Infusion of Prostacyclin (Iloprost) vs Placebo for 72-hours in Patients With Septic Shock Suffering From Organ Failure

Efficacy and Safety of 72-hour Infusion of Prostacyclin (1 Nanogram(ng)/Kilo(kg)/Minute(Min)) in Patients With Septic Shock Induced Endotheliopathy - a Multicentre Randomized, Placebo-controlled, Blinded, Investigator-initiated Trial"

Patrocinadores

Patrocinador principal: Jakob Stensballe, MD, PhD

Colaborador: Innovation Fund Denmark
Independent Research Fund Denmark

Fuente Rigshospitalet, Denmark
Resumen breve

The purpose of this trial is to investigate the efficacy and safety of continuous intravenous administration of low dose iloprost versus placebo for 72-hours, in up to a total of 380 patients with septic shock suffering from organ failure.

The study hypothesis is that iloprost may be beneficial as an endothelial rescue treatment as it is anticipated to deactivate the endothelium and restore vascular integrity in septic shock patients suffering from organ failure caused by endothelial breakdown, ultimately improving survival.

Descripción detallada

Patients with the most severe type of sepsis, those with septic shock have a mortality rate between 30% to 45% due to multiple organ failure. The poor outcome of shocked patients, and especially those with sepsis, may by related to microvascular endothelial dysfunction. Evidence support that iloprost infusion significantly improved endothelial function and integrity,

The main objective in this trial is to investigate whether continuous infusion of lov dose iloprost at a dose of 1 ng/kg/min for 72-hours is safe and significantly reduce organ failure score in the intensive care unit (ICU) compared to infusion of placebo in patients with septic shock induced endotheliopathy (SHINE).

Patients that are eligible for this trial will be temporarily incompetent due to acute severe illness relating to septic shock, therefore informed consent will be obtained from a scientific guardian. Next-of kin and subsequently the patient will co-sign as soon as possible hereafter. During the trial, patient will be give continuous infusion of low dose iloprost or placebo for 72 hours as well as additional blood samples will be obtained daily for the first 72 hours. Follow up on organ failure, mortality and quality of life will be performed on dag 28 and 90.

This trial is conducted in accordance with the Helsinki 2 Declaration and International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, Guideline for Good Clinical Practice (ICH-GCP) and in compliance with the protocol. As part of the quality assurance on-site monitoring visit will be performed by the an independent GCP-unit including source data verification. Standard Operation Procedure (SOP) to address protocol specific procedures such as data collection and adverse event reporting are developed.

The number of patients participating is based on a power calculation using the data on mean daily SOFA score from a recent randomized, double blind, placebo controlled clinical trial in patients with septic shock: Levosimendan for the prevention of acute organ dysfunction in sepsis (LeoPARD). If the true effect of the intervention is a reduction in mean daily SOFA score of 20% (relative) and providing the trial with 90% power to detect this difference at a significance level of 0.05 will require a sample size of 380 patients.

A pre-planned, blinded interim analysis will be performed after 200 patients have been included in the trial and followed for 90 days.

Estado general Recruiting
Fecha de inicio October 30, 2019
Fecha de Terminación September 30, 2023
Fecha de finalización primaria September 30, 2022
Fase Phase 2/Phase 3
Tipo de estudio Interventional
Resultado primario
Medida Periodo de tiempo
Modified Sequential Organ Failure Assessment (SOFA) Up to 90 days after randomization
Resultado secundario
Medida Periodo de tiempo
28 and 90-day mortality Day 28 and 90 after randomization
Vasopressor free days Until ICU discharge, maximun 90 days after randomization
Mechanical ventilation free days Until ICU discharge, maximun 90 days after randomization
Renal replacement free days Until ICU discharge, maximun 90 days after randomization
Serious adverse reactions (SARs) Until day 7 after randomization
Serious adverse events (SAEs) Until day 7 after randomization
Inscripción 380
Condición
Intervención

Tipo de intervención: Drug

Nombre de intervención: Iloprost

Descripción: Continuously infusion for 72 hours. treatment dose 1 ng/kg/min

Etiqueta de grupo de brazo: Iloprost

Otro nombre: Iloprost infusion

Tipo de intervención: Drug

Nombre de intervención: Isotonic saline

Descripción: Continuously infusion for 72 hours.

