- ICH GCP
- Register voor klinische proeven in de VS.
- Klinische proef NCT01000649
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
Studie Overzicht
Toestand
Conditie
Interventie / Behandeling
Gedetailleerde beschrijving
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.
Studietype
Inschrijving (Werkelijk)
Fase
- Fase 2
Contacten en locaties
Studie Locaties
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Brussels, België
- Clinique Universitaire St-Luc
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Brussels, België
- Erasme Hospital (Free University of Brussels)
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Brussels, België
- University Hospital Vrije Universiteit
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Dinant, België
- Service des Soins Intensits
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Vancouver, Canada
- Royal Columbian Hospital
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Vancouver, Canada
- St. Paul´s Hospital
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Bispebjerg, Denemarken
- Bispebjerg Hospital
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Copenhagen, Denemarken
- Rigshospitalet
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Hillerød, Denemarken
- Hillerød Hospital
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Hvidovre, Denemarken
- Hvidovre Hospital
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Delaware
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Newark, Delaware, Verenigde Staten
- Christiana Care Health System
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Massachusetts
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Springfield, Massachusetts, Verenigde Staten
- Baystate Medical Center
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Minnesota
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Duluth, Minnesota, Verenigde Staten
- Division of Education and Research SMDC Health System
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New Jersey
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Camden, New Jersey, Verenigde Staten
- Cooper University Hospital
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New York
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New York, New York, Verenigde Staten
- Mount Sinai School of Medicine
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Texas
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Houston, Texas, Verenigde Staten
- Baylor College of Medicine
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Deelname Criteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
Accepteert gezonde vrijwilligers
Geslachten die in aanmerking komen voor studie
Beschrijving
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
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: Gerandomiseerd
- Interventioneel model: Parallelle opdracht
- Masker: Verdrievoudigen
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
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Experimenteel: 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. |
FE 202158 at dose 1.25 ng/kg/min infused.
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Experimenteel: 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. |
FE 202158 at dose 2.5 ng/kg/min infused.
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Experimenteel: 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. |
FE 202158 at dose 3.75 ng/kg/min infused.
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Placebo-vergelijker: PLCBO
Patients in the arm received an intravenous infusion for up to 7 days of placebo.
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Isotonic saline infused.
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Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
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Proportion of Patients Maintaining Target Mean Arterial Pressure (MAP) (>60 mmHg) With no Open Label NE (Norepinephrine)
Tijdsspanne: Day 1 up to Day 7
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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. |
Day 1 up to Day 7
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Proportion of Patients Maintaining Target MAP (>60) Irrespective of Open Label NE
Tijdsspanne: Day 1 up to Day 7
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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. |
Day 1 up to Day 7
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Cumulative Dose of Open Label NE.
Tijdsspanne: Day 1 up to Day 7
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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. |
Day 1 up to Day 7
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Infusion Rates of Open Label NE.
Tijdsspanne: Day 1 up to Day 7
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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. |
Day 1 up to Day 7
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Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
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Pharmacokinetic (PK) Parameter in Patients : Steady State Concentration
Tijdsspanne: Day 1 up to Day 7
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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. |
Day 1 up to Day 7
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PK Parameter in Patients : Time to Steady State
Tijdsspanne: Day 1 up to Day 7
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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. |
Day 1 up to Day 7
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PK Parameter in Patients : Clearance
Tijdsspanne: Day 1 up to Day 7
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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. |
Day 1 up to Day 7
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PK Parameter in Patients : Steady State Volume of Distribution
Tijdsspanne: Day 1 up to Day 7
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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. |
Day 1 up to Day 7
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PK Parameter in Patients : Initial Elimination Half-life
Tijdsspanne: Day 1 up to Day 7
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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. |
Day 1 up to Day 7
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PK Parameter in Patients : Terminal Elimination Half-life
Tijdsspanne: Day 1 up to Day 7
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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. |
Day 1 up to Day 7
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Change From Baseline in C-reactive Protein (CRP)
Tijdsspanne: Day 1 up to Day 7
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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. |
Day 1 up to Day 7
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Change From Baseline in Tumor Necrosis Factor (TNF)-Alpha
Tijdsspanne: At Day 1, Day 2, Day 4, and Day 7
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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. |
At Day 1, Day 2, Day 4, and Day 7
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Change From Baseline in Interleukin-6 (IL-6)
Tijdsspanne: At Day 1, Day 2, Day 4, and Day 7
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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. |
At Day 1, Day 2, Day 4, and Day 7
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Change From Baseline in Interleukin-10 (IL-10)
Tijdsspanne: At Day 1, Day 2, Day 4, and Day 7
