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Compound monograph · evidence extract

Thymosin beta-4 in atherosclerotic cardiovascular disease and cardiovascular risk reduction — evidence extract

The Institute's graded assessment of Thymosin beta-4 for atherosclerotic cardiovascular disease and cardiovascular risk reduction, with the contributing trials and the domain-by-domain certainty reasoning.

Document identifier
CEI-MN-032/EV-CVD
Series
Evidence extract
Version
2.0
Published
13 Jun 2023
Last reviewed
13 Dec 2023
Next review
13 Dec 2025
Identifier
10.71829/cei.mono.32
Certainty
Very low
Cycle
2023 Q2

§1Evidence extract: Atherosclerotic cardiovascular disease and cardiovascular risk reduction

§1.1Question and anchor outcome

Population
Established atherosclerotic disease of the coronary, cerebral or peripheral arterial beds, or a risk profile sufficient for enrolment in a cardiovascular outcome trial.
Intervention
Thymosin beta-4, intravenous, subcutaneous or topical in clinical studies
Comparator
As used in each contributing trial; reported per trial rather than pooled across comparator types
Anchor outcome
Three-point major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke)

Additional outcomes the Institute extracts for this indication: Cardiovascular death; All-cause death; Hospitalisation for heart failure.

§1.2Contributing trials

Table 1. Trials contributing to the assessment of Thymosin beta-4 in atherosclerotic cardiovascular disease and cardiovascular risk reduction.

TrialPhaseDesignRandomisedDurationYear
TB4-PH1-CARDIAC1Phase 1 ascending doseSingle and multiple dose2012

§1.3Certainty assessment

Certainty assessment by domainDowngrading decision recorded for each certainty domain.Certainty domainNo concernSeriousVery seriousEffect on ratingRisk of biasno downgradeInconsistencydowngrade one levelIndirectnessno downgradeImprecisionno downgradePublication biasdowngrade two levelsTotal downgrading: 3 levelsVery low certainty
Figure 2. Domain-by-domain certainty assessment for Thymosin beta-4 in atherosclerotic cardiovascular disease and cardiovascular risk reduction. The starting rating for a body of randomised evidence is high; each serious concern reduces it by one level and each very serious concern by two.

Table 2. Reasoning recorded against each certainty domain.

DomainRatingReasoning
Risk of biasNo concernNo serious concern identified in this domain.
InconsistencySeriousEstimates vary in magnitude across contributing trials beyond what chance would produce.
IndirectnessNo concernNo serious concern identified in this domain.
ImprecisionNo concernNo serious concern identified in this domain.
Publication biasVery seriousThe evidence base is small, recent and wholly sponsor-generated.
Overall rating: Very low certainty. The Institute has very little confidence in the effect estimate. The true effect is likely to be substantially different from the estimate. In this series a very low rating most often reflects an absence of controlled human evidence rather than conflicting evidence.

§1.4What this extract does not establish

References cited on this page

References are numbered in order of first citation in this document. Each superscript in the text links to its entry below.

  1. Goldstein AL, Hannappel E, Sosne G, Kleinman HK. Thymosin β4: a multi-functional regenerative peptide. Basic properties and clinical applications. Expert Opinion on Biological Therapy 2012;12(1):37–51. doi:10.1517/14712598.2012.634793 · PMID 22074294
  2. D’Hondt M, Bracke N, Taevernier L, Gevaert B, Verbeke F, Wynendaele E, De Spiegeleer B. Related impurities in peptide medicines. Journal of Pharmaceutical and Biomedical Analysis 2014;101:2–30. doi:10.1016/j.jpba.2014.06.012 · PMID 25044089
  3. Manning MC, Chou DK, Murphy BM, Payne RW, Katayama DS. Stability of protein pharmaceuticals: an update. Pharmaceutical Research 2010;27(4):544–575. doi:10.1007/s11095-009-0045-6 · PMID 20143256

Identifiers are reproduced only where the Institute holds them. Where a digital object identifier or PubMed identifier is not shown, the Institute has recorded the journal and year and has not constructed an identifier.

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