Efficacy, Safety and Tolerability of Nangibotide in Patients With Septic Shock (ASTONISH)
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| ClinicalTrials.gov Identifier: NCT04055909 |
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Recruitment Status :
Active, not recruiting
First Posted : August 14, 2019
Last Update Posted : April 11, 2023
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Shock, Septic | Drug: nangibotide low dose Drug: nangibotide high dose Drug: placebo | Phase 2 |
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 (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 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: nangibotide 1
Treatment with study drug at at dose of 0.3mg/kg/hr
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Drug: nangibotide low dose
nangibotide 0.3 mg/kg/h
Other Name: LR12 |
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Experimental: nangibotide 2
Treatment with study drug at at dose of 1.0mg/kg/hr
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Drug: nangibotide high dose
nangibotide 1.0 mg/kg/h
Other Name: LR12 |
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Placebo Comparator: Placebo
Treatment with a matched placebo infusion
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Drug: placebo
matching placebo
Other Name: matched placebo |
- 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)
- All-cause mortality [ Time Frame: day 5 and day 28 ]all-cause mortality on D5 and D28
- Duration of ICU stay [ Time Frame: day 28 ]hospitalization
- Organe support free survival [ Time Frame: day 28 ]time to organe support free
- Sepsis support index (SSI) [ Time Frame: day 28 ]Sepsis support index
- 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
- Duration of Vasopressor use [ Time Frame: day 28 ]Change in the Duration of Vasopressor use
- Duration of Invasive mechanical ventilation (IMV) [ Time Frame: day 28 ]Change in the Duration of Invasive mechanical ventilation (IMV)
- Duration of Renal support [ Time Frame: day 28 ]Change in the Duration of renal replacement therapy, RRT
- All-cause mortality [ Time Frame: 12 months ]all-cause mortality up to 12 months
- Septic shock related mortality at day 28 [ Time Frame: day 28 ]mortality caused by septic shock
- Incidence of secondary infections and post shock antibiotic use [ Time Frame: day 28 ]Incidence of secondary infections and post shock antibiotic use
- Alive and organ support free at day 28 [ Time Frame: day 28 ]Proportion of patients alive and free of organ support at 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
- Overall survival up to 12 months [ Time Frame: 12 months ]Overall survival up to 12 months
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.
| Ages Eligible for Study: | 18 Years to 85 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Provide written informed consent
- Age 18 to 85 years (inclusive)
- Documented or suspected infection: lung, abdominal or urinary tract infection (UTI) in the elderly (≥65 years)
- Organ dysfunction defined as acute change in total SOFA score ≥ 2 points
- Refractory hypotension requiring vasopressors to maintain MAP ≥65mm Hg despite adequate volume resuscitation
- Hyperlactatemia (blood lactate >2 mmol/L or 18 mg/dL).
Exclusion Criteria:
- Previous episode of septic shock requiring vasopressor administration within current hospital stay
- Underlying concurrent immunodepression with anti-CD52 alemtuzumab (Campath) or glucocorticoids >75 mg prednisone daily or equivalent for more than 7 days
- Immunosuppressive therapy related to recent (<6 months) transplantation
- Cancer chemotherapy (<3 months) implying an immunodepression
- Known HIV infection with low CD4 cell count (<200) for at least 6 months
- Known pregnancy (positive urine or serum pregnancy test)
- Shock of any other cause, e.g. hypotension related to gastrointestinal bleeding
- Ongoing documented or suspected endocarditis, history of prosthetic heart valves
- Prolonged QT syndrome
- End-stage neurological disease
- End-stage cirrhosis (Child Pugh Class C)
- Acute Physiology and Chronic Health Evaluation (APACHE II) score <15 or ≥ 34
- Home oxygen therapy on a regular basis for > 6 h/day
- Recent cardiopulmonary resuscitation (CPR) (within current hospital stay)
- Body mass index (BMI) ≥ 40 kg/m2or weight ≥ 130 kg
- Moribund patients
- Decision to limit full care taken before obtaining informed consent
- Participation in another interventional study in the 3 months prior to randomization
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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| Study Director: | Jean-Jacques Garaud, MD | CEO and Medical Officer |
| 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 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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Septic Shock |
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Shock, Septic Shock Pathologic Processes Sepsis Infections |
Systemic Inflammatory Response Syndrome Inflammation Nangibotide Anti-Inflammatory Agents |