Milrinone Versus Placebo in Patients With Septic Shock

Effect of Milrinone Versus Placebo on Hemodynamics in Patients With Septic Shock; Randomized Control Trial

Sepsis is one of the most serious healthcare problems, worldwide, and financial burdens.

The overall mortality of severe sepsis/septic shock was 44.5-52.6%. A common cause of death is refractory shock and multi-organ failure. Myocardial dysfunction is a relatively common complication of septic shock. This causes a decrease in the amount of cardiac output, resulting in insufficient blood supply to the organ and multi-organ failure and lead to death Early goal-directed therapy began to use dobutamine in patients with septic shock Sepsis Survival Campaign Guideline 2016 recommended drug is dobutamine and an alternative drug is milrinone in septic shock patients with clinical signs of poor tissue perfusion.

Study Overview

• Status: Recruiting
• Conditions: Septic Shock; Cardiac Output
• Intervention / Treatment: Drug: Milrinone

Detailed Description

According to several studies, the use of dobutamine increases the amount of cardiac output but it has also been reported to increase mortality rates too. There are few studies of milrinone in patients with septic shock.

• Study Type: Interventional
• Enrollment (Anticipated): 64
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Surat Tongyoo, Doctor; Phone Number: +6624198534; Email: surat_Ty@yahoo.co.uk
• Study Contact Backup: Name: Suratee Chobngam, Doctor; Phone Number: +66807155065; Email: areefsu123@gmail.com

Study Locations

• Thailand
  • Bangkok, Thailand, 10700
    • Recruiting
    • Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University
    • Contact: Surat Tongyoo, MD; Phone Number: +6624198534; Email: surat_Ty@yahoo.co.uk
  • Songkhla
    • Hat Yai, Songkhla, Thailand, 10700
      • Recruiting
      • Hat Yai hospital
      • Contact: Chutima Jiranakorn, doctor; Phone Number: +66815993377; Email: waitfor027@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients ≥ 18 years old
• Diagnosis Septic Shock from the definition of SEPSIS III in intensive care unit at Siriraj hospital and Hat-Yai hospital
• Receive fluid resuscitation at least 30 ml/kg and/or Vasopressor until mean arterial pressure ≥ 65 mmHg
• Persistence lactate >2mmol/L at 6th hour after resuscitation
• Urine output < 0.5 ml/kg at 6th hour after resuscitation
• Left ventricular ejection fraction (LVEF) < 40 %

Exclusion Criteria:

• Chronic kidney disease stage 5 and denied renal replacement therapy
• Life-threatening tachyarrhythmia before enrolled e.g. Ventricular tachycardia, Ventricular fibrillation
• Patient sign do-not-resuscitation and terminally ill

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Milrinone group; The pharmacist prepares milrinone 20 mg with normal saline solution (NSS) 100 ml then starts dose 0.5 mg/kg/min for up to 12 hours. The doctor performs Echocardiogram before start Milrinone, during infusion, and after 12 hours from stop Milrinone. Other medications or interventions were used or not used depending on own doctor.	Drug: Milrinone; Prepare milrinone 20 mg with NSS 100 ml then starts dose 0.5 mg/kg/min for up to 12 hours.; Other Names: Primacor
PLACEBO_COMPARATOR: Placebo group; The pharmacist uses 100 ml of NSS, packed out in the same format, dose, and administration of the drug were exactly the same as in the milrinone group. The doctor performs Echocardiogram same time as the milrinone group	Drug: Milrinone; Prepare milrinone 20 mg with NSS 100 ml then starts dose 0.5 mg/kg/min for up to 12 hours.; Other Names: Primacor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The change of cardiac output from baseline (before study drug administration) to 6 hours (during study administration)	by echocardiogram or Pulse contour analysis or Thermodilution technique from pulmonary artery catheter	upto 24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intensive care unit (ICU) mortality	Proportion of participant who die during ICU admission	upto 120 days
Hospital mortality	Proportion of participant who die during hospital admission	upto 120 days
28-day mortality	Proportion of participant who die during 28 days after enrollment	upto 28 days
Dose of vasopressor after intervention	present as vasopressor equivalent dose compare before and after intervention, and percent of decrease	upto 7 days
Lactate clearance	lactate level after and before intervention and percent clearance	upto 7 days
Mechanical ventilator free day	day of the patient does not use mechanical ventilator during admission	upto 28 days
Extracorporeal membrane oxygenation (ECMO) or Renal replacement therapy (RRT)	incident of initial ECMO or RRT	upto 28 days
Incident of tachyarrhythmia	Incident of ventricular tachycardia, ventricular fibrillation, Atrial fibrillation	upto 28 days

Collaborators and Investigators

• Sponsor: Mahidol University
• Investigators: Principal Investigator: Surat Tongyoo, Mahidol University

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 1, 2021
• Primary Completion (ANTICIPATED): December 1, 2024
• Study Completion (ANTICIPATED): June 1, 2025

Study Registration Dates

• First Submitted: September 23, 2021
• First Submitted That Met QC Criteria: November 4, 2021
• First Posted (ACTUAL): November 17, 2021

Study Record Updates

• Last Update Posted (ACTUAL): September 15, 2022
• Last Update Submitted That Met QC Criteria: September 13, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Septic shock; Cardiac output; Milrinone; Poor tissue perfusion
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Shock, Septic; Shock; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Protective Agents; Cardiotonic Agents; Phosphodiesterase Inhibitors; Phosphodiesterase 3 Inhibitors; Milrinone
• Other Study ID Numbers: SI 111/2021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymous identification data will be prepared per request, after study publication 6 months.
• IPD Sharing Time Frame: 6 months post study publication
• IPD Sharing Access Criteria: Request to principal investigation, after protocal approval from ethical committee.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No