Clinical Trial: Treatment of Patients With Early Septic Shock and Bio-Adrenomedullin(ADM) Concentration > 70 pg/ml With ADRECIZUMAB

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: A Double-Blind, Placebo-Controlled, Randomized, Multicenter, Proof of Concept and Dose-Finding Phase II Clinical Trial to Investigate the Safety, Tolerability and Efficacy of ADRECIZUMAB in Patients W

Brief Summary: This is a double-blind, placebo-controlled, randomized, multicenter proof of concept and dose-finding phase II study using two doses of ADRECIZUMAB in patients with early septic shock and a bio-ADM plasma concentration at admission of > 70 pg/ml.

Detailed Summary:

This is a double-blind, placebo-controlled, randomized, multicenter proof of concept and dose-finding phase II study using two doses of ADRECIZUMAB in patients with early septic shock and a bio-ADM plasma concentration at admission of > 70 pg/ml.

"Early" septic shock is defined as a life-threatening organ dysfunction due to dysregulated host response to a proven or suspected infection which leads to a decline of Mean Arterial Pressure (MAP) < 65 mmHg, which is refractory to fluid resuscitation and requires vasopressors. Early is defined as a maximum of less than 12 hours between onset of the cardiovascular organ-dysfunction and administration of ADRECIZUMAB. Refractoriness to fluid resuscitation is defined as a lack of response to the administration of 30 mL of fluid per kilogram of body weight or is determined according to a clinician's assessment of inadequate hemodynamic results.

It is intended to enroll 300 patients from surgical, medical and mixed ICU at multiple centers in Europe.

All patients will be treated according to "International Guidelines for Management of Severe Sepsis and Septic Shock".

Eligible patients (confirmed by central verification) will be randomized (1:1:2) to ADRECIZUMAB treatment arm A (2 mg/kg) or to ADRECIZUMAB treatment arm B (4 mg/kg) or to placebo as control group. Patients assigned to the treatment arm A or B will be administered a single dose of ADRECIZUMAB as intravenous infusion over approximately 1 hour; patients assigned to the control group will be administered placebo as intravenous infusion over approximately 1 hour.

As long as the patients are on the ICU, daily measurements of clinical signs and laboratory d
Sponsor: Adrenomed AG

Current Primary Outcome:

  • Endpoints for Primary Objective (Safety and Tolerability of Adrecizumab: Mortality) [ Time Frame: 90 days ]
    The endpoints for the primary objective are to determine over the 90 days study period: Mortality related to ADRECIZUMAB
  • Endpoints for Primary Objective (Safety and Tolerability of Adrecizumab: interruption of infusion) [ Time Frame: 90 days ]
    The endpoints for the primary objective are to determine over the 90 days study period: Interruption of infusion due to intolerability of ADRECIZUMAB
  • Endpoints for Primary Objective (Safety and Tolerability of Adrecizumab: new treatment emergent AEs) [ Time Frame: 90 days ]
    The endpoints for the primary objective are to determine over the 90 days study period: New treatment-emergent adverse events related to ADRECIZUMAB
  • Endpoints for Primary Objective (Safety and Tolerability of Adrecizumab: severity and frequency of AEs) [ Time Frame: 90 days ]
    The endpoints for the primary objective are to determine over the 90 days study period: Changes in severity and frequency of treatment-emergent adverse events


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Efficacy to be determined by Sepsis Support Index (SSI) [ Time Frame: 14 days ]
    The primary efficacy endpoint of this study is the Sepsis Support Index (SSI) defined as: days with organ support or dead within 14 day follow up More precisely: In the time frame of 14 day follow-up, each day on support with vasopressor, and/or mechanical ventilation, and/or renal dysfunction (defined as renal SOFA = 4), or not alive, is counted as 1. The sum over the follow up period is defined as SSI.
  • Sepsis Support Index (SSI) [ Time Frame: 28 days ]
    Sepsis Support Index (SSI) at 28 day follow-up
  • Penalized Sepsis Support Index (pSSI) at 14 and 28 day follow-up [ Time Frame: day 14 and day 28 ]
    Penalized Sepsis Support Index (pSSI) at 14 and 28 day follow-up, defined similar to the SSI with the exception that patients that die get penalized by assigning the maximum value, i.e. the pSSI is set to 14 or 28, respectively
  • Persistent organ dysfunction or death at 14 and 28 day follow-up [ Time Frame: day 14 and day 28 ]
    Persistent organ dysfunction or death at 14 and 28 day follow-up
  • Mortality Rate [ Time Frame: day 28 and day 90 ]
    Day 28 and day 90 mortality rate
  • SSI and pSSI excluding the renal component [ Time Frame: 90 days ]
    SSI and pSSI excluding the renal component
  • Individual Sepsis Support Index components [ Time Frame: 90 days ]
    Individual Sepsis Support Index components (hemodynamic, respiratory and renal failure) with and without mortality
  • Sequential Organ Failure Assessment (SOFA) Score : Composite measure: SOFA score and its changes over time [ Time Frame: 90 days ]

    Sequential Organ Failure Assessment (SOFA) Score:

    • Mean/maximum/total daily SOFA score during stay at ICU
    • Delta SOFA score, defined as maximum versus minimum SOFA during ICU stay
    • Change in SOFA score within 48 hours
    • SOFA-3 (score limited to cardiovascular, respiratory and renal function)
  • Improvement in renal function [ Time Frame: day 1, day 3 and day 7 ]
    Improvement in renal function as change in penKid and creatinine (day 3 - day 1, day 7 - day 1)
  • Length of stay at ICU/ hospital [ Time Frame: 90 days ]
    Length of stay at ICU/ hospital
  • Changes of functional parameter Mean Arterial Pressure during stay at ICU [ Time Frame: 90 days ]
    Changes of Mean Arterial Pressure (MAP)
  • Changes of functional parameter creatinine during stay at ICU [ Time Frame: 90 days ]
    Changes of creatinine
  • Changes of functional Parameter Partial Pressure of Oxygen in Arterial Blood(PaO2) / Fraction of inspired oxygen (FiO2) during stay at ICU [ Time Frame: 90 days ]
    Changes of PaO2/FiO2
  • Changes of functional Parameter blood lactate during stay at ICU [ Time Frame: 90 days ]
    Changes of blood lactate
  • Changes of functional Parameter fluid balance during stay at ICU [ Time Frame: 90 days ]
    Changes of fluid balance
  • Changes of functional Parameter Mid-Regional pro-Adrenomedullin (MR-proADM) during stay at ICU [ Time Frame: 90 days ]
    Changes of MR-proADM
  • Changes of functional parameter inflammatory marker Procalcitonine (PCT) during stay at ICU [ Time Frame: 90 days ]
    Changes of inflammatory marker PCT
  • Changes of functional Parameter inflammatory marker Interleukin-6 (IL-6) during stay at ICU [ Time Frame: 90 days ]
    Changes of inflammatory marker IL-6
  • Vasopressor use [ Time Frame: 90 days ]
    Vasopressor use (drug, highest/lowest dose, duration)
  • APACHE II score measurement [ Time Frame: 90 days ]
    APACHE II score measurement
  • Patient reported outcomes : Quality of Life by Euro-QoL-5 [ Time Frame: day 1, day 28 and day 90 ]
    Patient reported outcomes : Quality of Li

    Original Secondary Outcome: Same as current

    Information By: Adrenomed AG

    Dates:
    Date Received: February 22, 2017
    Date Started: May 2017
    Date Completion: March 2019
    Last Updated: March 15, 2017
    Last Verified: March 2017