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

Sponsor
Inotrem (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04055909
Collaborator
(none)
450
Enrollment
43
Locations
3
Arms
29.6
Anticipated Duration (Months)
10.5
Patients Per Site
0.4
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: nangibotide low dose
  • Drug: nangibotide high dose
  • Drug: placebo
 Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
450 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 :
Nov 13, 2019
Anticipated Primary Completion Date :
Apr 1, 2022
Anticipated Study Completion Date :
May 1, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: nangibotide 1

Drug: nangibotide low dose
nangibotide 0.3 mg/kg/h
Experimental: nangibotide 2

Drug: nangibotide high dose
nangibotide 1.0 mg/kg/h
Placebo Comparator: Placebo

Drug: placebo
matching placebo

Outcome Measures

Primary Outcome Measures

  1. Sequential organ failure assessment (SOFA) score [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 [day 28]

    Survival and all-cause mortality on D28

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 85 Years
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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Cliniques Universitaires Saint-Luc Bruxelles Belgium
2 Ziekenhuis Oost-Limburg Genk Belgium 3600
3 UZ Gent Gent Belgium 9000
4 Centre hospitalier Jolimont-Lobbes La Louvière Belgium 7100
5 CHU Marie Curie Lodelinsart Belgium 6042
6 Clinique Saint-Pierre Ottignies Belgium 1340
7 CHU UCL Namur asbl Yvoir Belgium 5530
8 Nordsjællandshospital Hillerød Hillerod Denmark DK-3400
9 Helsinki University Hospital Adult ICU PPDS Helsinki Finland PL 340
10 Kuopion Yliopistollinen sairaala Kuopio Finland PO BOX 1777
11 Tampereen yliopistollinen sairaala Tampere Finland PL 2000
12 CHU Angers Angers France 49933
13 Centre hospitalier Victor Dupouy Argenteuil France 95100
14 Hôpital Fleyriat Bourg-en-Bresse France 01000
15 Centre hospitalier de Béthune Béthune France 62408
16 CHU Dijon - Hôpital François Mitterrand Dijon France 21079
17 CHD les Oudairies La Roche sur Yon France 85925
18 Hôpital de Bicêtre Le Kremlin Bicêtre France 94270
19 CHU LE Mans Le Mans France 72000
20 CHRU Lille - Hôpital Roger Salengro Lille France 59037
21 Hôpital Universitaire Dupuytren Limoges France
22 Centre Hospitalier Lyon Sud Lyon France 69495
23 Hôpital Nord Marseille France 13015
24 Centre hospitalier de Melun Melun France 77000
25 CHRU Nancy - Hôpital Central Nancy France 54035
26 Hôtel Dieu - Nanates Nantes France 44093
27 CHU de Nîmes Nîmes France 30029
28 Hôpital de la source Orléans France 45067
29 Hôpital Lariboisière Paris France 75010
30 Hôpital Saint Louis Paris France 75010
31 Groupe hospitalier Pitié-Salpêtrière Paris France 75013
32 Hôpital Cochin Paris France 75014
33 CHRU Hôpital Bretonneau Tours France 37044
34 Hôpital d'instruction des Armées Robert Picqué Villenave d'Ornon France 33882
35 St Jame's Hospital Dublin Ireland
36 Galway University Hospital Galway Ireland H91 YR71
37 Hospital Universitario Vall d'Hebrón Barcelona Spain
38 Hospital del mar Barcelone Spain 08003
39 Hospital Clinical San Carlos Madrid Spain 28040
40 Hospital Universitario Dentral de Asturias Oviedo Spain 33011
41 Hospital Universitari Mutua de Terrassa Terrassa Spain 08221
42 Hospital universitario DR. Peset Aleixandre Valencia Spain 46017
43 Hospital Universitario y Politecnico la Fe Valencia Spain 46026

Sponsors and Collaborators

  • Inotrem

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Inotrem
ClinicalTrials.gov Identifier:
NCT04055909
Other Study ID Numbers:
  • MOT-C-203
  • 2018-004827-36
First Posted:
Aug 14, 2019
Last Update Posted:
Apr 1, 2022
Last Verified:
Jun 1, 2021
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
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:
Shock, Septic
Shock
Nangibotide

Study Results

No Results Posted as of Apr 1, 2022