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Due to poor recruitment.
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The clinical trial is designed as a prospective, multi-center, double-blind, randomised, placebo-controlled, interventional trial to assess safety, tolerability and efficacy of Adrecizumab (on top of SOC) in patients with COVID-19, and to evaluate if improvement of vascular integrity with Adrecizumab on top of SOC is superior to placebo/ control substance (NaCl 0.9%) on top of SOC in reduction of morbidity and mortality endpoints in patients with COVID-19.
The main reason for admission to ICU and need for mechanical ventilation of these patients is acute lung injury within a broad pneumonic spectrum, increased ventricular filling pressures and resulting congestion. It is hypothesized, that Adrenomedullin (ADM) is a key player in the (dys)-regulation of vascular integrity (Figure 2). Adrecizumab is the first-in-class humanized monoclonal anti-Adrenomedullin antibody, and acts as a long-lasting plasma Adrenomedullin enhancer stabilizing barrier function at a reasonable safety profile. The mode of action for the anti-Adrenomedullin antibody Adrecizumab has been developed on the basis of published data, own experimental data and theoretical considerations.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Adrecizumab (HAM 8101) | Experimental | Adrecizumab (HAM 8101) on top of standard of care. Adrecizumab (HAM8101) is a humanized IgG1 monoclonal antibody (mAb). 2 mg/kg body weight Adrecizumab diluted in up to 100 mL saline as single dose infusion. |
|
| Placebo/ control substance (NaCl 0.9%) | Placebo Comparator | 100 mL saline as single dose infusion |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Adrecizumab (HAM 8101) | Biological | Drip infusion over 60 minutes. |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Time to clinical improvement | Time to clinical improvement, defined as the time from randomization to an improvement of two points (from the status at randomization) on the World Health Organisation 8-point ordinal scale or live discharge from the hospital, whichever came first. WHO 8-point ordinal scale
| 90 days |
| Measure | Description | Time Frame |
|---|---|---|
| Clinical status at day 28, as measured on the WHO 8-point ordinal scale | Please see Outcome 1 for details on WHO 8-point ordinal scale | 28 days |
| Survival (time-to-event) until day 28 and end of follow-up (90 days) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Stefan Kluge, MD | University Medical Center Hamburg-Eppendorf - Department of Intensive Care Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Charité | Berlin | Germany | ||||
| Universitätsklinikum Essen |
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| ID | Term |
|---|---|
| D000086382 | COVID-19 |
| D055371 | Acute Lung Injury |
| ID | Term |
|---|---|
| D011024 | Pneumonia, Viral |
| D011014 | Pneumonia |
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
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| ID | Term |
|---|---|
| C000706631 | enibarcimab |
| D012965 | Sodium Chloride |
| ID | Term |
|---|---|
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
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| Placebo |
| Drug |
Drip infusion over 60 minutes |
|
|
| 90 days |
| Rate of invasive mechanical ventilation until day 28 and day 90 | defined as use of endotracheal or tracheostomy tube assisted ventilation | 28 and 90 days |
| Length of invasive mechanical ventilation until day 28 and day 90 | defined as use of endotracheal or tracheostomy tube assisted ventilation | 28 and 90 days |
| Rate of ECMO therapy until day 28 and day 90 | 28 and 90 days |
| Length of ECMO therapy until day 28 and day 90 | 28 and 90 days |
| Length of stay at ICU after application of IMP up to a total of 90 days | 90 days |
| Length of hospital stay after application of IMP up to a total of 90 days | 90 days |
| All-cause rehospitalisation within 90 days | 90 days |
| Rate of renal replacement therapy until day 28 and day 90 | 28 and 90 days |
| Change in clinical status on the WHO 8-point ordinal scale for COVID-19 at days 7, 28, and 90 | Please see Outcome 1 for Details in WHO 8-point ordinal scale | 7, 28 and 90 days |
| Change in SOFA score sum (only during hospitalization on ICU) with-in 24 hours of IMP administration (start of infusion), 48 hours, day 7 post-infusion | 24 hours, 48 hours and 7 days post-infusion |
| Between-group difference in life quality as assessed by EQ-5D-5L at discharge, day 28, day 90 | 28 and 90 days |
| Essen |
| Germany |
| Universitätsklinikum Frankfurt | Frankfurt | Germany |
| Universitätsklinikum Freiburg | Freiburg im Breisgau | Germany |
| Universitätsmedizin Göttingen | Göttingen | Germany |
| University Medical Center Hamburg Eppendorf | Hamburg | 20246 | Germany |
| Medical School Hanover | Hanover | 30625 | Germany |
| Universitätsklinikum Mannheim | Mannheim | Germany |
| Klinikum rechts der Isar TU München | München | Germany |
| LMU München | München | Germany |
| Universitätsklinikum Regensburg | Regensburg | Germany |
| Universitätsklinikum Tübingen | Tübingen | Germany |
| Universitätsklinikum Ulm | Ulm | Germany |
| D014777 |
| Virus Diseases |
| D018352 | Coronavirus Infections |
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D055370 | Lung Injury |
| D017670 |
| Sodium Compounds |