Semaglutide Use in Acute Pulmonary Embolism
Condition: Pulmonary Embolism
MeSH terms: Pulmonary Embolism; Embolism
Study type: Observational

Summary: 
      Evaluation of circulating endothelial inflammatory biomarkers in response to GLP-1 agonist
      Semaglutide in acute pulmonary embolism
    

Detailed description: 
      Study Rationale and risk/benefit analysis

      This GLP-1 intervention study in patients with acute PE represents an original hypothesis in
      a population with unmet clinical need. The results of this study could have important and
      immediate clinical implications in improving outcomes for this patient group. The current
      long-term treatment of acute PE is limited to anticoagulation, and there are no other studies
      investigating different treatment approaches. Vascular inflammation is known to be an
      important factor driving thrombus evolution and vascular remodelling, and therefore exploring
      the utility of targeting vascular inflammation is an important step forward in developing new
      treatment strategies for this common condition.

      We aim to conduct a proof-of-concept open label study with biomarker response to evaluate
      Semaglutide, a GLP-1 agonist, administered as add-on therapy to the standard of care in adult
      patients with acute PE treated in hospital. Outcomes will be compared to a control group who
      will not receive the study drug. The study will recruit adult patients with proximal or large
      clot burden PE with evidence of right ventricular dysfunction on admission. This group has
      the highest risk of impaired clot resolution and of development of long-term complications
      including chronic thromboembolic disease.

      There is a low risk of study drug complications given the extensive availability of human
      clinical trial data with GLP-1 agonists. There is also extensive real-world experience on the
      use of Semaglutide in the clinical investigation of glucose control in diabetes. As the first
      dose of the study drug is administered in hospital, clinical monitoring is optimised and
      common biochemical perturbations (hypoglycaemia) are easily interrogated and acted on by the
      clinical team. Patients who have contraindications to the use of GLP-1 agonists and patients
      currently taking GLP-1 agonists for diabetes mellitus are excluded to reduce the risks
      associated with the study drug even further.

      Trial Objectives and Design

      Trial Objectives

      This proof-of-concept interventional study will comprise three separate but inter-linking
      aims:

      I. Determine the effect of Semaglutide on highly glycosylated CD147- driven vascular
      inflammation in acute PE and GLP-1 receptor expression levels.

      II. Evaluate immunological effects of Semaglutide in patients with acute PE (T cell receptor
      expression/cytokine, chemokine levels).

      III. Determine the impact of Semaglutide on clot resolution and right ventricular recovery
      following acute PE.

      4.2. Primary endpoints Evaluate the change in highly glycosylated CD147 between day 0 and
      following 6 weeks of Semaglutide.

      4.3. Secondary endpoints I. Determine the rate of persistent CTPA or VQ scan perfusion
      defects with Semaglutide.

      II. Change in right ventricular function, FAC andTASPE on echocardiography between day 0 and
      following 6 weeks of Semaglutide.

      III. Change in plasma Cyclophylin A, sCD147, D-dimer, E selectin, VCAM, MMP levels, NTproBNP,
      GLP1-R, Troponin, myeloperoxidase activity.
    

Intervention name(s): Semaglutide
Intervention type(s): Drug
Intervention description(s): Semaglutide in addition to standard of care
Other intervention name(s): None applicable
Observational model: Other
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Acute admission with acute pulmonary embolism
      
Biospecimen description: 
      Patient plasma samples, collected at baseline and at study completion 4 week time-point