Effect of Vasopressin on Kidney and Cardiac Function in Septic Shock

NCT06125184 | Unknown DMC

• 1 other identifier: 200318004
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Septic shock is a syndrome characterized by tissue hypoperfusion and hypotension secondary to an uncontrolled infection. It is a frequent cause of admission to the intensive care unit (ICU) and has an associated mortality around 40%. Around 50 % of septic shock patients exhibit early acute kidney injury and 30 to 40% will require renal replacement therapy. After initial fluid resuscitation most of the patients with septic shock become hyperdynamic but still require norepinephrine (NE) to maintain a mean arterial pressure (MAP) above 65 mmHg. The optimal perfusion pressure may vary, specially in previously hypertensive patients as they may have a shift to the right in their kidney auto-regulatory curve. In a previous study in patients with chronic hypertension and septic shock, increasing MAP from 65 mmHg to 85 mmHg with NE was associated with improved renal function. However, the incidence of tachyarrhythmias increased, associated to the higher NE doses required, which has raised some concerns about the safety of this strategy. In this setting, the addition of vasopressin (AVP), a drug used as a vasopressor but with cathecholamine independent mechanisms, may allow to prevent this side effect by decreasing NE dose requirements. Low doses of AVP appear to be safe and when combined with NE in septic shock patients, it resulted in increased creatinine clearance and decreased use of renal replacement therapy, compared to NE alone. Theoretically, AVP can improve glomerular filtration rate. Therefore, the addition of AVP to NE in previously hypertensive septic shock patients should be a reasonable strategy to improve organ perfusion. Furthermore, AVP could be an important step towards decatecholaminization in the management of septic shock patients. However, its effect on cardiac performance and stroke volume when targeting high MAP is unclear.

Conditions

Kidney Injury, Acute; Cardiac Function Failed

Outcome Measures

Primary Outcomes (1)

• Serum creatinine change from baseline to 24 hours

  Serum creatinine change from baseline to 24hours between patients treated with placebo and vasopressin

  24 hours

Secondary Outcomes (4)

• Lipocalin-2/NGAL change from baseline to 24 hours

  24 hours

• Renal resistive index change from baseline to 24 hours

  24 hours

• Contractility change from baseline to 24 hours

  24 hours

• Serum troponin

  24 hours

Study Arms (2)

Placebo group

PLACEBO COMPARATOR

Mean arterial pressure (MAP) will be increased from 65 mmHg to 85 mmHg with a blind drug (Placebo). If MAP does not increase norepinephrine will be titrated to reach the MAP target (85 mmHg).

Drug: Vasopressor test

Vasopressin group

ACTIVE COMPARATOR

Mean arterial pressure (MAP) will be increased from 65 mmHg to 85 mmHg with a blind drug (Vasopressin at 0.03 IU/min). If MAP does not increase norepinephrine will be titrated to reach the MAP target (85 mmHg).

Drug: Vasopressor test

Interventions

Vasopressor test DRUG

Mean arterial pressure will be increased from 65 mmHg to 85 mmHg to improve organ perfusion pressure.

Placebo group; Vasopressin group

Eligibility Criteria

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

You may qualify if:

• Septic shock diagnosed at ICU admission according to the Sepsis-3
• Mechanical ventilation in place
• Past medical history of chronic hypertension
• Fluid unresponsive status
• Stable norepinephrine dose ≥ 0.1 mcg/kg/min
• Persistent tissular hypoperfusion after initial resuscitation

You may not qualify if:

• Age \< 18 years
• \> 24 h since septic shock diagnosis
• Moderate or severe mitral/aortic disease
• Anticipated surgery during the study period
• Abdominal hypertension grade III
• Pregnancy
• Do-not-resuscitate status

Sponsors & Collaborators

• Pontificia Universidad Catolica de Chile: lead
• FONDECYT de iniciación 11201220: collaborator

Study Sites (1)

Hospital Clínico Pontificia Universidad Católica de Chile

Santiago, Santiago Metropolitan, 7561262, Chile

RECRUITING

Related Publications (30)

• Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):801-10. doi: 10.1001/jama.2016.0287.

