Septic Shock Management Guided by Ultrasound: SEPTICUS Trial

NCT ID: NCT04728529

Last Updated: 2021-09-27

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 340 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-09-02
• Study Completion Date: 2023-06-30

Brief Summary

This clinical study aims to compare the recent septic shock management protocol from American College of Critical Care Medicine (ACCM) to Ultrasound-guided Septic Shock Management (USSM) protocol. USSM protocol laid on Doppler ultrasonography to evaluate stroke volume, cardiac index, and systemic vascular resistance in each step of management to decide the proper fluid resuscitation and vasoactive therapy; differs from ACCM protocol which use clinical finding in its early step. ACCM protocol application elicits risk of improper therapy since clinical sign per se often could not describe the certain cardiac output. This can be prevented earlier by USSM protocol. The outcome compared of the two protocols is: mortality rate, clinical parameter, macrocirculation hemodynamic parameter, laboratory microcirculation parameter, and signs of fluid overload. The investigators hypothesized if the USSM protocol had a better outcome and less fluid overload complication.

Detailed Description

This study is a randomized controlled trial to compare the usage of ACCM protocol and USSM protocol in fluid resuscitation for septic shock pediatric patients. The USSM protocol is the intervention, and the ACCM protocol is the control. This study implemented in septic shock pediatric patients treated in the intensive care unit. Each patient will be randomized into 2 groups, the USSM group or the ACCM group. In the initial step, all patient in each group will receive early acute/emergency therapy: oxygen support, vascular access, and fluid resuscitation. The monitoring of the patient including clinical parameters and laboratory examination for both groups, except Doppler ultrasonography that performed in each step of management of the intervention group. The monitoring is performed every 15 minutes in the first hour of resuscitation. If the patient show good response (fluid responsive shock), the monitoring stops in 1 hour. In contrast, if the patient reveal fluid refractory shock, the vasoactive agent will be administered and monitoring continues until 6 hours. All outcome parameters, except mortality rate, will be recorded at 6 hours. The mortality rates will be recorded at 72 hours and time of intensive care discharge.

Sample size in this study was calculated by clinical trial formula for mortality rate with a significance level of 0.05 and study power of 0.2. From the calculation, the subject needed is 170 patients for each group (total 340 subjects). The basic characteristics of the patient will be analyzed descriptively. All parameter data will be analyzed statistically by Statistical Product and Service Solution (SPSS) 20, preceded by normality test and homogeneity test. The study analysis will be intention-to-treat. The mortality rate was analyzed by Kaplan-Meier survival analysis. Data transformation will be performed if needed in case of outlier data or out-of-range results.

Conditions

Septic Shock

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

USSM protocol

patient in the intervention group receive fluid resuscitation and inotropic-vasoactive agent, if needed, in accordance to USSM protocol of fluid resuscitation.

Group Type: EXPERIMENTAL

USSM protocol

Intervention Type: PROCEDURE

In the initial step, all subjects will receive emergency management: oxygen support, vascular access, and fluid therapy. Doppler ultrasonography by Ultrasound Cardiac Output Monitoring (USCOM) is also performed to record initial stroke volume (SV), cardiac index (CI), and systemic vascular resistance (SVR). The initial fluid resuscitation is 20 mL/kg body weight, then the response measured by clinical and USCOM examination. If any improvement of clinical sign and normal SVI, CI, SVR, intervention will be stopped. In contrary, if shock persist, subsequent fluid resuscitation and/or vasoactive therapy will be administered, guided by USCOM.

The therapeutic goal of USCOM: SVI 30-60 mL/m2, CI 3.3-6.0 L/minute/m2, and SVRI 800-1600 d.s/cm5/m2

ACCM protocol

patient in the control group receive fluid resuscitation and inotropic-vasoactive agent, if needed, in accordance to ACCM protocol of fluid resuscitation.

Group Type: EXPERIMENTAL

ACCM protocol

Intervention Type: PROCEDURE

In the initial step, all subjects will receive emergency management: oxygen support, vascular access, and fluid therapy. Doppler ultrasonography by Ultrasound Cardiac Output Monitoring (USCOM) is also performed to record initial stroke volume (SV), cardiac index (CI), and systemic vascular resistance (SVR). The initial fluid resuscitation is 20 mL/kg body weight, then the response measured by clinical. If any improvement of clinical sign, intervention will be stopped. In contrary, if shock persist, subsequent fluid resuscitation and/or vasoactive therapy will be administered, guided by clinical parameter.

