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Completed

NCT Number: NCT01000649

Effects of the V1a Agonist FE 202158 in Patients With 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.

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Key information

Conditions

Septic Shock Infections Inflammation Pathologic Processes Pathological Conditions, Signs and Symptoms Sepsis Shock Shock, Septic Systemic Inflammatory Response Syndrome

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Clinique Universitaire St-Luc, Brussels, Belgium

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

FE 202158 1.25

Drug

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

FE 202158 2.5

Drug

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

FE 202158 3.75

Drug

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

Placebo

Other

Isotonic saline infused.

Primary outcomes

  1. Proportion of Patients Maintaining Target Mean Arterial Pressure (MAP) (>60 mmHg) With no Open Label NE (Norepinephrine)

    Time frame: Day 1 up to Day 7

    Data were evaluated for target MAP of ≥ 60 mmHg. A 95% confidence interval (CI) was calculated and presented using Clopper-Pearson method.

    The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.

  2. Proportion of Patients Maintaining Target MAP (>60) Irrespective of Open Label NE

    Time frame: Day 1 up to Day 7

    Data were evaluated for target MAP of ≥ 60 mmHg. A 95% confidence interval (CI) was calculated and presented using Clopper-Pearson method.

    The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.

  3. Cumulative Dose of Open Label NE.

    Time frame: Day 1 up to Day 7

    Cumulative Dose of Open Label NE over 7 days.

    The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.

  4. Infusion Rates of Open Label NE.

    Time frame: Day 1 up to Day 7

    Mean open label NE infusion rate within each predefined time period.

    The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.

Secondary outcomes

  1. Pharmacokinetic (PK) Parameter in Patients : Steady State Concentration

    Time frame: Day 1 up to Day 7

    PK parameters were calculated using nonlinear 2-compartment population PK model with random patient effects on clearance and volume of distribution.

    The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.

  2. PK Parameter in Patients : Time to Steady State

    Time frame: Day 1 up to Day 7

    PK parameters were calculated using nonlinear 2-compartment population PK model with random patient effects on clearance and volume of distribution.

    The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.

  3. PK Parameter in Patients : Clearance

    Time frame: Day 1 up to Day 7

    PK parameters were calculated using nonlinear 2-compartment population PK model with random patient effects on clearance and volume of distribution.

    The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.

  4. PK Parameter in Patients : Steady State Volume of Distribution

    Time frame: Day 1 up to Day 7

    PK parameters were calculated using nonlinear 2-compartment population PK model with random patient effects on clearance and volume of distribution.

    The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.

  5. PK Parameter in Patients : Initial Elimination Half-life

    Time frame: Day 1 up to Day 7

    PK parameters were calculated using nonlinear 2-compartment population PK model with random patient effects on clearance and volume of distribution.

    The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.

  6. PK Parameter in Patients : Terminal Elimination Half-life

    Time frame: Day 1 up to Day 7

    PK parameters were calculated using nonlinear 2-compartment population PK model with random patient effects on clearance and volume of distribution.

    The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.

  7. Change From Baseline in C-reactive Protein (CRP)

    Time frame: Day 1 up to Day 7

    The change from Baseline in CRP levels were analysed and presented as per the planned time points.

    The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.

  8. Change From Baseline in Tumor Necrosis Factor (TNF)-Alpha

    Time frame: At Day 1, Day 2, Day 4, and Day 7

    The change from Baseline in TNF-alpha levels were analysed and presented as per the planned time points.

    The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.

  9. Change From Baseline in Interleukin-6 (IL-6)

    Time frame: At Day 1, Day 2, Day 4, and Day 7

    The change from Baseline in IL-6 levels were analysed and presented as per the planned time points.

    The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.

  10. Change From Baseline in Interleukin-10 (IL-10)

    Time frame: At Day 1, Day 2, Day 4, and Day 7

    The change from Baseline in IL-10 levels were analysed and presented as per the planned time points.

    The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.

  11. Change From Baseline in Interleukin-1 Receptor (IL-1R) Antagonist

    Time frame: At Day 1, Day 2, Day 4, and Day 7

    The change from Baseline in IL-1R levels were analysed and presented as per the planned time points.

    The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.

  12. Change From Baseline in Heart Rate

    Time frame: Day 1 up to Day 7

    The change from Baseline in heart rate was analysed and presented as per the planned time points.

    The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.

  13. Change From Baseline in Fluid Balance

    Time frame: Day 1 up to Day 7

    The change from Baseline in fluid balance were analysed and presented as per the planned time points. The fluid balance was adjusted for length of time interval and weight.

    The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.

  14. SOFA Score

    Time frame: Day 1 up to Day 7, Day 14 and Day 29

    The SOFA score, is used to track a patient's status during the stay in an intensive care unit. This scoring system is used to determine the extent of a person's organ function or rate of failure. The scoring system comprise of scores for six different system: Respiratory System; Nervous System; Cardiovascular System; Liver; Coagulation; and Renal System. Score for each system ranges from 0-4 (0=normal, 4=worst).

    Total SOFA score is a sum of the individual system score and range from 0 to 24, 0 being the better and 24 being the worst patient status.

    The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.

  15. Pulmonary Function : Change From Baseline in PaO2/FiO2

    Time frame: Day 1 up to Day 7

    Change from Baseline in PaO2/FiO2 was observed at each time-point.

    The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.

  16. Pulmonary Function : Change From Baseline in Tidal Volume

    Time frame: Day 1 up to Day 7

    Change from Baseline in tidal volume was observed at each time-point.

    The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.

  17. Change From Baseline in Arterial Blood Gas (Lactate)

    Time frame: Day 1 up to Day 7

    Change from Baseline in arterial blood gas (lactate) was observed at each time-point.

    The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.

  18. Days Alive and Free of Any Organ Dysfunction at Day 7

    Time frame: At Day 7

    Percentage of days alive and free of any organ dysfunction (i.e. no. of days divided by 7).

    The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.

  19. Percentage of Patients Alive and Free of All Vasopressors

    Time frame: At Day 7, Day 14 and Day 28

    Percentage of patients alive and free of all vasopressors was assessed on Days 7, 14, and 28.

    The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.

  20. Percentage of Days Alive and Free of Dialysis

    Time frame: At Day 7, Day 14 and Day 28

    Percentage of days alive and free of dialysis was assessed on Days 7, 14, and 28.

    The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.

  21. Percentage of Days Alive and Free of Ventilation

    Time frame: At Day 7

    Percentage of days alive and free of ventilation was assessed on Days 7, 14, and 28.

    The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.

  22. Mortality

    Time frame: At Day 1, 7, 14, and 28

    Mortality was assessed as percentage of patients dead at pre-specified time points.

    The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.

  23. Incidence of Abnormal Changes in ECG

    Time frame: Day 1 up to Day 7

    The number of patients having abnormal changes in ECG variables during the trial period was presented.

    The patients (n=2) in the FE 202158 3.75 ng/kg/min dose group were both discontinued within 5 hours after start of infusion. Therefore, no adequate data was available to perform the analysis for the outcome.

Sponsors and collaborators

Lead sponsor

Ferring Pharmaceuticals

Industry

Registry information

Official study title

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

Important dates

Study start
2009
Primary completion
2011
Study completion
2011
First posted
Oct 23, 2009
Registry last updated
Sep 25, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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