Hypotension in the Weaning From Vasopressor Drugs

NCT ID: NCT05506319

Last Updated: 2025-03-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

78 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-05-01

Study Completion Date

2023-06-30

Brief Summary

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Although there is consensus in the literature on hemodynamic management of septic shock in the resuscitation phase, the best way to conduct the weaning of vasopressor drugs in the stabilization phase remains open. The present study aims to study the incidence of hypotension in the weaning phase of vasopressor drugs- norepinephrine and vasopressin.

Detailed Description

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A randomized, open-case clinical trial with 2 arms will be conducted: initial suspension of norepinephrine (norepinephrine group) versus initial vasopressin (vasopressin group).

The selection of patients who will participate in the study will be for convenience. The randomization of the patients will be done by opaque envelopes 1:1, grouped into blocks, generated by random numbers.

The study will be carried out in the intensive care unit of a tertiary hospital in Southern Brazil, taking into account the clinical and surgical patients. In the intensive care unit, after randomization, patients will be identified by posters, attached to the bed. The titration of vasoactive drugs will be criterion of the assistant team.

Conditions

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Septic Shock

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

A randomized, parallel, open-case clinical trial.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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norepinephrine group

Initial suspension of norepinephrine.

Group Type EXPERIMENTAL

Norepinephrine

Intervention Type OTHER

The patients will be randomized for the initial suspension of norepinephrine (norepinephrine group).

vasopressin group

Initial suspension of vasopressin.

Group Type EXPERIMENTAL

Vasopressin

Intervention Type OTHER

The patients will be randomized for the initial suspension of vasopressin (vasopressin group).

Interventions

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Norepinephrine

The patients will be randomized for the initial suspension of norepinephrine (norepinephrine group).

Intervention Type OTHER

Vasopressin

The patients will be randomized for the initial suspension of vasopressin (vasopressin group).

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* Patients with septic shock, according to the definitions of SEPSIS - 3: septic and hypotensive patients, demanding use of vasoactive drug and lactate greater than 2 mmol/L (18 mg/dL).
* Patients admitted to the intensive care unit.
* Patients in need of associated use of norepinephrine and vasopressin.

Exclusion Criteria

* Patients in whom discontinuation of norepinephrine or vasopressin has been given by decision of the assistant team, from a perspective of prioritizing palliative care.
* Patients using a combination of a third drug, with the effect of predominantly vasopressor - adrenaline.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hospital Nossa Senhora da Conceicao

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Cassio Mallmann, MD

Role: PRINCIPAL_INVESTIGATOR

[email protected]

Locations

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Hospital Nossa Senhora da Conceicao

Porto Alegre, Rio Grande do Sul, Brazil

Site Status

Countries

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Brazil

References

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Landry DW, Oliver JA. The pathogenesis of vasodilatory shock. N Engl J Med. 2001 Aug 23;345(8):588-95. doi: 10.1056/NEJMra002709. No abstract available.

Reference Type RESULT
PMID: 11529214 (View on PubMed)

Evans L, Rhodes A, Alhazzani W, Antonelli M, Coopersmith CM, French C, Machado FR, Mcintyre L, Ostermann M, Prescott HC, Schorr C, Simpson S, Wiersinga WJ, Alshamsi F, Angus DC, Arabi Y, Azevedo L, Beale R, Beilman G, Belley-Cote E, Burry L, Cecconi M, Centofanti J, Coz Yataco A, De Waele J, Dellinger RP, Doi K, Du B, Estenssoro E, Ferrer R, Gomersall C, Hodgson C, Hylander Moller M, Iwashyna T, Jacob S, Kleinpell R, Klompas M, Koh Y, Kumar A, Kwizera A, Lobo S, Masur H, McGloughlin S, Mehta S, Mehta Y, Mer M, Nunnally M, Oczkowski S, Osborn T, Papathanassoglou E, Perner A, Puskarich M, Roberts J, Schweickert W, Seckel M, Sevransky J, Sprung CL, Welte T, Zimmerman J, Levy M. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. Crit Care Med. 2021 Nov 1;49(11):e1063-e1143. doi: 10.1097/CCM.0000000000005337. No abstract available.

