To demonstrate that Plerixafor is able to reduce the need for invasive mechanical ventilation or death in severe COVID-19 patients admitted in Intensive Care Unit (ICU)
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
acute respiratory failure related to COVID-19
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Proportion of patients with need for invasive mechanical ventilation or death
between randomization and D28
Secondary outcome
• Percentage of death (all-cause mortality)
• Number of Ventilator-free days
• Duration of invasive mechanical ventilation in survivors
• Number of ICU stay days
• Respiratory function at 3 months (FEV-1, FVC, PaO2, TLCO, 6-minute walk test)
• Ordinal Scale for Clinical Improvement (7 point-WHO scale)
• Level of consciousness (Alert, Voice, Pain, Unresponsive scale)
• SpO2 measured via pulse oxymetry and arterial blood gas: Partial pressure of
oxygen (PaO2), Partial pressure of carbon dioxide (PaCO2), Bicarbonate (HCO3),
Oxygen saturation (O2 Sat), pH, Base excess (when performed before intubation)
• Blood CRP, fibrinogen, D-dimers levels
• Incidence of treatment-emergent AEs (TEAEs), serious AEs (SAEs), and AEs of
special interest (AESIs),
• Incidence of Plerixafor discontinua-tion and withdrawals due to TEAEs
• WBC count and differential, RBC count, hemoglobin level, MCV, Reticulocyte
and Platelet counts
• Blood Chemistry (Creatinine, AST, ALT, total bilirubin, K, total Ca)
Background summary
Plerixafor is a chemical compound approved in Europe since 2009 and
commercialized under the tradename Mozobil® by Sanofi-Genzyme. It is indicated
in lymphoma and multiple myeloma (both types of blood cancer) to help collect
blood stem cells from the patient for storage and reintroduction
(transplantation). Plerixafor is considered an investigational drug in this
study because it has not been approved for marketing by any health authority
for the condition being studied (severe COVID-19 infection).
Plerixafor reduces migration of immature and inefficient white blood cells and
consequently the damages done by these cells. As observed in mice, plerixafor
is also expected to ameliorate the aspect of the lungs after a respiratory
viral infection.
Since severity of COVID-19 is associated with elevated blood and lung levels of
those type of white blood cells, plerixafor is considered as a promising
candidate to treat severe COVID-19 infection.
Study objective
To demonstrate that Plerixafor is able to reduce the need for invasive
mechanical ventilation or death in severe COVID-19 patients admitted in
Intensive Care Unit (ICU)
Study design
A randomized, double-blind, placebo-controlled, two parallel groups,
international multicenter trial to evaluate the effect of Plerixafor in acute
respiratory failure related to COVID-19.
Participants will be randomized in a 2:1 ratio to receive either Plerixafor
(n=100) or placebo (n=50) as a continuous IV infusion for 7 days (from D1 to
D8), in addition to standard of care (e.g. glucocorticoids*). Intervention
randomization will be stratified per investigational site.
Intervention
Plerixafor (Mozobil®) 30 microgrammes/kg/hour continuous intravenous infusion
for 7 days or Placebo similar modalities for infusion.
Study burden and risks
Preclinical data previously described suggest that plerixafor could reduce the
severity of COVID-19 lung injury in patients with acute respiratory failure.
See protocol 2.3 Benefit/Risk assessment
Campus de l'Institut Pasteur de Lille 1 rue du Professeur Calmette
Lille 59 000
FR
Campus de l'Institut Pasteur de Lille 1 rue du Professeur Calmette
Lille 59 000
FR
Listed location countries
Age
Inclusion criteria
• I1 Male or female >= 18 years of age,
• I2 Using contraceptive consistent with local regulations regarding the
methods of contraception for those participating in clinical studies,
• I3 Willing and able to provide written informed consent (or provided by
legally acceptable representative if he/she is present and if in line with
local regulations),
• I4 Admitted in ICU within 48 hours before randomization for COVID-19 related
respiratory failure.
* ICU or equivalent medical structure according to country specificities e.g.,
Acute Respiratory Care Unit, High Dependency Care Unit if they can provide:
* continuous IV infusion,
* continuous ECG, respiratory rate, percutaneous oxygen saturation screen
monitoring
* high flow nasal oxygen
• I5 Not requiring immediate (within 24-36 hours) invasive mechanical
ventilation according to investigator's judgment,
• I6 Confirmed pneumoniae due to SARS-CoV-2 with Laboratoryconfirmed SARS-CoV-2
infection as determined by RT-PCR (in nasopharynx or throat samples) or other
commercial or public health assay in any specimen, performed within 2 weeks
prior to randomization,
• I7 Acute respiratory failure requiring oxygen support (>= 5L/min) to achieve a
transcutaneous oxygen saturation > 94%,
• I8 Estimated glomerular filtration rate (eGFR) > 50 mL/min/1.73m² by the
CKD-EPI (Chronic Kidney Disease - Epidemiology Collaboration) equation.
Patients vaccinated against SARS-CoV-2 can be included in the study.
Before or during the whole study, patients may have or will receive standard of
care i.e.,
routinely administered in such patients in the country study site as per
current health
authorities* recommendations (e.g., glucocorticoids, tocilizumab, remdesivir
*.).
Exclusion criteria
• E1 Pregnancy or breast feeding,
• E2 Anticipated transfer to another hospital, which is not a study site within
72 hours of randomisation,
• E3 Need for Invasive mechanical ventilation at time of inclusion,
• E4 Evidence of uncontrolled bacterial pneumopathy or active infection other
than SARS-Cov-2 (laboratory confirmation),
• E5 Primitive pulmonary arterial hypertension,
• E6 Cardio-vascular co-morbidity:
o History of vascular ischemic events (myocardial infarction or stroke) or
congestive heart failure or peripheral arterial disease,
o History or current significant cardiac rhythm disorders (e.g., ventricular
tachycardia),
o Known medical history of proven symptomatic postural hypotension,
• E7 Known cancer (solid or blood) in the last 5 previous years or previous
haematological disorders
(malignancies and other chronic conditions) or having received bone marrow
transplant,
• E8 Inadequate haematological function defined by:
o Neutrophil count < 1.0 x 109/L,
o Haemoglobin < 9.0 g/dL (90 g/L),
o Platelets < 100 x 109/L,
• E9 Kaliemia < 3.5 mmol/L and/or total Calcemia < 2.2 mmol/L,
• E10 Inadequate hepatic function defined by Aspartate aminotransferase (AST)
and/or Alanine Aminotransferase (ALT) > 3 x upper limit of normal (ULN) and/or
Total bilirubin > 2 x ULN,
• E11 Patients with known allergy to Plerixafor or its excipients.
• E12 Previous (within 4 weeks) or current participation in another clinical
study other than an observational study.
• E13 Patients with auto immune disease treated or not,
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2021-001245-13-NL |
| CCMO | NL79887.091.22 |