Effects of the V1a Agonist FE 202158 in Patients With Septic Shock

Infusion Proof-of-concept Trial Investigating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Ascending Doses of FE 202158 in Patients With Vasodilatory Hypotension in Early Septic Shock

The purpose of this trial was to examine the safety and tolerability, pharmacokinetics of FE 202158 and to assess whether it can stabilize blood pressure and reduce vascular (blood vessel) leakage. FE 202158 had previously been tested in healthy volunteers.

This was a multi-centre, double-blind, randomized, placebo-controlled, parallel group trial investigating the safety, tolerability, pharmacokinetics, and pharmacodynamics of FE 202158 (using three ascending doses) in patients with vasodilatory hypotension in early septic shock, when given as continuous infusion for up to 7 days.

The trial comprised of three treatment arms where FE 202158 was administered in 1.25 ng, 2.5 ng and 3.75 ng dose, respectively. A placebo arm was also included in the trial where patients received isotonic saline.

Efficacy of FE 202158 was determined by evaluating its ability to maintain mean arterial pressure (MAP) >60 mmHg and its modulating effect on inflammatory markers. Effects of FE 202158 on other variables like vital signs, morbidity, mortality and pulmonary function were also determined.

Inclusion Criteria:

• Signed informed consent form by the patient or a legal representative according to local regulations
• Man or woman 18 years of age or older
• Proven or suspected infection
• Low blood pressure
• Signs of decreased circulation in the tissues
• Willing to use an adequate barrier method or hormonal method of contraception, if not abstinent, from the day of informed consent to one week after the end of infusion of study medication.

Exclusion Criteria:

• Present or a history (within the last 5 years) of acute coronary syndrome (myocardial infarction or unstable angina). Patients who have been asymptomatic for 6 months after coronary revascularisation are eligible.
• Hypovolaemia suspected on clinical grounds, e.g. cold extremities with delayed capillary filling, low cardiac filling pressure, marked systolic or pulse pressure variation or positive leg raising test.
• Known or suspected cardiac failure
• Pregnancy or breastfeeding
• Any cause of hypotension other than early septic shock
• Use of vasopressin or terlipressin for blood pressure support during the current hospital admission
• Proven or suspected acute mesenteric ischemia, as judged by the investigator
• Known episode of septic shock within 1 month prior to randomisation
• Underlying chronic heart disease
• Traumatic brain injury
• Present hospitalisation with burn injury
• Symptomatic peripheral vascular disease including Raynaud's syndrome
• Previously randomized in this trial
• Intake of an investigational drug within the last 3 months (or longer if judged by the Investigator to possibly influence the outcome of the current study)
• Known participation in another clinical trial
• Considered by the investigator to be unsuitable to participate in the trial for any other reason