Reference Type RESULT
PMID: 34605781 (View on PubMed)

Russell JA, Walley KR, Singer J, Gordon AC, Hebert PC, Cooper DJ, Holmes CL, Mehta S, Granton JT, Storms MM, Cook DJ, Presneill JJ, Ayers D; VASST Investigators. Vasopressin versus norepinephrine infusion in patients with septic shock. N Engl J Med. 2008 Feb 28;358(9):877-87. doi: 10.1056/NEJMoa067373.

Reference Type RESULT
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Der-Nigoghossian C, Hammond DA, Ammar MA. Narrative Review of Controversies Involving Vasopressin Use in Septic Shock and Practical Considerations. Ann Pharmacother. 2020 Jul;54(7):706-714. doi: 10.1177/1060028020901521. Epub 2020 Jan 20.

Reference Type RESULT
PMID: 31958982 (View on PubMed)

Russell JA, Fjell C, Hsu JL, Lee T, Boyd J, Thair S, Singer J, Patterson AJ, Walley KR. Vasopressin compared with norepinephrine augments the decline of plasma cytokine levels in septic shock. Am J Respir Crit Care Med. 2013 Aug 1;188(3):356-64. doi: 10.1164/rccm.201302-0355OC.

Reference Type RESULT
PMID: 23796235 (View on PubMed)

Gordon AC, Wang N, Walley KR, Ashby D, Russell JA. The cardiopulmonary effects of vasopressin compared with norepinephrine in septic shock. Chest. 2012 Sep;142(3):593-605. doi: 10.1378/chest.11-2604.

Reference Type RESULT
PMID: 22518026 (View on PubMed)

Nascente APM, Freitas FGR, Bakker J, Bafi AT, Ladeira RT, Azevedo LCP, Lima A, Machado FR. Microcirculation improvement after short-term infusion of vasopressin in septic shock is dependent on noradrenaline. Clinics (Sao Paulo). 2017 Dec;72(12):750-757. doi: 10.6061/clinics/2017(12)06.

Reference Type RESULT
PMID: 29319721 (View on PubMed)

Yin A, Yamada A, Stam WB, van Hasselt JGC, van der Graaf PH. Quantitative systems pharmacology analysis of drug combination and scaling to humans: the interaction between noradrenaline and vasopressin in vasoconstriction. Br J Pharmacol. 2018 Aug;175(16):3394-3406. doi: 10.1111/bph.14385. Epub 2018 Jul 10.

Reference Type RESULT
PMID: 29859008 (View on PubMed)

Stolk RF, van der Poll T, Angus DC, van der Hoeven JG, Pickkers P, Kox M. Potentially Inadvertent Immunomodulation: Norepinephrine Use in Sepsis. Am J Respir Crit Care Med. 2016 Sep 1;194(5):550-8. doi: 10.1164/rccm.201604-0862CP.

Reference Type RESULT
PMID: 27398737 (View on PubMed)

Hotchkiss RS, Karl IE. The pathophysiology and treatment of sepsis. N Engl J Med. 2003 Jan 9;348(2):138-50. doi: 10.1056/NEJMra021333. No abstract available.

Reference Type RESULT
PMID: 12519925 (View on PubMed)

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.

Reference Type RESULT
PMID: 27483065 (View on PubMed)

Smith SE, Newsome AS, Tackett RL. Prescribing of Pressor Agents in Septic Shock: A Survey of Critical Care Pharmacists. J Pharm Technol. 2019 Oct;35(5):187-193. doi: 10.1177/8755122519846164. Epub 2019 May 8.

Reference Type RESULT
PMID: 34752520 (View on PubMed)

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.

