Hypotension in the Weaning From Vasopressor Drugs

Septic Shock Clinical Trial

Official title:

Incidence of Hypotension in the Weaning From Vasopressor Drugs

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05506319
• Other study ID #: 57213022.0.0000.5530
• Status: Recruiting
• Phase: N/A
• Start date: April 4, 2022
• Est. completion date: October 2023

Study information

• Verified date: July 2022
• Source: Hospital Nossa Senhora da Conceicao
• Contact: Cassio Mallmann, MD
• Phone: 55 51 997284427
• Email: casmallmann[@]yahoo.com.br
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 78
• Est. completion date: October 2023
• Est. primary completion date: July 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Hypotension
• Septic Shock

Intervention

Other:
• Norepinephrine
The patients will be randomized for the initial suspension of norepinephrine (norepinephrine group). Interruption means suspension for at least 24 hours.
• Vasopressin
The patients will be randomized for the initial suspension of vasopressin (vasopressin group). Interruption means suspension for at least 24 hours.

Locations

Country	Name	City	State
Brazil	Hospital Nossa Senhora da Conceicao	Porto Alegre	RS

Sponsors (1)

Lead Sponsor	Collaborator
Hospital Nossa Senhora da Conceicao

Country where clinical trial is conducted

Brazil, 

References & Publications (21)

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. — View Citation

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. — View Citation

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. — View Citation

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. Review. — View Citation

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, Ce — View Citation

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 S — View Citation

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. — View Citation

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 — View Citation

Hotchkiss RS, Karl IE. The pathophysiology and treatment of sepsis. N Engl J Med. 2003 Jan 9;348(2):138-50. Review. — View Citation

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/s13054-01 — View Citation

Landry DW, Oliver JA. The pathogenesis of vasodilatory shock. N Engl J Med. 2001 Aug 23;345(8):588-95. Review. — View Citation

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. d — View Citation

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: 10.1 — View Citation

Russell JA, Walley KR, Singer J, Gordon AC, Hébert 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 — View Citation

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. — View Citation

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 C — View Citation

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. — View Citation

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/s41598-021-9632 — View Citation

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. — View Citation

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. 2021 May 12:8971900211015080. doi: 10.1177/08971900211015080. [Epub ahead of print] — View Citation

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): — View Citation

* Note: There are 21 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of hypotension	Evaluation of the incidence of hypotension in the first 24 hours after discontinuation of one of the vasoactive drugs: norepinephrine or vasopressin. It is defined as hypotension the drop in mean blood pressure below 65 mmHg, triggering one or more of the following measures: a) administration of crystalloid or colloid aliquot, b) dose increase of the remaining vasoactive drug or c) re-establishment of the drug vasoactive paused.	The first 24 hours after the start of reduction of one of the vasopressors.
Secondary	Mortality	Evaluation of the mortality in first 28 days after discontinuation of one of the vasoactive drugs.	Mortality in a 28-day follow-up, from the beginning of the reduction of one of the vasopressors.
Secondary	Length of stay in intensive care unit	Evaluation of the length of stay in intensive care unit.	In a 28-day follow-up, from the beginning of reduction of one of the vasopressors.
Secondary	Time of use of the vasoactive drugs	Quantify the time spent using vasoactive drugs after the removal of the first drug (norepinephrine or vasopressin) in days.	Follow-up of up to 7 days, from the beginning of reduction of one of the vasopressors.
Secondary	Incidence of arrhythmias	Quantify the incidence of arrhythmias with hemodynamic repercussions in 24 hours after withdrawal of the first drug (norepinephrine or vasopressin). This group includes events in which hemodynamic worsening required electrical or chemical cardioversion.	The first 24 hours after the start of reduction of one of the vasopressors.
Secondary	Incidence of hemodialysis	Quantify the incidence of hemodialysis, independent of dialysis modality, excluding patients on dialysis chronic.	The first 72 hours after the start of reduction of one of the vasopressors.

External Links

•   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.