Proteomic Analysis of Serum Samples After Cardiac Arrest: a TTM-trial Substudy

NCT ID: NCT07017374

Last Updated: 2025-06-12

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Total Enrollment: 682 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2025-05-22
• Study Completion Date: 2025-12-31

Brief Summary

Cardiac arrest remains a large contributor to morbidity and mortality. Animal studies suggest an improvement in mortality and neurological function with hypothermia after cardiac arrest, a finding that could not be verified in large clinical trials such as Target Temperature Management after Out-of-hospital Cardiac arrest (TTM) trial. Multimodal neuroprognostication is an important tool for differentiating patients that will recover after cardiac arrest, and currently only one biomarker is in clinical use. The purpose of this study is to explore proteomics profiles in TTM trial patients in order to search for potential novel biomarkers, therapeutic targets, and to explore phenotypes of post-cardiac arrest syndrome.

Detailed Description

Background: A pilot study investigating proteomic profiles from 78 patients from the Target Temperature Management after Out-of-hospital Cardiac arrest (TTM) trial revealed 35 proteins associated to functional outcome, and six proteins associated to targeted temperature management at 33 °C. We plan to investigate proteomic profiles in the full cohort of the previously collected TTM-trial biobank. The aim is to stratify protein profiles based on survival, functional outcome, targeted temperature management, and MIRACLE2 score in order to search for potential novel biomarkers, therapeutic targets, and to explore phenotypes of post-cardiac arrest syndrome.

Methods: All patients with available serum samples at 24, 48, and/or 72 hours after return of spontaneous circulation will be included in the liquid chromatography and tandem mass spectrometry analysis using diaPASEF, combining data-independent-acquisition of spectra with parallel accumulation-serial fragmentation. Statistical analysis will include data normalisation, exploratory principal component analysis, and differential expression analysis. Changes in serum protein abundance will be analysed according to survival and binary functional outcome (modified Rankin Scale 0-3 vs. 4-6) at six-months after randomisation, randomisation to target temperature of 33 °C or 36 °C, and the MIRACLE2 score. Secondary stratifications will include sex, age, time to return of spontaneous circulation, shockable vs. non-shockable initial rhythm, circulatory shock on admission, and presumed cause of death.

Conclusion: This study will provide information about proteomic profiles after cardiac arrest and may give insight for identification of novel biomarkers for prediction of outcome.

Conditions

Cardiac Arrest (CA); Proteomics

Study Design

• Observational Model Type: OTHER
• Study Time Perspective: RETROSPECTIVE

Interventions

Proteomic analysis, targeted temperature management

Biobank serum samples from patients that were included in the TTM trial will be used for proteomic analysis. TTM trial randomised patients to targeted temperature management of 33 °C or 36 °C.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Age ≥ 18 years old
• Out-of-hospital cardiac arrest (OHCA) of presumed cardiac cause
• Return of spontaneous circulation (ROSC)
• Unconsciousness (Glasgow Coma Score < 8) (patients not able to obey verbal commands) after sustained ROSC

Exclusion Criteria

• In-hospital cardiac arrest
• OHCA of presumed non-cardiac cause, e.g. after trauma or dissection/rupture of major artery OR Cardiac arrest caused by initial hypoxia (i.e. drowning, suffocation, hanging).
• Known bleeding diathesis (medically induced coagulopathy (e.g warfarin, clopidogrel) does not exclude the patient).
• Suspected or confirmed acute intracranial bleeding
• Suspected or confirmed acute stroke
• Unwitnessed asystole
• Known limitations in therapy and Do Not Resuscitate-order
• Known disease making 180 days survival unlikely
• Known pre-arrest CPC 3 or 4
• Temperature < 30°C on admission
• > 4 hours (240 minutes) from ROSC to screening
• Systolic blood pressure < 80 mm Hg in spite of fluid loading/vasopressor and/or inotropic medication/intra aortic balloon pump. If the systolic blood pressure (SBP) is recovering during the inclusion window (220 minutes) the patient can be included.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Region Skane

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Niklas Nielsen, Professor, MD

Role: PRINCIPAL_INVESTIGATOR

Lund University, Helsingborg hospital

Locations

Lund University

Lund, Skåne County, Sweden

Countries

Sweden

References

Nielsen N, Wetterslev J, al-Subaie N, Andersson B, Bro-Jeppesen J, Bishop G, Brunetti I, Cranshaw J, Cronberg T, Edqvist K, Erlinge D, Gasche Y, Glover G, Hassager C, Horn J, Hovdenes J, Johnsson J, Kjaergaard J, Kuiper M, Langorgen J, Macken L, Martinell L, Martner P, Pellis T, Pelosi P, Petersen P, Persson S, Rundgren M, Saxena M, Svensson R, Stammet P, Thoren A, Unden J, Walden A, Wallskog J, Wanscher M, Wise MP, Wyon N, Aneman A, Friberg H. Target Temperature Management after out-of-hospital cardiac arrest--a randomized, parallel-group, assessor-blinded clinical trial--rationale and design. Am Heart J. 2012 Apr;163(4):541-8. doi: 10.1016/j.ahj.2012.01.013.

Reference Type: BACKGROUND

PMID: 22520518 (View on PubMed)

Lileikyte G, Bakochi A, Ali A, Moseby-Knappe M, Cronberg T, Friberg H, Lilja G, Levin H, Arman F, Kjellstrom S, Dankiewicz J, Hassager C, Malmstrom J, Nielsen N. Serum proteome profiles in patients treated with targeted temperature management after out-of-hospital cardiac arrest. Intensive Care Med Exp. 2023 Jul 17;11(1):43. doi: 10.1186/s40635-023-00528-0.

Reference Type: BACKGROUND

PMID: 37455296 (View on PubMed)

Nielsen N, Wetterslev J, Cronberg T, Erlinge D, Gasche Y, Hassager C, Horn J, Hovdenes J, Kjaergaard J, Kuiper M, Pellis T, Stammet P, Wanscher M, Wise MP, Aneman A, Al-Subaie N, Boesgaard S, Bro-Jeppesen J, Brunetti I, Bugge JF, Hingston CD, Juffermans NP, Koopmans M, Kober L, Langorgen J, Lilja G, Moller JE, Rundgren M, Rylander C, Smid O, Werer C, Winkel P, Friberg H; TTM Trial Investigators. Targeted temperature management at 33 degrees C versus 36 degrees C after cardiac arrest. N Engl J Med. 2013 Dec 5;369(23):2197-206. doi: 10.1056/NEJMoa1310519. Epub 2013 Nov 17.

Reference Type: BACKGROUND

PMID: 24237006 (View on PubMed)

Other Identifiers

2009/324

Identifier Type: -

Identifier Source: org_study_id