Reference Type RESULT
PMID: 26903338 (View on PubMed)

Bauer SR, Aloi JJ, Ahrens CL, Yeh JY, Culver DA, Reddy AJ. Discontinuation of vasopressin before norepinephrine increases the incidence of hypotension in patients recovering from septic shock: a retrospective cohort study. J Crit Care. 2010 Jun;25(2):362.e7-362.e11. doi: 10.1016/j.jcrc.2009.10.005.

Reference Type RESULT
PMID: 19926252 (View on PubMed)

Hammond DA, McCain K, Painter JT, Clem OA, Cullen J, Brotherton AL, Chopra D, Meena N. Discontinuation of Vasopressin Before Norepinephrine in the Recovery Phase of Septic Shock. J Intensive Care Med. 2019 Oct;34(10):805-810. doi: 10.1177/0885066617714209. Epub 2017 Jun 15.

Reference Type RESULT
PMID: 28618919 (View on PubMed)

Bissell BD, Magee C, Moran P, Bastin MLT, Flannery AH. Hemodynamic Instability Secondary to Vasopressin Withdrawal in Septic Shock. J Intensive Care Med. 2019 Sep;34(9):761-765. doi: 10.1177/0885066617716396. Epub 2017 Jul 28.

Reference Type RESULT
PMID: 28750598 (View on PubMed)

Sacha GL, Lam SW, Duggal A, Torbic H, Reddy AJ, Bauer SR. Hypotension Risk Based on Vasoactive Agent Discontinuation Order in Patients in the Recovery Phase of Septic Shock. Pharmacotherapy. 2018 Mar;38(3):319-326. doi: 10.1002/phar.2082. Epub 2018 Feb 8.

Reference Type RESULT
PMID: 29328496 (View on PubMed)

Jeon K, Song JU, Chung CR, Yang JH, Suh GY. Incidence of hypotension according to the discontinuation order of vasopressors in the management of septic shock: a prospective randomized trial (DOVSS). Crit Care. 2018 May 21;22(1):131. doi: 10.1186/s13054-018-2034-9.

Reference Type RESULT
PMID: 29784057 (View on PubMed)

Bredhold BE, Winters SD, Callison JC Jr, Heidel RE, Allen LM, Hamilton LA. Impact of the Sequence of Norepinephrine and Vasopressin Discontinuation in Patients Recovering From Septic Shock. Hosp Pharm. 2020 Feb;55(1):26-31. doi: 10.1177/0018578718817469. Epub 2018 Dec 5.

Reference Type RESULT
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Taylor A, Jones T, Forehand CC, Smith SE, Dykes H, Newsome AS. Vasopressor Discontinuation Order in Septic Shock With Reduced Left Ventricular Function. J Pharm Pract. 2022 Dec;35(6):879-885. doi: 10.1177/08971900211015080. Epub 2021 May 12.

Reference Type RESULT
PMID: 33977793 (View on PubMed)

Song X, Liu X, Evans KD, Frank RD, Barreto EF, Dong Y, Liu C, Gao X, Wang C, Kashani KB. The order of vasopressor discontinuation and incidence of hypotension: a retrospective cohort analysis. Sci Rep. 2021 Aug 17;11(1):16680. doi: 10.1038/s41598-021-96322-7.

Reference Type RESULT
PMID: 34404892 (View on PubMed)

Mallmann C, Galiotto TMB, de Oliveira MS, Moraes RB. Reduction of norepinephrine versus vasopressin in the stabilization phase of septic shock: RENOVA clinical trial. Med Intensiva (Engl Ed). 2025 Jan 29:502147. doi: 10.1016/j.medine.2025.502147. Online ahead of print.

Reference Type DERIVED
PMID: 39890531 (View on PubMed)

Related Links

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http://seer.ufrgs.br/hcpa/article/view/109542

Borges RB, et al. Power and Sample Size for Health Researchers: uma ferramenta para cálculo de tamanho amostral e poder do teste voltado a pesquisadores da área da saúde.

Other Identifiers

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57213022.0.0000.5530

Identifier Type: -

Identifier Source: org_study_id

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