Interventions

USSM protocol

In the initial step, all subjects will receive emergency management: oxygen support, vascular access, and fluid therapy. Doppler ultrasonography by Ultrasound Cardiac Output Monitoring (USCOM) is also performed to record initial stroke volume (SV), cardiac index (CI), and systemic vascular resistance (SVR). The initial fluid resuscitation is 20 mL/kg body weight, then the response measured by clinical and USCOM examination. If any improvement of clinical sign and normal SVI, CI, SVR, intervention will be stopped. In contrary, if shock persist, subsequent fluid resuscitation and/or vasoactive therapy will be administered, guided by USCOM.

The therapeutic goal of USCOM: SVI 30-60 mL/m2, CI 3.3-6.0 L/minute/m2, and SVRI 800-1600 d.s/cm5/m2

Intervention Type: PROCEDURE

ACCM protocol

In the initial step, all subjects will receive emergency management: oxygen support, vascular access, and fluid therapy. Doppler ultrasonography by Ultrasound Cardiac Output Monitoring (USCOM) is also performed to record initial stroke volume (SV), cardiac index (CI), and systemic vascular resistance (SVR). The initial fluid resuscitation is 20 mL/kg body weight, then the response measured by clinical. If any improvement of clinical sign, intervention will be stopped. In contrary, if shock persist, subsequent fluid resuscitation and/or vasoactive therapy will be administered, guided by clinical parameter.

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• diagnosed as septic shock according to Pediatric Surviving Campaign (2005)

Exclusion Criteria

• patient with uncorrected congenital heart disease with shunting
• obtain fluid resuscitation before recruitment process
• obtain inotropic-vasoactive agent before recruitment process
• after undergo any heart surgery

• Minimum Eligible Age: 1 Month
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Saptadi Yuliarto

OTHER

Sponsor Role: lead

Responsible Party

Saptadi Yuliarto

Head of Pediatric Emergency and Intensive Care Department

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Saptadi Yuliarto, MD

Role: STUDY_DIRECTOR

University of Brawijaya

Locations

RSUD dr. Saiful Anwar

Malang, East Java, Indonesia

Site Status: RECRUITING

Countries

Indonesia

Central Contacts

Saptadi Yuliarto, MD

Role: CONTACT

saptadiy@ub.ac.id

+6281233053652

Nur Hidayati Azhar, MD

Role: CONTACT

nur.hidayati.azhar@gmail.com

+62 822-4509-9109

Facility Contacts

Saptadi Yuliarto, MD

Role: primary

saptadiy@ub.ac.id

+6281233053652

References

Davis AL, Carcillo JA, Aneja RK, Deymann AJ, Lin JC, Nguyen TC, Okhuysen-Cawley RS, Relvas MS, Rozenfeld RA, Skippen PW, Stojadinovic BJ, Williams EA, Yeh TS, Balamuth F, Brierley J, de Caen AR, Cheifetz IM, Choong K, Conway E Jr, Cornell T, Doctor A, Dugas MA, Feldman JD, Fitzgerald JC, Flori HR, Fortenberry JD, Graciano AL, Greenwald BM, Hall MW, Han YY, Hernan LJ, Irazuzta JE, Iselin E, van der Jagt EW, Jeffries HE, Kache S, Katyal C, Kissoon N, Kon AA, Kutko MC, MacLaren G, Maul T, Mehta R, Odetola F, Parbuoni K, Paul R, Peters MJ, Ranjit S, Reuter-Rice KE, Schnitzler EJ, Scott HF, Torres A Jr, Weingarten-Arams J, Weiss SL, Zimmerman JJ, Zuckerberg AL. American College of Critical Care Medicine Clinical Practice Parameters for Hemodynamic Support of Pediatric and Neonatal Septic Shock. Crit Care Med. 2017 Jun;45(6):1061-1093. doi: 10.1097/CCM.0000000000002425.

