with

  Standard of care

  Main outcome

  Clinical recovery; CD4+ T-cell count

  Sample

  49 patients included in analysis

  Authors' conclusion

  Thymosin alpha-1 increases CD4+ T-cell count faster than standard of care in patients on low-flow oxygen and may have a role in management of such patients.

  Limitations

  Open-label pilot; small; recovery differences not significant.

  DOI 10.1093/infdis/jiac362PubMed 36056913Free full text
• ? Inconclusive human RCTHepatol Int · 2009

  A randomized controlled trial of thymalfasin plus transarterial chemoembolization for unresectable hepatocellular carcinoma.

  Humans25 peopleRandomized24 weeks treatment; survival assessed through 24 months

  Phase II randomized trial

  Phase II trial in 25 patients with unresectable liver cancer: adding thymalfasin to chemoembolization gave numerically better survival and fewer bacterial infections, but differences were not significant.

  Key resultResponders 8/14 (57.1%) vs 5/11 (45.5%) (P=1.0); median overall survival 110.3 vs 57.0 weeks (P=0.45); no bacterial infections with thymalfasin vs 4 with TACE alone

  Study details

  Studied

  Patients with unresectable hepatocellular carcinoma

  Compared with

  TACE alone

  Main outcome

  Response (transplant eligibility or no progression through week 72) and survival

  Sample

  25 patients (TACE + thymalfasin n=14, TACE alone n=11)

  Authors' conclusion

  TACE plus thymalfasin gave numerically higher survival and response rates with fewer bacterial infections; larger trials are needed.

  Limitations

  Small phase II trial; differences not statistically significant.

  DOI 10.1007/s12072-009-9132-3PubMed 19669251Free full text
• ✓ Positive human trialVaccine · 2012

  Thymosin-alpha 1 (Zadaxin) enhances the immunogenicity of an adjuvated pandemic H1N1v influenza vaccine (Focetria) in hemodialyzed patients: a pilot study.

  Humans94 peopleImmune response assessed through day 168

  Pilot clinical trial: vaccine alone vs vaccine + thymosin alpha-1 (3.2 mg or 6.4 mg)

  Pilot in 94 hemodialysis patients: adding thymosin alpha-1 to H1N1 flu vaccination improved antibody responses vs vaccine alone, with no related adverse events.

  Key resultBoth vaccine + thymosin alpha-1 groups had better HI GMT and GMR on day 21 than vaccine alone; CHMP criteria fully met in thymosin groups; no AE related to thymosin alpha-1

  Study details

  Studied

  Hemodialysis patients receiving H1N1v pandemic influenza vaccine

  Compared with

  Vaccine only

  Main outcome

  Hemagglutination inhibition (HI) geometric mean titer/ratio and seroconversion

  Sample

  94 patients in ITT population (82 per protocol, 99 safety)

  Authors' conclusion

  Thymosin alpha-1 enhanced the immunogenicity of the pandemic influenza vaccine and was safe and well tolerated; larger hemodialyzed populations need study.

  Limitations

  Pilot study; larger studies needed.

  DOI 10.1016/j.vaccine.2011.12.014PubMed 22178096

Reported side effects

Human trials, including a 1,089-patient placebo-controlled sepsis trial, reported no excess of adverse events vs control; no specific side effects were described in the abstracts reviewed.

49 registered human trials (12 active)

✓ positive · ✗ negative · ~ mixed · ? inconclusive, judged on each paper's own main outcome. Grades: A strong human evidence → D little or none. Papers and verdicts are drawn from PubMed, Europe PMC and Russian journals (CyberLeninka); not medical advice.