Semaglutide Use in Acute Pulmonary Embolism

Sponsor

Imperial College London (Other)

Overall Status

Completed

CT.gov ID

NCT06118203

Collaborator

(none)

Enrollment

Location

Actual Duration (Months)

1.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Pulmonary Embolism	Drug: Semaglutide

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:

Determine the effect of Semaglutide on highly glycosylated CD147- driven vascular inflammation in acute PE and GLP-1 receptor expression levels.
Evaluate immunological effects of Semaglutide in patients with acute PE (T cell receptor expression/cytokine, chemokine levels).
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.

Change in right ventricular function, FAC andTASPE on echocardiography between day 0 and following 6 weeks of Semaglutide.
Change in plasma Cyclophylin A, sCD147, D-dimer, E selectin, VCAM, MMP levels, NTproBNP, GLP1-R, Troponin, myeloperoxidase activity.

Study Design

Study Type:

Observational

Actual Enrollment :

18 participants

Observational Model:

Other

Time Perspective:

Prospective

Official Title:

Evaluation of Circulating Endothelial Inflammatory Biomarkers in Response to GLP-1 Agonist Semaglutide in Acute Pulmonary Embolism

Actual Study Start Date :

Jan 2, 2022

Actual Primary Completion Date :

Mar 4, 2023

Actual Study Completion Date :

Mar 5, 2023

Arms and Interventions

Arm	Intervention/Treatment
Open label Semaglutide Patients presenting with acute intermediate - high risk PE consenting to participation in drug arm of study	Drug: Semaglutide Semaglutide in addition to standard of care Other Names: None applicable
Control Patients presenting with acute intermediate - high risk PE consenting to participation in control arm of study

Arm

Intervention/Treatment

Open label Semaglutide

Patients presenting with acute intermediate - high risk PE consenting to participation in drug arm of study

Drug: Semaglutide

Semaglutide in addition to standard of care

Other Names:

None applicable

Control

Patients presenting with acute intermediate - high risk PE consenting to participation in control arm of study

Outcome Measures

Primary Outcome Measures

Endothelial biomarker measurement [4 weeks]
Change in plasma CD147 level between baseline and 4 weeks

Secondary Outcome Measures

Plasma proteomics [4 weeks]
Change in plasma proteome between baseline and 4 weeks

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Acute pulmonary embolism

Exclusion Criteria:

Concurrent use of GLP-1 agonist

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Colm McCabe	London		United Kingdom	SW3 6NP

Sponsors and Collaborators

Imperial College London

Investigators

Principal Investigator: Colm McCabe, MD, Imperial College London

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Imperial College London

ClinicalTrials.gov Identifier:

NCT06118203

Other Study ID Numbers:

300440

First Posted:

Nov 7, 2023

Last Update Posted:

Nov 7, 2023

Last Verified:

Nov 1, 2023

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Pulmonary Embolism

Embolism

Study Results

No Results Posted as of Nov 7, 2023