Phase 2
Completed N=52
Effects of the V1a Agonist FE 202158 in Patients With Septic Shock
Source: ClinicalTrials.gov NCT01000649 ↗Enrolled (actual)
52
Serious AEs
23.1%
Results posted
Jun 2017
Primary outcomePrimary: Proportion of Patients Maintaining Target Mean Arterial Pressure (MAP) (>60 mmHg) With no Open Label NE (Norepinephrine) — 0.0; 47.1; 0.0; 10.0 Percentage of patients
Summary
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Proportion of Patients Maintaining Target Mean Arterial Pressure (MAP) (>60 mmHg) With no Open Label NE (Norepinephrine) |
0.0; 47.1; 0.0; 10.0; 68.8; 20.0 | — |
| PRIMARY Proportion of Patients Maintaining Target MAP (>60) Irrespective of Open Label NE |
100.0; 100.0; 94.7; 87.5; 100.0; 100.0 | — |
| PRIMARY Cumulative Dose of Open Label NE. |
14.3; 13.1; 19.2; 40.5; 30; 57.2 | — |
| PRIMARY Infusion Rates of Open Label NE. |
0.24; 0.22; 0.32; 0.22; 0.11; 0.31 | — |
| SECONDARY Pharmacokinetic (PK) Parameter in Patients : Steady State Concentration |
0.50; 0.99 | — |
| SECONDARY PK Parameter in Patients : Time to Steady State |
7.6; 7.0 | — |
| SECONDARY PK Parameter in Patients : Clearance |
10.0; 13.1 | — |
| SECONDARY PK Parameter in Patients : Steady State Volume of Distribution |
25.5; 31.2 | — |
| SECONDARY PK Parameter in Patients : Initial Elimination Half-life |
0.18; 0.17 | — |
| SECONDARY PK Parameter in Patients : Terminal Elimination Half-life |
2.5; 2.7 | — |
| SECONDARY Change From Baseline in C-reactive Protein (CRP) |
9.81; -4.84; 32.7; -16.2; -52.4; -5.63 | — |
| SECONDARY Change From Baseline in Tumor Necrosis Factor (TNF)-Alpha |
-0.75; -0.194; -0.125; -0.75; 0.0; 0.0 | — |
| SECONDARY Change From Baseline in Interleukin-6 (IL-6) |
-329; -524; -529; -720; -888; -398 | — |
| SECONDARY Change From Baseline in Interleukin-10 (IL-10) |
-19.2; -58.3; -25.8; -34; -78.9; -43 | — |
| SECONDARY Change From Baseline in Interleukin-1 Receptor (IL-1R) Antagonist |
0.763; -3.71; -3.28; -3.65; -4.77; -3.84 | — |
| SECONDARY Change From Baseline in Heart Rate |
-5.7; -11.0; -4.9; -4.9; -11.9; -6.55 | — |
| SECONDARY Change From Baseline in Fluid Balance |
-2.11; -0.0513; -0.477; -3.56; -0.889; -0.578 | — |
| SECONDARY SOFA Score |
8.7; 11.9; 10.5; 8.0; 8.68; 9.0 | — |
| SECONDARY Pulmonary Function : Change From Baseline in PaO2/FiO2 |
-1.7; 1.35; -7.06; 22.8; -11.9; 7.32 | — |
| SECONDARY Pulmonary Function : Change From Baseline in Tidal Volume |
-0.533; 0.196; -0.0189; -0.208; 0.256; -0.24 | — |
| SECONDARY Change From Baseline in Arterial Blood Gas (Lactate) |
0; -0.367; -0.0278; -0.489; -0.833; -0.0444 | — |
| SECONDARY Days Alive and Free of Any Organ Dysfunction at Day 7 |
5.38; 3.8; 0.0 | — |
| SECONDARY Percentage of Patients Alive and Free of All Vasopressors |
60.0; 57.9; 73.7; 40.0; 89.5; 94.7 | — |
| SECONDARY Percentage of Days Alive and Free of Dialysis |
53.9; 79.7; 83.2; 55.1; 80.1; 87.6 | — |
| SECONDARY Percentage of Days Alive and Free of Ventilation |
31.3; 53.8; 23.1 | — |
| SECONDARY Mortality |
0.0; 0.0; 0.0; 20.0; 0.0; 0.0 | — |
| SECONDARY Incidence of Abnormal Changes in ECG |
0; 1; 4; 5; 11; 8 | — |
Eligibility Criteria
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
Data sourced from ClinicalTrials.gov (NCT01000649). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.