Etiqueta de grupo de brazo: Placebo

Otro nombre: Isotonic saline infusion

Elegibilidad

Criterios:

Inclusion Criteria:

All the following criteria must be fulfilled:

1. Adult intensive care patients (age ≥ 18 years)

2. Septic shock defined according to the Sepsis-3 criteria:

- suspected or documented infection

- persisting hypotension requiring vasopressors to maintain a mean arterial blood pressure of 65 mmHg or above

- Lactate level of 2 mmol/L or above despite fluid therapy within the last 3 hours at screening

3. Soluble thrombomodulin (sTM) above 10 ng/mL

Exclusion Criteria:

Patients who fulfil any of the following criteria will be excluded:

1. Withdrawal from active therapy

2. Pregnancy

3. Known hypersensitivity to iloprost.

4. Life-threatening bleeding as defined by the treating physician

5. Known severe heart failure (New York Heart Association (NYHA) class IV)

6. Suspected acute coronary syndrome

7. Previously included in this trial

8. Septic shock for more than 12 hours at the time of screening

9. Informed consent cannot be obtained

10. Included in other clinical trials with prostacyclin within 90 days

Género: All

Edad mínima: 18 Years

Edad máxima: N/A

Voluntarios Saludables: No

Oficial general
Apellido Papel Afiliación
Morten Bestle, MD, PhD Principal Investigator Nordsjaelands Hospital
Contacto general

Apellido: Jakob Stensballe, MD, PhD

Teléfono: +45 3545 8587

Email: [email protected]

Ubicación
Instalaciones: Estado: Contacto:
Dept. of Anaesthesia and Intensive Care, Bispebjerg Hospital | Copenhagen, Denmark Recruiting Niels E Clausen, MD
Dept. of Intensive Care, Copenhagen University Hospital, Rigshospitalet | Copenhagen, Denmark Recruiting Anders Perner, MD, PhD
Dept. of Intensive Care, Copenhagen University Hospital Herlev | Herlev, Denmark Recruiting Peter Søe-Jensen, MD
Dept. of Anaesthesia and Intensive Care, Nordsjaelands Hospital | Hillerød, Denmark Recruiting Morten Bestle, MD, PhD
Dept. of Anaesthesia and Intensive Care, Hvidovre Hospital | Hvidovre, Denmark Recruiting Klaus T Kristiansen, MD
Ubicacion Paises

Denmark

Fecha de verificación

January 2020

Fiesta responsable

Tipo: Sponsor-Investigator

Afiliación del investigador: Rigshospitalet, Denmark

Nombre completo del investigador: Jakob Stensballe, MD, PhD

Título del investigador: Sponsor

Tiene acceso ampliado No
Condición Examinar
Número de brazos 2
Grupo de brazo

Etiqueta: Iloprost

Tipo: Experimental

Descripción: Patients randomized to active treatment (n=190 patients) will receive continuous infusion of iloprost for 72 hours after inclusion or until discharge to ward or death, whichever comes first.

Etiqueta: Placebo

Tipo: Placebo Comparator

Descripción: Patients randomized to placebo treatment (n=190 patients) will receive continuous infusion of placebo for 72 hours after inclusion or until discharge to ward or death, whichever comes first.

Acrónimo COMBAT-SHINE
Datos del paciente No
Información de diseño del estudio

Asignación: Randomized

Modelo de intervención: Parallel Assignment

Descripción del modelo de intervención: Randomization in 2 parallel arms Adaptive phase 2b/3 trial

Propósito primario: Treatment

Enmascaramiento: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Descripción de enmascaramiento: Patient, investigator, outcome assessor and care provider will be blinded.

Fuente: ClinicalTrials.gov