Volume Therapy With Crystalloids and Colloids and Hemodynamic Monitoring in Patients With Severe Sepsis

NCT02587078 | Withdrawn Phase 4

• 2 other identifiers: 12-VS01-012012-000331-30
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The primary alternative hypothesis is that less time (minutes) is required, to achieve the initial hemodynamic stabilization, with Volulyte® compared to Jonosteril®.

• H01: Minutes with Volulyte® ≥ Minutes with Jonosteril®
• H11: Minutes with Volulyte® \< Minutes with Jonosteril®

Conditions

Severe Sepsis

Keywords

Haemodynamic stabilization

Outcome Measures

Primary Outcomes (1)

• The primary endpoint is defined as the fraction of patients who achieved initial hemodynamic stabilization during the first 6 hours after randomisation.

  During the first 6 hours

Secondary Outcomes (1)

• Time needed for achievement of initial hemodynamic stabilization during the first 24 hours after randomization.

  during the first 24 hours after randomization.

Study Arms (2)

Volulyte

ACTIVE COMPARATOR

Patients who meet the inclusion criteria (at Screening, see below for definition) will be randomized immediately in a ratio of 1:1 to either intravenous Volulyte® or Jonosteril® for fluid resuscitation (on RAND). Fluid resuscitation with study drug will be started immediately in order to reach initial hemodynamic stabilization.

Drug: Jonosteril

Jonosteril

ACTIVE COMPARATOR

Patients who meet the inclusion criteria (at Screening, see below for definition) will be randomized immediately in a ratio of 1:1 to either intravenous Volulyte® or Jonosteril® for fluid resuscitation (on RAND). Fluid resuscitation with study drug will be started immediately in order to reach initial hemodynamic stabilization.

Drug: Volulyte

Interventions

Volulyte DRUG

Patients who meet the inclusion criteria (at Screening, see below for definition) will be randomized immediately in a ratio of 1:1 to either intravenous Volulyte® or Jonosteril® for fluid resuscitation (on RAND). Fluid resuscitation with study drug will be started immediately in order to reach initial hemodynamic stabilization.

Jonosteril

Jonosteril DRUG

Patients who meet the inclusion criteria (at Screening, see below for definition) will be randomized immediately in a ratio of 1:1 to either intravenous Volulyte® or Jonosteril® for fluid resuscitation (on RAND). Fluid resuscitation with study drug will be started immediately in order to reach initial hemodynamic stabilization.

Volulyte

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patient aged 18 years or older
• Presence of severe sepsis defined as:
• Sepsis due to a known or suspected infection with two or more of the modified systemic inflammatory response syndrome (SIRS) criteria (46).
• Temperature (\> 38°C or \< 36°C)
• Heart rate (\> 90 beats / minute)
• Respiratory rate (\>20 breaths / minute) or arterial carbon dioxide (PaCO2) \< 32 mmHg (\< 4.3 kPa)
• White blood cells (WBC) \> 12.000 cells/mm3, \< 4000 cells/mm3, or \> 10% immature (band) forms
• Severe sepsis for less than 24 hours with at least one of the following characteristics:
• Ratio of partial pressure of oxygen to the fraction of inspired oxygen (PaO2/FiO2) \< 250
• Arterial pH \< 7.3 or serum lactate level \> 1.5 × ULN (upper limit of normal)
• Hypotension: Inadequately fluid resuscitated patients with a systolic blood pressure ≤ 90 mmHg or MAP ≤ 70 mmHg, or adequately fluid resuscitated patients requiring vasopressors to maintain blood pressure within normal ranges
• Urine output \< 0.5 ml/kg/hour (patients who are inadequately fluid resuscitated)
• Platelet count \< 80.000/ mm3
• Acute alteration of mental status
• Requirement for fluid resuscitation as defined by the measured hemodynamic parameters MAP, ScvO2 and PPV or PLR.

You may not qualify if:

• Participation in another clinical study with an investigational drug or an investigational medical device within 30 days before screening or planned during the study period.
• Known hypersensitivity to any components of the investigated solutions.
• Known pregnancy; female patients must be surgically sterile; or postmenopausal for at least two years; or if of childbearing potential must have a negative serum or urine dipstick pregnancy test (if a test result is not available at the time of randomization, a patient may be randomized and treated initially, however, has to be withdrawn immediately from the study as soon as the test result becomes available and is positive).
• Known serum creatinine \> 300 μmol/L, corresponding to 3.4 mg/dL (if a serum creatinine value is not available at the time of randomization or an available value is older than 24 hours, a patient may be randomized and treated. If a creatinine value of \> 300 μmol/L becomes available later, treatment with the study drug may be continued if the risk/benefit ratio for the individual patient is regarded as positive by the investigator.)
• Known history of chronic renal failure (hemodialysis)
• Anuria lasting more than 8 hours (\<50ml urine output / 8 hours) despite fluid resuscitation prior to randomization.
• Requirement for renal support (either continuous or discontinuous techniques, including intermittent hemodialysis, hemofiltration and hemodiafiltration)
• History of known hemostatic disorders with clinical bleeding (hemophilia and known or suspected Willebrand disease)
• Burns \>20% of body surface
• State of brain death
• Known co-morbidities: Hematologic malignant disorders, neutropenia (polymorphonuclear leukocytes \[PMN\] \< 500/mm3), proven liver cirrhosis, Aquired immunodeficiency syndrome (AIDS) Expected requirement for concomitant cancer therapy (e.g. chemotherapradiotherapy or surgery) from randomization until Day 4 Requirement for concomitant cancer therapy (e.g. chemotherapy, radiotherapy or surgery) from randomization until Day 4
• Known fluid overload (EVLWI \> 10 ml/kg BW)
• Need for fluid restriction
• Refractory septic shock defined as severe sepsis with hypotension unresponsive to adequate fluid resuscitation, along with the presence of hypoperfusion abnormalities or organ dysfunction as defined by Bone et al., 1992. Patients receiving inotropic or vasopressor agents may no longer be hypotensive by the time they manifest hypoperfusion abnormalities or organ dysfunction, yet they would still be considered to have septic shock. Patients treated with low dose vasopressors are not excluded provided they are responsive to fluid resuscitation as demonstrated by an individual fluid challenge. Patients receiving norepinephrine (noradrenaline) or epinephrine (adrenaline) at a dose \> 0.5 μg/kg/min or dopamine at a dose \> 15 μg/kg/min at the timepoint of Screening are not eligible for the study.
• Intracranial bleeding

Sponsors & Collaborators

• Wuerzburg University Hospital: lead

MeSH Terms

Conditions

Sepsis

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 10, 2014
• First Posted: October 27, 2015
• Study Start: March 1, 2013
• Primary Completion: June 1, 2013
• Study Completion: June 1, 2013
• Last Updated: November 30, 2016

Record last verified: 2016-03