Reference Type: BACKGROUND

PMID: 28509730 (View on PubMed)

Weiss SL, Peters MJ, Alhazzani W, Agus MSD, Flori HR, Inwald DP, Nadel S, Schlapbach LJ, Tasker RC, Argent AC, Brierley J, Carcillo J, Carrol ED, Carroll CL, Cheifetz IM, Choong K, Cies JJ, Cruz AT, De Luca D, Deep A, Faust SN, De Oliveira CF, Hall MW, Ishimine P, Javouhey E, Joosten KFM, Joshi P, Karam O, Kneyber MCJ, Lemson J, MacLaren G, Mehta NM, Moller MH, Newth CJL, Nguyen TC, Nishisaki A, Nunnally ME, Parker MM, Paul RM, Randolph AG, Ranjit S, Romer LH, Scott HF, Tume LN, Verger JT, Williams EA, Wolf J, Wong HR, Zimmerman JJ, Kissoon N, Tissieres P. Surviving Sepsis Campaign International Guidelines for the Management of Septic Shock and Sepsis-Associated Organ Dysfunction in Children. Pediatr Crit Care Med. 2020 Feb;21(2):e52-e106. doi: 10.1097/PCC.0000000000002198.

Reference Type: BACKGROUND

PMID: 32032273 (View on PubMed)

Weiss SL, Peters MJ, Alhazzani W, Agus MSD, Flori HR, Inwald DP, Nadel S, Schlapbach LJ, Tasker RC, Argent AC, Brierley J, Carcillo J, Carrol ED, Carroll CL, Cheifetz IM, Choong K, Cies JJ, Cruz AT, De Luca D, Deep A, Faust SN, De Oliveira CF, Hall MW, Ishimine P, Javouhey E, Joosten KFM, Joshi P, Karam O, Kneyber MCJ, Lemson J, MacLaren G, Mehta NM, Moller MH, Newth CJL, Nguyen TC, Nishisaki A, Nunnally ME, Parker MM, Paul RM, Randolph AG, Ranjit S, Romer LH, Scott HF, Tume LN, Verger JT, Williams EA, Wolf J, Wong HR, Zimmerman JJ, Kissoon N, Tissieres P. Surviving sepsis campaign international guidelines for the management of septic shock and sepsis-associated organ dysfunction in children. Intensive Care Med. 2020 Feb;46(Suppl 1):10-67. doi: 10.1007/s00134-019-05878-6.

Reference Type: BACKGROUND

PMID: 32030529 (View on PubMed)

Santhanam I, Sangareddi S, Venkataraman S, Kissoon N, Thiruvengadamudayan V, Kasthuri RK. A prospective randomized controlled study of two fluid regimens in the initial management of septic shock in the emergency department. Pediatr Emerg Care. 2008 Oct;24(10):647-55. doi: 10.1097/PEC.0b013e31818844cf.

Reference Type: BACKGROUND

PMID: 19242131 (View on PubMed)

Ranjit S, Aram G, Kissoon N, Ali MK, Natraj R, Shresti S, Jayakumar I, Gandhi D. Multimodal monitoring for hemodynamic categorization and management of pediatric septic shock: a pilot observational study*. Pediatr Crit Care Med. 2014 Jan;15(1):e17-26. doi: 10.1097/PCC.0b013e3182a5589c.

Reference Type: BACKGROUND

PMID: 24196006 (View on PubMed)

Ceneviva G, Paschall JA, Maffei F, Carcillo JA. Hemodynamic support in fluid-refractory pediatric septic shock. Pediatrics. 1998 Aug;102(2):e19. doi: 10.1542/peds.102.2.e19.

Reference Type: BACKGROUND

PMID: 9685464 (View on PubMed)

Horster S, Stemmler HJ, Strecker N, Brettner F, Hausmann A, Cnossen J, Parhofer KG, Nickel T, Geiger S. Cardiac Output Measurements in Septic Patients: Comparing the Accuracy of USCOM to PiCCO. Crit Care Res Pract. 2012;2012:270631. doi: 10.1155/2012/270631. Epub 2011 Nov 29.

Reference Type: BACKGROUND

PMID: 22191019 (View on PubMed)

Goldstein B, Giroir B, Randolph A; International Consensus Conference on Pediatric Sepsis. International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med. 2005 Jan;6(1):2-8. doi: 10.1097/01.PCC.0000149131.72248.E6.

Reference Type: BACKGROUND

PMID: 15636651 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

University of Brawijaya

Identifier Type: -

Identifier Source: org_study_id