TNF-α Antagonists Mitigate Systemic Inflammatory Response After Cardiac Arrest.

NCT07176754 | Not Yet Recruiting DMC

• 1 other identifier: IRB00006761-M20250549
• Study Type: interventional
• Target: 208
• Locations: 0 countries
• Sites: N/A

Brief Summary

The investigators assessed the effect of TNF-α antagonism within 6 hours of return of spontaneous circulation on 30-day mortality in patients who remained comatose after cardiopulmonary resuscitation (CPR) following cardiac arrest . In addition, the investigators explored the role of this treatment in modulating the systemic inflammatory response and its potential impact on 90- and 180-day morbidity and mortality and neurological outcomes.

Conditions

Cardiac Arrest (CA); Post Cardiac Arrest Syndrome

Keywords

cardiac arrest; post cardiac arrest syndrome; TNF-α antagonism

Outcome Measures

Primary Outcomes (1)

• 30-day survival rate

  All-cause survival rate of patients on day 30 after randomization.

  30 days after randomization.

Secondary Outcomes (3)

• Rate of good neurological function assessed by Modified Rankin scale neurologic function scores and cerebral performance category scores

  30 days, 3 months, and 6 months after randomization

• prolong follow-up survival rate

  3 months and 6 months after randomization

• systematic scoring

  24 hours (h), 48 hours, 72 hours and 1 week after randomization

Study Arms (2)

intervention group

EXPERIMENTAL

Patients in the intervention group received a TNF-α antagonist (infliximab) within 6 hours after return of spontaneous circulation(ROSC).

Drug: Infliximab

control group

PLACEBO COMPARATOR

Patients in the control group received 250 mL of 0.9% sodium chloride injection as a placebo.

Drug: Sodium chloride injection USP, 0.9% (placebo)

Interventions

Infliximab DRUG

The TNF-α antagonist (infliximab) used by the experimenter was manufactured by Hisun Biopharmaceuticals Ltd. under the trade name "anbaite".The dosage was administered at 5 mg/kg, dissolved in 250 mL of 0.9% sodium chloride injection, and delivered via intravenous infusion over 2 hours.

intervention group

Sodium chloride injection USP, 0.9% (placebo) DRUG

Patients in the control group received 250 mL of 0.9% sodium chloride injection as a placebo, administered via intravenous infusion over 2 hours.

control group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients aged ≥18 years;
• Patients with suspected cardiogenic cardiac arrest;
• Patients with comatose state after ROSC (Glasgow Coma Scale \[GCS\] score \<9);
• Patients with Return of spontaneous circulation (ROSC) sustained for \>20 minutes;

You may not qualify if:

• Cardiac arrest due to trauma;
• Suspected or confirmed hemorrhagic or ischemic stroke;
• Pregnancy;
• Cardiac arrest without witnessed collapse;
• Admission body temperature \<30°C;
• Persistent cardiogenic shock (defined as systolic blood pressure \<90 mmHg despite aggressive intervention during screening);
• Any underlying disease with an expected survival of \<180 days;
• Pre-existing severe neurological dysfunction before cardiac arrest (e.g., Cerebral Performance Category \[CPC\] 3-4);
• Time from ROSC to randomization exceeding 4 hours;
• Left ventricular ejection fraction (LVEF) \<35% after ROSC;
• Known hypersensitivity to TNF-α antagonist components;
• Known tuberculosis or other active infections;
• Known poor prognosis (as determined by the investigator);
• History of liver cirrhosis;
• History of chronic heart failure with NYHA functional class III-IV.

Sponsors & Collaborators

• Peking University Third Hospital: lead
• Peking University First Hospital: collaborator
• Peking University People's Hospital: collaborator
• Peking University Shenzhen Hospital: collaborator
• Qilu Hospital of Shandong University: collaborator
• Jiangsu Provincial People's Hospital: collaborator
• Hunan Provincial People's Hospital: collaborator
• Sichuan Provincial People's Hospital: collaborator
• People's Hospital of Guangxi Zhuang Autonomous Region: collaborator
• People's Hospital of Xinjiang Uygur Autonomous Region: collaborator
• Renmin Hospital of Wuhan University: collaborator

Related Publications (13)

• Zhou Y, Fan R, Botchway BOA, Zhang Y, Liu X. Infliximab Can Improve Traumatic Brain Injury by Suppressing the Tumor Necrosis Factor Alpha Pathway. Mol Neurobiol. 2021 Jun;58(6):2803-2811. doi: 10.1007/s12035-021-02293-1. Epub 2021 Jan 27.

  PMID: 33501626 RESULT

• Chen AQ, Fang Z, Chen XL, Yang S, Zhou YF, Mao L, Xia YP, Jin HJ, Li YN, You MF, Wang XX, Lei H, He QW, Hu B. Microglia-derived TNF-alpha mediates endothelial necroptosis aggravating blood brain-barrier disruption after ischemic stroke. Cell Death Dis. 2019 Jun 20;10(7):487. doi: 10.1038/s41419-019-1716-9.

  PMID: 31221990 RESULT

• Yin Z, Raj D, Saiepour N, Van Dam D, Brouwer N, Holtman IR, Eggen BJL, Moller T, Tamm JA, Abdourahman A, Hol EM, Kamphuis W, Bayer TA, De Deyn PP, Boddeke E. Immune hyperreactivity of Abeta plaque-associated microglia in Alzheimer's disease. Neurobiol Aging. 2017 Jul;55:115-122. doi: 10.1016/j.neurobiolaging.2017.03.021. Epub 2017 Mar 27.

