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.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by coronavirus 2
(SARS-CoV-2) and, thus, being a novel cause of sepsis. The disease was first identified in
2019 in Wuhan, the capital of Hubei, China, and has since spread globally, resulting in the
2019-20 coronavirus pandemic. Common symptoms include fever, cough and shortness of breath,
muscle pain and sputum production. While many cases result in mild symptoms, some progress to
pneumonia and multi-organ failure. In particular COVID-19 is associated with ARDS with
respiratory failure and high mortality.

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 the
need of respiratory support in the intensive care unit (ICU) compared to infusion of placebo
in patients with COVID-19 induced pulmonary endotheliopathy (SHINE).

Patients that are eligible for this trial will be temporarily incompetent due to acute severe
illness relating to respiratory failure, 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 given continuous infusion of low dose
iloprost or placebo for 72 hours and additional blood samples will be obtained at baseline
and at 24 hours. Follow up on respiratory failure and mortality 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 days
alive and free from mechanical ventilation in the ICU within 28 days from a randomized,
double blind, placebo controlled clinical trial in patients with acute respiratory distress
syndrome ARDS (NTC 02622724).

The number of patients may be increased if required for regulatory approval for this
indication.