  PMID: 26903338 BACKGROUND

• Wu Z, McGoogan JM. Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention. JAMA. 2020 Apr 7;323(13):1239-1242. doi: 10.1001/jama.2020.2648. No abstract available.

  PMID: 32091533 BACKGROUND

• Kellum JA, Chawla LS, Keener C, Singbartl K, Palevsky PM, Pike FL, Yealy DM, Huang DT, Angus DC; ProCESS and ProGReSS-AKI Investigators. The Effects of Alternative Resuscitation Strategies on Acute Kidney Injury in Patients with Septic Shock. Am J Respir Crit Care Med. 2016 Feb 1;193(3):281-7. doi: 10.1164/rccm.201505-0995OC.

  PMID: 26398704 BACKGROUND

• Asfar P, Meziani F, Hamel JF, Grelon F, Megarbane B, Anguel N, Mira JP, Dequin PF, Gergaud S, Weiss N, Legay F, Le Tulzo Y, Conrad M, Robert R, Gonzalez F, Guitton C, Tamion F, Tonnelier JM, Guezennec P, Van Der Linden T, Vieillard-Baron A, Mariotte E, Pradel G, Lesieur O, Ricard JD, Herve F, du Cheyron D, Guerin C, Mercat A, Teboul JL, Radermacher P; SEPSISPAM Investigators. High versus low blood-pressure target in patients with septic shock. N Engl J Med. 2014 Apr 24;370(17):1583-93. doi: 10.1056/NEJMoa1312173. Epub 2014 Mar 18.

  PMID: 24635770 BACKGROUND

• Ince C, Sinaasappel M. Microcirculatory oxygenation and shunting in sepsis and shock. Crit Care Med. 1999 Jul;27(7):1369-77. doi: 10.1097/00003246-199907000-00031.

  PMID: 10446833 BACKGROUND

• Bersten AD, Holt AW. Vasoactive drugs and the importance of renal perfusion pressure. New Horiz. 1995 Nov;3(4):650-61.

  PMID: 8574595 BACKGROUND

• Ferrara G, Kanoore Edul VS, Caminos Eguillor JF, Buscetti MG, Canales HS, Lattanzio B, Gatti L, Ince C, Dubin A. Effects of fluid and norepinephrine resuscitation in a sheep model of endotoxin shock and acute kidney injury. J Appl Physiol (1985). 2019 Sep 1;127(3):788-797. doi: 10.1152/japplphysiol.00172.2019. Epub 2019 Jul 11.

  PMID: 31295071 BACKGROUND

• Textor SC, Novick AC, Tarazi RC, Klimas V, Vidt DG, Pohl M. Critical perfusion pressure for renal function in patients with bilateral atherosclerotic renal vascular disease. Ann Intern Med. 1985 Mar;102(3):308-14. doi: 10.7326/0003-4819-102-3-308.

  PMID: 3970470 BACKGROUND

• Cecconi M, De Backer D, Antonelli M, Beale R, Bakker J, Hofer C, Jaeschke R, Mebazaa A, Pinsky MR, Teboul JL, Vincent JL, Rhodes A. Consensus on circulatory shock and hemodynamic monitoring. Task force of the European Society of Intensive Care Medicine. Intensive Care Med. 2014 Dec;40(12):1795-815. doi: 10.1007/s00134-014-3525-z. Epub 2014 Nov 13.

  PMID: 25392034 BACKGROUND

• Gordon AC, Mason AJ, Thirunavukkarasu N, Perkins GD, Cecconi M, Cepkova M, Pogson DG, Aya HD, Anjum A, Frazier GJ, Santhakumaran S, Ashby D, Brett SJ; VANISH Investigators. Effect of Early Vasopressin vs Norepinephrine on Kidney Failure in Patients With Septic Shock: The VANISH Randomized Clinical Trial. JAMA. 2016 Aug 2;316(5):509-18. doi: 10.1001/jama.2016.10485.