  PMID: 28434692 RESULT

• Cain BS, Meldrum DR, Dinarello CA, Meng X, Joo KS, Banerjee A, Harken AH. Tumor necrosis factor-alpha and interleukin-1beta synergistically depress human myocardial function. Crit Care Med. 1999 Jul;27(7):1309-18. doi: 10.1097/00003246-199907000-00018.

  PMID: 10446825 RESULT

• Stellwagen D, Beattie EC, Seo JY, Malenka RC. Differential regulation of AMPA receptor and GABA receptor trafficking by tumor necrosis factor-alpha. J Neurosci. 2005 Mar 23;25(12):3219-28. doi: 10.1523/JNEUROSCI.4486-04.2005.

  PMID: 15788779 RESULT

• Robertson J, Beaulieu JM, Doroudchi MM, Durham HD, Julien JP, Mushynski WE. Apoptotic death of neurons exhibiting peripherin aggregates is mediated by the proinflammatory cytokine tumor necrosis factor-alpha. J Cell Biol. 2001 Oct 15;155(2):217-26. doi: 10.1083/jcb.200107058. Epub 2001 Oct 15.

  PMID: 11604419 RESULT

• Lu D, Goussev A, Chen J, Pannu P, Li Y, Mahmood A, Chopp M. Atorvastatin reduces neurological deficit and increases synaptogenesis, angiogenesis, and neuronal survival in rats subjected to traumatic brain injury. J Neurotrauma. 2004 Jan;21(1):21-32. doi: 10.1089/089771504772695913.

  PMID: 14987462 RESULT

• Aloisi F, Care A, Borsellino G, Gallo P, Rosa S, Bassani A, Cabibbo A, Testa U, Levi G, Peschle C. Production of hemolymphopoietic cytokines (IL-6, IL-8, colony-stimulating factors) by normal human astrocytes in response to IL-1 beta and tumor necrosis factor-alpha. J Immunol. 1992 Oct 1;149(7):2358-66.

  PMID: 1382099 RESULT

• Annborn M, Dankiewicz J, Erlinge D, Hertel S, Rundgren M, Smith JG, Struck J, Friberg H. Procalcitonin after cardiac arrest - an indicator of severity of illness, ischemia-reperfusion injury and outcome. Resuscitation. 2013 Jun;84(6):782-7. doi: 10.1016/j.resuscitation.2013.01.004. Epub 2013 Jan 8.

  PMID: 23313427 RESULT

• Tae HJ, Kang IJ, Lee TK, Cho JH, Lee JC, Shin MC, Kim YS, Cho JH, Kim JD, Ahn JH, Park JH, Kim IS, Lee HA, Kim YH, Won MH, Lee YJ. Neuronal injury and tumor necrosis factor-alpha immunoreactivity in the rat hippocampus in the early period of asphyxia-induced cardiac arrest under normothermia. Neural Regen Res. 2017 Dec;12(12):2007-2013. doi: 10.4103/1673-5374.221157.

  PMID: 29323039 RESULT

• Nolan JP, Neumar RW, Adrie C, Aibiki M, Berg RA, Bottiger BW, Callaway C, Clark RS, Geocadin RG, Jauch EC, Kern KB, Laurent I, Longstreth WT, Merchant RM, Morley P, Morrison LJ, Nadkarni V, Peberdy MA, Rivers EP, Rodriguez-Nunez A, Sellke FW, Spaulding C, Sunde K, Hoek TV. Post-cardiac arrest syndrome: epidemiology, pathophysiology, treatment, and prognostication. A Scientific Statement from the International Liaison Committee on Resuscitation; the American Heart Association Emergency Cardiovascular Care Committee; the Council on Cardiovascular Surgery and Anesthesia; the Council on Cardiopulmonary, Perioperative, and Critical Care; the Council on Clinical Cardiology; the Council on Stroke. Resuscitation. 2008 Dec;79(3):350-79. doi: 10.1016/j.resuscitation.2008.09.017. Epub 2008 Oct 28.

  PMID: 18963350 RESULT

• Mentzelopoulos SD, Zakynthinos SG. Post-cardiac arrest syndrome: pathological processes, biomarkers and vasopressor support, and potential therapeutic targets. Resuscitation. 2017 Dec;121:A12-A14. doi: 10.1016/j.resuscitation.2017.10.013. Epub 2017 Oct 18. No abstract available.

  PMID: 29055751 RESULT

• Zheng J, Lv C, Zheng W, Zhang G, Tan H, Ma Y, Zhu Y, Li C, Han X, Yan S, Pan C, Zhang J, Hou Y, Wang C, Bian Y, Liu R, Cheng K, Ma J, Zheng Z, Song R, Wang M, Gu J, McNally B, Ong MEH, Chen Y, Xu F; BASIC-OHCA Coordinators and Investigators. Incidence, process of care, and outcomes of out-of-hospital cardiac arrest in China: a prospective study of the BASIC-OHCA registry. Lancet Public Health. 2023 Dec;8(12):e923-e932. doi: 10.1016/S2468-2667(23)00173-1. Epub 2023 Sep 16.

  PMID: 37722403 RESULT

MeSH Terms

Conditions

Heart Arrest; Post-Cardiac Arrest Syndrome

Interventions

Infliximab

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Reperfusion Injury; Vascular Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Qingbian Ma

CONTACT

15611908229; maqingbian@126.com

MQingbian

CONTACT

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 4, 2025
• First Posted: September 16, 2025
• Study Start: October 1, 2025
• Primary Completion (Estimated): July 31, 2028
• Study Completion (Estimated): October 31, 2028
• Last Updated: September 16, 2025

Record last verified: 2025-06