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

NCT ID: NCT01000649

Last Updated: 2017-09-25

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

53 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-11-30

Study Completion Date

2011-09-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Septic Shock

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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FE 202158 1.25

Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 1.25 ng/kg/min.

FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.

Group Type EXPERIMENTAL

FE 202158 1.25

Intervention Type DRUG

FE 202158 at dose 1.25 ng/kg/min infused.

FE 202158 2.5

Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 2.5 ng/kg/min.

FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.

Group Type EXPERIMENTAL

FE 202158 2.5

Intervention Type DRUG

FE 202158 at dose 2.5 ng/kg/min infused.

FE 202158 3.75

Patients in the arm received an intravenous infusion for up to 7 days of FE 202158 at an initial rate of 3.75 ng/kg/min.

FE 202158 was provided as an isotonic acetate buffered stock solution of pH 4.0 in vials appropriately diluted with isotonic saline prior to use.

Group Type EXPERIMENTAL

FE 202158 3.75

Intervention Type DRUG

FE 202158 at dose 3.75 ng/kg/min infused.

PLCBO

Patients in the arm received an intravenous infusion for up to 7 days of placebo.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

Isotonic saline infused.

Interventions

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FE 202158 1.25

FE 202158 at dose 1.25 ng/kg/min infused.

Intervention Type DRUG

FE 202158 2.5

FE 202158 at dose 2.5 ng/kg/min infused.

Intervention Type DRUG

FE 202158 3.75

FE 202158 at dose 3.75 ng/kg/min infused.

Intervention Type DRUG

Placebo

Isotonic saline infused.

Intervention Type OTHER

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ferring Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Development Support

Role: STUDY_DIRECTOR

Ferring Pharmaceuticals

Locations

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Christiana Care Health System

Newark, Delaware, United States

Site Status

Baystate Medical Center

Springfield, Massachusetts, United States

Site Status

Division of Education and Research SMDC Health System

Duluth, Minnesota, United States

Site Status

Cooper University Hospital

Camden, New Jersey, United States

Site Status

Mount Sinai School of Medicine

New York, New York, United States

Site Status

Baylor College of Medicine

Houston, Texas, United States

Site Status

Clinique Universitaire St-Luc

Brussels, , Belgium

Site Status

Erasme Hospital (Free University of Brussels)

Brussels, , Belgium

Site Status

University Hospital Vrije Universiteit

Brussels, , Belgium

Site Status

Service des Soins Intensits

Dinant, , Belgium

Site Status

Royal Columbian Hospital

Vancouver, , Canada

Site Status

St. Paul´s Hospital

Vancouver, , Canada

Site Status

Bispebjerg Hospital

Bispebjerg, , Denmark

Site Status

Rigshospitalet

Copenhagen, , Denmark

Site Status

Hillerød Hospital

Hillerød, , Denmark

Site Status

Hvidovre Hospital

Hvidovre, , Denmark

Site Status

Countries

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United States Belgium Canada Denmark

References

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Russell JA, Vincent JL, Kjolbye AL, Olsson H, Blemings A, Spapen H, Carl P, Laterre PF, Grundemar L. Selepressin, a novel selective vasopressin V1A agonist, is an effective substitute for norepinephrine in a phase IIa randomized, placebo-controlled trial in septic shock patients. Crit Care. 2017 Aug 15;21(1):213. doi: 10.1186/s13054-017-1798-7.

Reference Type RESULT
PMID: 28807037 (View on PubMed)

Rehberg S, Yamamoto Y, Sousse L, Bartha E, Jonkam C, Hasselbach AK, Traber LD, Cox RA, Westphal M, Enkhbaatar P, Traber DL. Selective V(1a) agonism attenuates vascular dysfunction and fluid accumulation in ovine severe sepsis. Am J Physiol Heart Circ Physiol. 2012 Nov 15;303(10):H1245-54. doi: 10.1152/ajpheart.00390.2012. Epub 2012 Sep 7.

Reference Type DERIVED
PMID: 22961865 (View on PubMed)

Other Identifiers

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EudraCT: 2009-010798-19

Identifier Type: -

Identifier Source: secondary_id

FE 202158 CS02

Identifier Type: -

Identifier Source: org_study_id