  PMID: 27483065 BACKGROUND

• Patel BM, Chittock DR, Russell JA, Walley KR. Beneficial effects of short-term vasopressin infusion during severe septic shock. Anesthesiology. 2002 Mar;96(3):576-82. doi: 10.1097/00000542-200203000-00011.

  PMID: 11873030 BACKGROUND

• Antonucci E, Fiaccadori E, Donadello K, Taccone FS, Franchi F, Scolletta S. Myocardial depression in sepsis: from pathogenesis to clinical manifestations and treatment. J Crit Care. 2014 Aug;29(4):500-11. doi: 10.1016/j.jcrc.2014.03.028. Epub 2014 Apr 5.

  PMID: 24794044 BACKGROUND

• Boissier F, Razazi K, Seemann A, Bedet A, Thille AW, de Prost N, Lim P, Brun-Buisson C, Mekontso Dessap A. Left ventricular systolic dysfunction during septic shock: the role of loading conditions. Intensive Care Med. 2017 May;43(5):633-642. doi: 10.1007/s00134-017-4698-z. Epub 2017 Feb 15.

  PMID: 28204860 BACKGROUND

• Kellum JA, Sileanu FE, Murugan R, Lucko N, Shaw AD, Clermont G. Classifying AKI by Urine Output versus Serum Creatinine Level. J Am Soc Nephrol. 2015 Sep;26(9):2231-8. doi: 10.1681/ASN.2014070724. Epub 2015 Jan 7.

  PMID: 25568178 BACKGROUND

• Kellum JA, Lameire N; KDIGO AKI Guideline Work Group. Diagnosis, evaluation, and management of acute kidney injury: a KDIGO summary (Part 1). Crit Care. 2013 Feb 4;17(1):204. doi: 10.1186/cc11454.

  PMID: 23394211 BACKGROUND

• Kellum JA, Sileanu FE, Bihorac A, Hoste EA, Chawla LS. Recovery after Acute Kidney Injury. Am J Respir Crit Care Med. 2017 Mar 15;195(6):784-791. doi: 10.1164/rccm.201604-0799OC.

  PMID: 27635668 BACKGROUND

• Manns B, Doig CJ, Lee H, Dean S, Tonelli M, Johnson D, Donaldson C. Cost of acute renal failure requiring dialysis in the intensive care unit: clinical and resource implications of renal recovery. Crit Care Med. 2003 Feb;31(2):449-55. doi: 10.1097/01.CCM.0000045182.90302.B3.

  PMID: 12576950 BACKGROUND

• Rauf AA, Long KH, Gajic O, Anderson SS, Swaminathan L, Albright RC. Intermittent hemodialysis versus continuous renal replacement therapy for acute renal failure in the intensive care unit: an observational outcomes analysis. J Intensive Care Med. 2008 May-Jun;23(3):195-203. doi: 10.1177/0885066608315743.

  PMID: 18474503 BACKGROUND

• Langenberg C, Bellomo R, May C, Wan L, Egi M, Morgera S. Renal blood flow in sepsis. Crit Care. 2005 Aug;9(4):R363-74. doi: 10.1186/cc3540. Epub 2005 May 24.

  PMID: 16137349 BACKGROUND

• Bellomo R, Wan L, Langenberg C, May C. Septic acute kidney injury: new concepts. Nephron Exp Nephrol. 2008;109(4):e95-100. doi: 10.1159/000142933. Epub 2008 Sep 18.

  PMID: 18802375 BACKGROUND

• Thooft A, Favory R, Salgado DR, Taccone FS, Donadello K, De Backer D, Creteur J, Vincent JL. Effects of changes in arterial pressure on organ perfusion during septic shock. Crit Care. 2011;15(5):R222. doi: 10.1186/cc10462. Epub 2011 Sep 21.

  PMID: 21936903 BACKGROUND

• Dubin A, Pozo MO, Casabella CA, Palizas F Jr, Murias G, Moseinco MC, Kanoore Edul VS, Palizas F, Estenssoro E, Ince C. Increasing arterial blood pressure with norepinephrine does not improve microcirculatory blood flow: a prospective study. Crit Care. 2009;13(3):R92. doi: 10.1186/cc7922. Epub 2009 Jun 17.

