RENAL: TNF-alpha Inhibitor for Improving Renal Dysfunction and Primary Graft Dysfunction After Lung Transplant

Lung Transplant; Complications Clinical Trial

Official title:

RENAL: Randomized Clinical Trial of TNF-alpha Inhibitor for Improving Renal Dysfunction and Primary Graft Dysfunction After Lung Transplant

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT05950724
• Other study ID #: STU00218926
• Status: Enrolling by invitation
• Phase: Early Phase 1
• Start date: September 17, 2023
• Est. completion date: April 2025

Study information

• Verified date: November 2023
• Source: Northwestern University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess whether TNFa antibody use before lung transplant can prevent kidney injury after lung transplant.

Description:

After being informed about the study and potential risks, all patients giving written consent who undergo a lung transplant will be randomized in a 1:1 ratio to either the treatment or control group. Patients randomized to the treatment group will receive one dose of the study drug, Etanercept, via subcutaneous injection just prior to the lung transplant. Patients randomized to the control group will not receive Etanercept. Both groups will receive standard lung transplant care after implantation.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 20
• Est. completion date: April 2025
• Est. primary completion date: April 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Planning to undergo transplantation of the lung at Northwestern Memorial Hospital.
• Willing and able to read, understand, and be capable of giving informed consent.

Exclusion Criteria:

• Previous or current use of TNFa antibody.
• Any condition that, in the opinion of the attending physician, would place the patient at undue risk by participating.

Related Conditions & MeSH terms

• Lung Transplant; Complications
• Primary Graft Dysfunction
• Renal Insufficiency

Intervention

Drug:
• Etanercept Injection [Enbrel]
25 mg subcutaneous injection

Locations

Country	Name	City	State
United States	Northwestern University	Chicago	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Northwestern University

Country where clinical trial is conducted

United States, 

References & Publications (15)

Gerriets V, Goyal A, Khaddour K. Tumor Necrosis Factor Inhibitors. 2023 Jul 3. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from http://www.ncbi.nlm.nih.gov/books/NBK482425/ — View Citation

Gottlieb AB. Tumor necrosis factor blockade: mechanism of action. J Investig Dermatol Symp Proc. 2007 May;12(1):1-4. doi: 10.1038/sj.jidsymp.5650029. — View Citation

Grivennikov SI, Tumanov AV, Liepinsh DJ, Kruglov AA, Marakusha BI, Shakhov AN, Murakami T, Drutskaya LN, Forster I, Clausen BE, Tessarollo L, Ryffel B, Kuprash DV, Nedospasov SA. Distinct and nonredundant in vivo functions of TNF produced by t cells and macrophages/neutrophils: protective and deleterious effects. Immunity. 2005 Jan;22(1):93-104. doi: 10.1016/j.immuni.2004.11.016. — View Citation

Haraoui B. Differentiating the efficacy of the tumor necrosis factor inhibitors. Semin Arthritis Rheum. 2005 Apr;34(5 Suppl1):7-11. doi: 10.1016/j.semarthrit.2005.01.003. — View Citation

Heung LJ, Hohl TM. Inflammatory monocytes are detrimental to the host immune response during acute infection with Cryptococcus neoformans. PLoS Pathog. 2019 Mar 21;15(3):e1007627. doi: 10.1371/journal.ppat.1007627. eCollection 2019 Mar. — View Citation

Hsiao HM, Fernandez R, Tanaka S, Li W, Spahn JH, Chiu S, Akbarpour M, Ruiz-Perez D, Wu Q, Turam C, Scozzi D, Takahashi T, Luehmann HP, Puri V, Budinger GRS, Krupnick AS, Misharin AV, Lavine KJ, Liu Y, Gelman AE, Bharat A, Kreisel D. Spleen-derived classical monocytes mediate lung ischemia-reperfusion injury through IL-1beta. J Clin Invest. 2018 Jul 2;128(7):2833-2847. doi: 10.1172/JCI98436. Epub 2018 May 21. — View Citation

Komaki Y, Yamada A, Komaki F, Kudaravalli P, Micic D, Ido A, Sakuraba A. Efficacy, safety and pharmacokinetics of biosimilars of anti-tumor necrosis factor-alpha agents in rheumatic diseases; A systematic review and meta-analysis. J Autoimmun. 2017 May;79:4-16. doi: 10.1016/j.jaut.2017.02.003. Epub 2017 Feb 13. — View Citation

