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Trial record 1 of 2 for:    Inotrem | Septic Shock
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Efficacy, Safety and Tolerability of Nangibotide in Patients With Septic Shock (ASTONISH)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT04055909
Recruitment Status : Active, not recruiting
First Posted : August 14, 2019
Last Update Posted : April 11, 2023
Information provided by (Responsible Party):

Brief Summary:
This is a randomized, double-blind, placebo-controlled dose-selection study in which two doses of nangibotide are tested versus placebo.

Condition or disease Intervention/treatment Phase
Shock, Septic Drug: nangibotide low dose Drug: nangibotide high dose Drug: placebo Phase 2

Detailed Description:

All patients with a diagnosis of septic shock will be considered for study participation. All potential study patients will receive standard of care for the treatment of septic shock.

After screening for eligibility, patients meeting all inclusion and no exclusion criterion will be randomized. Patients will be randomized to one of three treatment arms.

Treatment with study drug must be initiated as early as possible, but no later than 24 hours after the onset of septic shock, defined by the start of vasopressor therapy.

Patients will be treated for at least 3 days with study drug. After the first 3 days of treatment, patients still requiring vasopressor will be treated until 24 hours after vasopressor withdrawal with a maximum treatment duration of 5 days.

Patients will be assessed at the End of Study (EoS) visit at day 28. After the last patient's day 28 visit, the study will be analyzed. Additional follow up (FU) visits will be conducted after 90 days, 6 and 12 months.

The objective of the study ist to compare the safety, tolerability and efficacy of two doses of nangibotide versus placebo, when given in addition to standard of care.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 355 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Efficacy, Safety and Tolerability of Nangibotide in Patients With Septic Shock. A Randomized, Double-blind, Placebo Controlled Dose Selection Study
Actual Study Start Date : November 13, 2019
Actual Primary Completion Date : May 9, 2022
Estimated Study Completion Date : May 9, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Shock

Arm Intervention/treatment
Experimental: nangibotide 1
Treatment with study drug at at dose of 0.3mg/kg/hr
Drug: nangibotide low dose
nangibotide 0.3 mg/kg/h
Other Name: LR12

Experimental: nangibotide 2
Treatment with study drug at at dose of 1.0mg/kg/hr
Drug: nangibotide high dose
nangibotide 1.0 mg/kg/h
Other Name: LR12

Placebo Comparator: Placebo
Treatment with a matched placebo infusion
Drug: placebo
matching placebo
Other Name: matched placebo

Primary Outcome Measures :
  1. Sequential organ failure assessment (SOFA) score [ Time Frame: day 5 ]
    Change of total SOFA score from baseline to day 5 (in the subgroup defined by patients with elevated sTREM-1 baseline levels and in the overall population)

Secondary Outcome Measures :
  1. All-cause mortality [ Time Frame: day 5 and day 28 ]
    all-cause mortality on D5 and D28

  2. Duration of ICU stay [ Time Frame: day 28 ]

  3. Organe support free survival [ Time Frame: day 28 ]
    time to organe support free

  4. Sepsis support index (SSI) [ Time Frame: day 28 ]
    Sepsis support index

  5. Daily change of total Sequential organ failure assessment (SOFA) score and individual subscores [ Time Frame: day 1, day 2, day 3, day 4, day 5, day 6 and day 7 ]
    Daily change of total SOFA score and individual subscores

  6. Duration of Vasopressor use [ Time Frame: day 28 ]
    Change in the Duration of Vasopressor use

  7. Duration of Invasive mechanical ventilation (IMV) [ Time Frame: day 28 ]
    Change in the Duration of Invasive mechanical ventilation (IMV)

  8. Duration of Renal support [ Time Frame: day 28 ]
    Change in the Duration of renal replacement therapy, RRT

  9. All-cause mortality [ Time Frame: 12 months ]
    all-cause mortality up to 12 months

  10. Septic shock related mortality at day 28 [ Time Frame: day 28 ]
    mortality caused by septic shock

  11. Incidence of secondary infections and post shock antibiotic use [ Time Frame: day 28 ]
    Incidence of secondary infections and post shock antibiotic use

  12. Alive and organ support free at day 28 [ Time Frame: day 28 ]
    Proportion of patients alive and free of organ support at day 28

  13. Overall survival on day 28 [ Time Frame: day 28 ]
    time from the date of study drug start to date of death from any cause

  14. Overall survival up to 12 months [ Time Frame: 12 months ]
    Overall survival up to 12 months

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Provide written informed consent
  2. Age 18 to 85 years (inclusive)
  3. Documented or suspected infection: lung, abdominal or urinary tract infection (UTI) in the elderly (≥65 years)
  4. Organ dysfunction defined as acute change in total SOFA score ≥ 2 points
  5. Refractory hypotension requiring vasopressors to maintain MAP ≥65mm Hg despite adequate volume resuscitation
  6. Hyperlactatemia (blood lactate >2 mmol/L or 18 mg/dL).

Exclusion Criteria:

  1. Previous episode of septic shock requiring vasopressor administration within current hospital stay
  2. Underlying concurrent immunodepression with anti-CD52 alemtuzumab (Campath) or glucocorticoids >75 mg prednisone daily or equivalent for more than 7 days
  3. Immunosuppressive therapy related to recent (<6 months) transplantation
  4. Cancer chemotherapy (<3 months) implying an immunodepression
  5. Known HIV infection with low CD4 cell count (<200) for at least 6 months
  6. Known pregnancy (positive urine or serum pregnancy test)
  7. Shock of any other cause, e.g. hypotension related to gastrointestinal bleeding
  8. Ongoing documented or suspected endocarditis, history of prosthetic heart valves
  9. Prolonged QT syndrome
  10. End-stage neurological disease
  11. End-stage cirrhosis (Child Pugh Class C)
  12. Acute Physiology and Chronic Health Evaluation (APACHE II) score <15 or ≥ 34
  13. Home oxygen therapy on a regular basis for > 6 h/day
  14. Recent cardiopulmonary resuscitation (CPR) (within current hospital stay)
  15. Body mass index (BMI) ≥ 40 kg/m2or weight ≥ 130 kg
  16. Moribund patients
  17. Decision to limit full care taken before obtaining informed consent
  18. Participation in another interventional study in the 3 months prior to randomization

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04055909

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Sponsors and Collaborators
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Study Director: Jean-Jacques Garaud, MD CEO and Medical Officer
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Inotrem
ClinicalTrials.gov Identifier: NCT04055909    
Other Study ID Numbers: MOT-C-203
2018-004827-36 ( EudraCT Number )
First Posted: August 14, 2019    Key Record Dates
Last Update Posted: April 11, 2023
Last Verified: April 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Inotrem:
Septic Shock
Additional relevant MeSH terms:
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Shock, Septic
Pathologic Processes
Systemic Inflammatory Response Syndrome
Anti-Inflammatory Agents