  PMID: 19534818 BACKGROUND

• Bourgoin A, Leone M, Delmas A, Garnier F, Albanese J, Martin C. Increasing mean arterial pressure in patients with septic shock: effects on oxygen variables and renal function. Crit Care Med. 2005 Apr;33(4):780-6. doi: 10.1097/01.ccm.0000157788.20591.23.

  PMID: 15818105 BACKGROUND

• Hernandez G, Ospina-Tascon GA, Damiani LP, Estenssoro E, Dubin A, Hurtado J, Friedman G, Castro R, Alegria L, Teboul JL, Cecconi M, Ferri G, Jibaja M, Pairumani R, Fernandez P, Barahona D, Granda-Luna V, Cavalcanti AB, Bakker J; The ANDROMEDA SHOCK Investigators and the Latin America Intensive Care Network (LIVEN); Hernandez G, Ospina-Tascon G, Petri Damiani L, Estenssoro E, Dubin A, Hurtado J, Friedman G, Castro R, Alegria L, Teboul JL, Cecconi M, Cecconi M, Ferri G, Jibaja M, Pairumani R, Fernandez P, Barahona D, Cavalcanti AB, Bakker J, Hernandez G, Alegria L, Ferri G, Rodriguez N, Holger P, Soto N, Pozo M, Bakker J, Cook D, Vincent JL, Rhodes A, Kavanagh BP, Dellinger P, Rietdijk W, Carpio D, Pavez N, Henriquez E, Bravo S, Valenzuela ED, Vera M, Dreyse J, Oviedo V, Cid MA, Larroulet M, Petruska E, Sarabia C, Gallardo D, Sanchez JE, Gonzalez H, Arancibia JM, Munoz A, Ramirez G, Aravena F, Aquevedo A, Zambrano F, Bozinovic M, Valle F, Ramirez M, Rossel V, Munoz P, Ceballos C, Esveile C, Carmona C, Candia E, Mendoza D, Sanchez A, Ponce D, Ponce D, Lastra J, Nahuelpan B, Fasce F, Luengo C, Medel N, Cortes C, Campassi L, Rubatto P, Horna N, Furche M, Pendino JC, Bettini L, Lovesio C, Gonzalez MC, Rodruguez J, Canales H, Caminos F, Galletti C, Minoldo E, Aramburu MJ, Olmos D, Nin N, Tenzi J, Quiroga C, Lacuesta P, Gaudin A, Pais R, Silvestre A, Olivera G, Rieppi G, Berrutti D, Ochoa M, Cobos P, Vintimilla F, Ramirez V, Tobar M, Garcia F, Picoita F, Remache N, Granda V, Paredes F, Barzallo E, Garces P, Guerrero F, Salazar S, Torres G, Tana C, Calahorrano J, Solis F, Torres P, Herrera L, Ornes A, Perez V, Delgado G, Lopez A, Espinosa E, Moreira J, Salcedo B, Villacres I, Suing J, Lopez M, Gomez L, Toctaquiza G, Cadena Zapata M, Orazabal MA, Pardo Espejo R, Jimenez J, Calderon A, Paredes G, Barberan JL, Moya T, Atehortua H, Sabogal R, Ortiz G, Lara A, Sanchez F, Hernan Portilla A, Davila H, Mora JA, Calderon LE, Alvarez I, Escobar E, Bejarano A, Bustamante LA, Aldana JL. Effect of a Resuscitation Strategy Targeting Peripheral Perfusion Status vs Serum Lactate Levels on 28-Day Mortality Among Patients With Septic Shock: The ANDROMEDA-SHOCK Randomized Clinical Trial. JAMA. 2019 Feb 19;321(7):654-664. doi: 10.1001/jama.2019.0071.