Kurihara C, Lecuona E, Wu Q, Yang W, Nunez-Santana FL, Akbarpour M, Liu X, Ren Z, Li W, Querrey M, Ravi S, Anderson ML, Cerier E, Sun H, Kelly ME, Abdala-Valencia H, Shilatifard A, Mohanakumar T, Budinger GRS, Kreisel D, Bharat A. Crosstalk between nonclassical monocytes and alveolar macrophages mediates transplant ischemia-reperfusion injury through classical monocyte recruitment. JCI Insight. 2021 Mar 22;6(6):e147282. doi: 10.1172/jci.insight.147282. — View Citation

Meroni PL, Valentini G, Ayala F, Cattaneo A, Valesini G. New strategies to address the pharmacodynamics and pharmacokinetics of tumor necrosis factor (TNF) inhibitors: A systematic analysis. Autoimmun Rev. 2015 Sep;14(9):812-29. doi: 10.1016/j.autrev.2015.05.001. Epub 2015 May 15. — View Citation

Mocci G, Marzo M, Papa A, Armuzzi A, Guidi L. Dermatological adverse reactions during anti-TNF treatments: focus on inflammatory bowel disease. J Crohns Colitis. 2013 Nov;7(10):769-79. doi: 10.1016/j.crohns.2013.01.009. Epub 2013 Mar 1. — View Citation

Roach DR, Bean AG, Demangel C, France MP, Briscoe H, Britton WJ. TNF regulates chemokine induction essential for cell recruitment, granuloma formation, and clearance of mycobacterial infection. J Immunol. 2002 May 1;168(9):4620-7. doi: 10.4049/jimmunol.168.9.4620. — View Citation

Rubbert-Roth A, Atzeni F, Masala IF, Caporali R, Montecucco C, Sarzi-Puttini P. TNF inhibitors in rheumatoid arthritis and spondyloarthritis: Are they the same? Autoimmun Rev. 2018 Jan;17(1):24-28. doi: 10.1016/j.autrev.2017.11.005. Epub 2017 Nov 3. — View Citation

Scaravilli V, Merrino A, Bichi F, Madotto F, Morlacchi LC, Nosotti M, Lissoni A, Rosso L, Blasi F, Pesenti A, Zanella A, Castellano G, Grasselli G. Longitudinal assessment of renal function after lung transplantation for cystic fibrosis: transition from post-operative acute kidney injury to acute kidney disease and chronic kidney failure. J Nephrol. 2022 Sep;35(7):1885-1893. doi: 10.1007/s40620-022-01392-z. Epub 2022 Jul 15. — View Citation

Wajda-Pokrontka M, Nadziakiewicz P, Krauchuk A, Ochman M, Zawadzki F, Przybylowski P. Influence of Fluid Therapy on Kidney Function in the Early Postoperative Period After Lung Transplantation. Transplant Proc. 2022 May;54(4):1115-1119. doi: 10.1016/j.transproceed.2022.02.021. Epub 2022 Apr 13. — View Citation

Zheng Z, Chiu S, Akbarpour M, Sun H, Reyfman PA, Anekalla KR, Abdala-Valencia H, Edgren D, Li W, Kreisel D, Korobova FV, Fernandez R, McQuattie-Pimentel A, Zhang ZJ, Perlman H, Misharin AV, Scott Budinger GR, Bharat A. Donor pulmonary intravascular nonclassical monocytes recruit recipient neutrophils and mediate primary lung allograft dysfunction. Sci Transl Med. 2017 Jun 14;9(394):eaal4508. doi: 10.1126/scitranslmed.aal4508. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Occurrence of kidney dysfunction immediately after lung transplant	Measured by serum creatinine blood tests	Immediately after lung transplant
Primary	Occurrence of kidney dysfunction post-operatively within 1 week after lung transplant	Measured by serum creatinine blood tests	Within 1-7 days after lung transplant
Primary	Occurrence of kidney dysfunction post-operatively within 1 month after lung transplant	Measured by serum creatinine blood tests	Up to 30 days after lung transplant
Secondary	Occurrence of primary graft dysfunction	Measured by arterial blood gas (ABG) blood tests and chest X-rays	Within 3 days post-transplant
Secondary	Length of intensive care unit (ICU) stay	Measured by number of days in the ICU post-transplant	Through study completion, an average of 1 year
Secondary	Length of ventilator use	Measured by number of days on a ventilator post-transplant	Through study completion, an average of 1 year
Secondary	Survival	Alive or dead post-transplant	30 days, 90 days, and one year survival post-transplant