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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. |
At Day 1, Day 2, Day 4, and Day 7
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Change From Baseline in Interleukin-1 Receptor (IL-1R) Antagonist
Tijdsspanne: At Day 1, Day 2, Day 4, and Day 7
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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. |
At Day 1, Day 2, Day 4, and Day 7
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Change From Baseline in Heart Rate
Tijdsspanne: Day 1 up to Day 7
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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. |
Day 1 up to Day 7
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Change From Baseline in Fluid Balance
Tijdsspanne: Day 1 up to Day 7
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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. |
Day 1 up to Day 7
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SOFA Score
Tijdsspanne: Day 1 up to Day 7, Day 14 and Day 29
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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. |
Day 1 up to Day 7, Day 14 and Day 29
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Pulmonary Function : Change From Baseline in PaO2/FiO2
Tijdsspanne: Day 1 up to Day 7
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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. |
Day 1 up to Day 7
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Pulmonary Function : Change From Baseline in Tidal Volume
Tijdsspanne: Day 1 up to Day 7
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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. |
Day 1 up to Day 7
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Change From Baseline in Arterial Blood Gas (Lactate)
Tijdsspanne: Day 1 up to Day 7
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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. |
Day 1 up to Day 7
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Days Alive and Free of Any Organ Dysfunction at Day 7
Tijdsspanne: At Day 7
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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. |
At Day 7
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Percentage of Patients Alive and Free of All Vasopressors
Tijdsspanne: At Day 7, Day 14 and Day 28
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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. |
At Day 7, Day 14 and Day 28
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Percentage of Days Alive and Free of Dialysis
Tijdsspanne: At Day 7, Day 14 and Day 28
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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. |
At Day 7, Day 14 and Day 28
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Percentage of Days Alive and Free of Ventilation
Tijdsspanne: At Day 7
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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. |
At Day 7
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Mortality
Tijdsspanne: At Day 1, 7, 14, and 28
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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. |
At Day 1, 7, 14, and 28
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Incidence of Abnormal Changes in ECG
Tijdsspanne: Day 1 up to Day 7
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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. |
Day 1 up to Day 7
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Medewerkers en onderzoekers
Sponsor
Publicaties en nuttige links
Algemene publicaties
- 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.
- 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.
Studie record data
Bestudeer belangrijke data
Studie start
Primaire voltooiing (Werkelijk)
Studie voltooiing (Werkelijk)
Studieregistratiedata
Eerst ingediend
Eerst ingediend dat voldeed aan de QC-criteria
Eerst geplaatst (Schatting)
Updates van studierecords
Laatste update geplaatst (Werkelijk)
Laatste update ingediend die voldeed aan QC-criteria
Laatst geverifieerd
Meer informatie
Termen gerelateerd aan deze studie
Trefwoorden
Aanvullende relevante MeSH-voorwaarden
Andere studie-ID-nummers
- FE 202158 CS02
- EudraCT: 2009-010798-19
Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .
Klinische onderzoeken op Septische shock
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Haukeland University HospitalMinistry of Defence, NorwayVoltooidHemorragische shock | Hypovolemische shockNoorwegen
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King's College Hospital NHS TrustUniversity Hospital BirminghamVoltooidTraumatische hemorragische shockVerenigd Koninkrijk
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Massachusetts General HospitalBeth Israel Deaconess Medical Center; Boston Medical Center; Tufts Medical Center; Lahey Clinic en andere medewerkersWerving
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Jason SperryNational Heart, Lung, and Blood Institute (NHLBI)BeëindigdHemorragische shockVerenigde Staten
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University of Texas Southwestern Medical CenterUniversity of Washington; Resuscitation Outcomes ConsortiumVoltooidHemorragische shockVerenigde Staten
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Assiut UniversityOnbekend
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Centre Hospitalier Universitaire, AmiensIngetrokkenVaricesbloeding | Hemorragische shockFrankrijk
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Assistance Publique - Hôpitaux de ParisWervingSepsis | Schok | Hemorragische shockFrankrijk
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Isfahan University of Medical SciencesVoltooidHemorragische shock | IVC-inklapbaarheidsindexIran, Islamitische Republiek
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University of PennsylvaniaVoltooidCardiovasculaire shock | Circulatoire shockVerenigde Staten
Klinische onderzoeken op FE 202158 1.25
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Changchun Intellicrown Pharmaceutical Co. LTDWervingNiet-alcoholische steatohepatitis (NASH)China
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Swiss Federal Institute of TechnologyUnited States Agency for International Development (USAID); Quadram Institute... en andere medewerkersVoltooidIjzertekort | Bloedarmoede door ijzertekort | IJzertekort (zonder bloedarmoede)Peru
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GlyPharma TherapeuticsVectivBio AGIngetrokkenLymfoom, non-Hodgkin, volwassen | Lymfoom, Hodgkin, volwassen
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Ferring PharmaceuticalsVoltooidProstaatkankerVerenigd Koninkrijk
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Ferring PharmaceuticalsVoltooidHyperfagie bij het Prader-Willi-syndroomVerenigde Staten
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Swiss Federal Institute of TechnologyUniversity of MalawiVoltooidIJzer biologische beschikbaarheid van bioverrijkte zoete aardappel met oranje vruchtvlees (SASHA-II)Ijzertekort | Bloedarmoede door ijzertekortMalawi, Zwitserland
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Ferring PharmaceuticalsBeëindigd
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Ferring PharmaceuticalsVoltooidLuteale hormoonsupplementenJapan
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Swiss Federal Institute of TechnologyVoltooidMalaria, Falciparum | Haakworminfecties | Schistosoma HaematobiumIvoorkust
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IRCCS San RaffaeleVoltooid