  PMID: 30772908 BACKGROUND

• Pettila V, Merz T, Wilkman E, Perner A, Karlsson S, Lange T, Hastbacka J, Hjortrup PB, Kuitunen A, Jakob SM, Takala J. Targeted tissue perfusion versus macrocirculation-guided standard care in patients with septic shock (TARTARE-2S): study protocol and statistical analysis plan for a randomized controlled trial. Trials. 2016 Aug 2;17:384. doi: 10.1186/s13063-016-1515-x.

  PMID: 27484695 BACKGROUND

• Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, Kumar A, Sevransky JE, Sprung CL, Nunnally ME, Rochwerg B, Rubenfeld GD, Angus DC, Annane D, Beale RJ, Bellinghan GJ, Bernard GR, Chiche JD, Coopersmith C, De Backer DP, French CJ, Fujishima S, Gerlach H, Hidalgo JL, Hollenberg SM, Jones AE, Karnad DR, Kleinpell RM, Koh Y, Lisboa TC, Machado FR, Marini JJ, Marshall JC, Mazuski JE, McIntyre LA, McLean AS, Mehta S, Moreno RP, Myburgh J, Navalesi P, Nishida O, Osborn TM, Perner A, Plunkett CM, Ranieri M, Schorr CA, Seckel MA, Seymour CW, Shieh L, Shukri KA, Simpson SQ, Singer M, Thompson BT, Townsend SR, Van der Poll T, Vincent JL, Wiersinga WJ, Zimmerman JL, Dellinger RP. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-377. doi: 10.1007/s00134-017-4683-6. Epub 2017 Jan 18.

  PMID: 28101605 BACKGROUND

• Monnet X, Jabot J, Maizel J, Richard C, Teboul JL. Norepinephrine increases cardiac preload and reduces preload dependency assessed by passive leg raising in septic shock patients. Crit Care Med. 2011 Apr;39(4):689-94. doi: 10.1097/CCM.0b013e318206d2a3.

  PMID: 21263328 BACKGROUND

• Persichini R, Silva S, Teboul JL, Jozwiak M, Chemla D, Richard C, Monnet X. Effects of norepinephrine on mean systemic pressure and venous return in human septic shock. Crit Care Med. 2012 Dec;40(12):3146-53. doi: 10.1097/CCM.0b013e318260c6c3.

  PMID: 22926333 BACKGROUND

• Skomedal T, Borthne K, Aass H, Geiran O, Osnes JB. Comparison between alpha-1 adrenoceptor-mediated and beta adrenoceptor-mediated inotropic components elicited by norepinephrine in failing human ventricular muscle. J Pharmacol Exp Ther. 1997 Feb;280(2):721-9.

  PMID: 9023284 BACKGROUND

• Hamzaoui O, Jozwiak M, Geffriaud T, Sztrymf B, Prat D, Jacobs F, Monnet X, Trouiller P, Richard C, Teboul JL. Norepinephrine exerts an inotropic effect during the early phase of human septic shock. Br J Anaesth. 2018 Mar;120(3):517-524. doi: 10.1016/j.bja.2017.11.065. Epub 2017 Nov 21.

  PMID: 29452808 BACKGROUND

MeSH Terms

Conditions

Acute Kidney Injury; Heart Failure

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Heart Diseases; Cardiovascular Diseases

Study Officials

• Emilio Daniel Valenzuela Espinoza, MD

  Pontificia Universidad Catolica de Chile

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Emilio Daniel Valenzuela Espinoza, MD

CONTACT

56965329099; ed.valenzuela.e@gmail.com

Vanesa Oviedo, RN

CONTACT

56977497657; voviedo@uc.cl

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: The statisticians and researcher responsible to perform the measurement will be blinded to the group allocation. Nonetheless, the research nurse responsible for event assignment will not be blinded to the group allocation.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Model Details: Prospective, randomized, double-blinded, controlled clinical trial.

Study Record Dates

• First Submitted: July 27, 2022
• First Posted: November 9, 2023
• Study Start: November 1, 2022
• Primary Completion: October 1, 2024
• Study Completion: January 1, 2025
• Last Updated: November 9, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

CL (1)