The overall purpose of the trial is to evaluate the efficacy and safety of possible combination antiviral therapy DAA (remdesivir + nirmatrelvir/r)∞ versus the reference monotherapy (nirmatrelvir/r alone) and to assess the efficacy and safety of increasing the nirmatrelvir/r course from 5- to 10 days in immunocompromised patients diagnosed with asymptomatic or mild to moderate COVID-19.
Laboratory confirmed SARS-CoV-2 infection by RT-PCR or positive antigenic test (commercialized assay)
Asymptomatic or mild to moderate COVID-19 (WHO progression scale <5. Patients receiving oxygen therapy for reasons other than a pulmonary COVID-19 are eligible).
≥ 16 years of age (for patients recruited in Italy and in Norway, ≥ 18 years of age);
Immunocompromised as defined by ≥ 1 risk factors for severe COVID-19 as assessed by the FOPH list (criteria 5: diseases/treatments leading to immune suppression) or other immunosuppression criteria such as Severe immunosuppression (e.g., HIV infection with CD4 + T cell count <350 / µl) Neutropenia (<1000 neutrophils / µl) ≥1 week Lymphocytopenia (<200 lymphocytes/µl) On dialysis treatment Hereditary immunodeficiencies Intake of drugs which suppress the immune system (e.g. glucocorticoids for a long time [an equivalent dose of prednisone >20 mg/day > 3 months], monoclonal antibodies, cytostatics, biological products, everolimus, mTOR inhibitors etc.) in the last 12 months Active cancer under cytostatics or targeted therapy known to be immunosuppressive (e.g., platinum salts, cyclophosphamide, anthracyclines, taxanes, 5-fluorouracil, gemcitabine, purine inhibitors, proteasome inhibitors) or associated with hematologic toxicity (neutropenia, lymphopenia), for example sunitinib, imatinib, regorafenib. Aggressive lymphomas (all types) Acute lymphatic leukemia Acute myeloid leukemia Acute promyelocytic leukemia T prolymphocytic leukemia Primary central nervous system lymphoma Stem cell transplantation Light chain amyloidosis Chronic lymphoid leukemia Multiple myeloma Sickle cell disease Bone marrow transplant Organ transplant Being on the waiting list for an organ transplant
SARS-CoV-2 PCR ≥30 CT at screening
Hypersensitivity to study drugs (active substance(s) or excipients)
Body weight < 40 kg
AST and/or ALT > 5 times the upper limit
Parallel
Paxlovid 5 days
DrugNirmatrelvir/r 300mg/100 mg bid will be given for 5 days, orally. Nirmatrelvir/r is a combination of two molecules: nirmatrelvir which is a protease inhibitor (against 3CL) and ritonavir which has a booster role. Nirmatrelvir/r (marketed by Pfizer under the brand name Paxlovid®) is indicated for the treatment of COVID-19 in adults who do not require supplemental oxygen and who are at increased risk for progressing to severe COVID-19.
Paxlovid 10 days
DrugNirmatrelvir/r 300mg/100 mg bid will be given for 10 days, orally.
Veklury
DrugRemdesivir "flash", 200mg, intravenous. Remdesivir (marketed by Gilead under de brand name Veklury®) is indicated in patients with pneumonia requiring supplemental oxygen (inpatients), as well as in outpatients who are at increased risk of progressing to severe COVID-19. The mode of action characterize remdesivir as a direct-acting antiviral compound.
Percentage of patients with SARS-CoV-2 viral load (threshold cicle (Ct) <32) by real-time RT-PCR in nasopharyngeal swabs at Day 10 after treatment initiation.
SARS-CoV-2 viral load is measured in nasopharyngeal swabs by real-time RT-PCR
Percentage of patients with SARS-CoV-2 viral load (threshold cicle <32 CT) by real-time RT-PCR in nasopharyngeal swabs at Day5, Day14 and Day21 after treatment initiation
SARS-CoV-2 viral load is measured in nasopharyngeal swabs by real-time RT-PCR
Percentage of patients with detectable SARS-CoV-2 viremia at Day5, Day10 and Day14
SARS-CoV-2 viremia is measured from plasma samples by real-time RT-PCR
Decrease of SARS-CoV-2 viral load measured by copies/ml by nasopharyngeal swab at Day5, Day10, Day14, Day21 and in blood samples at Day5, Day10 and Day14 comparatively to screening
SARS-CoV-2 viral load is measured in nasopharyngeal swabs and in blood samples by real-time RT-PCR
Number of de novo emergence of mutations on nasopharyngeal RT-PCR at Day5, Day10, Day14 and Day21 comparatively to screening
Emergence of mutations is measured in nasopharyngeal swabs by genotyping techniques
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