Efficacy, Safety and Tolerability of Nangibotide in Patients With Septic Shock (ASTONISH)

April 7, 2023 updated by: Inotrem

Efficacy, Safety and Tolerability of Nangibotide in Patients With Septic Shock. A Randomized, Double-blind, Placebo Controlled Dose Selection Study

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

Study Overview

Status

Active, not recruiting

Conditions

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.

Study Type

Interventional

Enrollment (Actual)

355

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Bruxelles, Belgium
        • Cliniques Universitaires Saint-Luc
      • Genk, Belgium, 3600
        • Ziekenhuis Oost-Limburg
      • Gent, Belgium, 9000
        • UZ Gent
      • La Louvière, Belgium, 7100
        • Centre Hospitalier Jolimont-Lobbes
      • Lodelinsart, Belgium, 6042
        • CHU Marie Curie
      • Ottignies, Belgium, 1340
        • Clinique Saint-Pierre
      • Yvoir, Belgium, 5530
        • CHU UCL Namur asbl
      • Hillerod, Denmark, DK-3400
        • Nordsjællandshospital Hillerød
      • Helsinki, Finland, PL 340
        • Helsinki University Hospital Adult ICU PPDS
      • Kuopio, Finland, PO BOX 1777
        • Kuopion Yliopistollinen Sairaala
      • Tampere, Finland, PL 2000
        • Tampereen yliopistollinen sairaala
      • Angers, France, 49933
        • CHU Angers
      • Argenteuil, France, 95100
        • Centre Hospitalier Victor Dupouy
      • Bourg-en-Bresse, France, 01000
        • Hôpital Fleyriat
      • Béthune, France, 62408
        • Centre Hospitalier de Béthune
      • Dijon, France, 21079
        • Chu Dijon - Hôpital François Mitterrand
      • La Roche sur Yon, France, 85925
        • CHD Les Oudairies
      • Le Kremlin Bicêtre, France, 94270
        • Hopital de Bicetre
      • Le Mans, France, 72000
        • CHU Le Mans
      • Lille, France, 59037
        • CHRU Lille - Hôpital Roger Salengro
      • Limoges, France
        • Hôpital Universitaire Dupuytren
      • Lyon, France, 69495
        • Centre Hospitalier Lyon Sud
      • Marseille, France, 13015
        • Hopital Nord
      • Melun, France, 77000
        • Centre Hospitalier de Melun
      • Nancy, France, 54035
        • CHRU Nancy - Hôpital central
      • Nantes, France, 44093
        • Hôtel Dieu - Nanates
      • Nîmes, France, 30029
        • CHU de Nîmes
      • Orléans, France, 45067
        • Hôpital de la Source
      • Paris, France, 75010
        • Hôpital Saint Louis
      • Paris, France, 75010
        • Hopital Lariboisiere
      • Paris, France, 75014
        • Hôpital Cochin
      • Paris, France, 75013
        • Groupe Hospitalier Pitie-Salpetriere
      • Tours, France, 37044
        • CHRU Hôpital Bretonneau
      • Villenave d'Ornon, France, 33882
        • Hôpital d'Instruction des Armées Robert Picqué
      • Dublin, Ireland
        • St Jame's Hospital
      • Galway, Ireland, H91 YR71
        • Galway University Hospital
      • Barcelona, Spain
        • Hospital Universitario Vall d'Hebron
      • Barcelone, Spain, 08003
        • Hospital del Mar
      • Madrid, Spain, 28040
        • Hospital Clinical San Carlos
      • Oviedo, Spain, 33011
        • Hospital Universitario Dentral de Asturias
      • Terrassa, Spain, 08221
        • Hospital Universitari Mútua de Terrassa
      • Valencia, Spain, 46026
        • Hospital Universitario y Politécnico La Fe
      • Valencia, Spain, 46017
        • Hospital Universitario Dr. Peset Aleixandre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: nangibotide 1
Treatment with study drug at at dose of 0.3mg/kg/hr
nangibotide 0.3 mg/kg/h
Other Names:
  • LR12
Experimental: nangibotide 2
Treatment with study drug at at dose of 1.0mg/kg/hr
nangibotide 1.0 mg/kg/h
Other Names:
  • LR12
Placebo Comparator: Placebo
Treatment with a matched placebo infusion
matching placebo
Other Names:
  • matched placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)
day 5

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
All-cause mortality
Time Frame: day 5 and day 28
all-cause mortality on D5 and D28
day 5 and day 28
Duration of ICU stay
Time Frame: day 28
hospitalization
day 28
Organe support free survival
Time Frame: day 28
time to organe support free
day 28
Sepsis support index (SSI)
Time Frame: day 28
Sepsis support index
day 28
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
day 1, day 2, day 3, day 4, day 5, day 6 and day 7
Duration of Vasopressor use
Time Frame: day 28
Change in the Duration of Vasopressor use
day 28
Duration of Invasive mechanical ventilation (IMV)
Time Frame: day 28
Change in the Duration of Invasive mechanical ventilation (IMV)
day 28
Duration of Renal support
Time Frame: day 28
Change in the Duration of renal replacement therapy, RRT
day 28
All-cause mortality
Time Frame: 12 months
all-cause mortality up to 12 months
12 months
Septic shock related mortality at day 28
Time Frame: day 28
mortality caused by septic shock
day 28
Incidence of secondary infections and post shock antibiotic use
Time Frame: day 28
Incidence of secondary infections and post shock antibiotic use
day 28
Alive and organ support free at day 28
Time Frame: day 28
Proportion of patients alive and free of organ support at day 28
day 28
Overall survival on day 28
Time Frame: day 28
time from the date of study drug start to date of death from any cause
day 28
Overall survival up to 12 months
Time Frame: 12 months
Overall survival up to 12 months
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Investigators

  • Study Director: Jean-Jacques Garaud, MD, CEO and Medical Officer

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 13, 2019

Primary Completion (Actual)

May 9, 2022

Study Completion (Anticipated)

May 9, 2023

Study Registration Dates

First Submitted

August 12, 2019

First Submitted That Met QC Criteria

August 12, 2019

First Posted (Actual)

August 14, 2019

Study Record Updates

Last Update Posted (Actual)

April 11, 2023

Last Update Submitted That Met QC Criteria

April 7, 2023

Last Verified

April 1, 2023

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • MOT-C-203
  • 2018-004827-36 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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