Post-acute COVID-19 syndrome (PACS) MedDRA version: 24.1 Level: LLT Classification code 10085504 Term: Long COVID System Organ Class: 100000004862
Conditions
Sponsors
Hellenic Institute for the Study of Sepsis
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age equal to or above 18 years 2. Male or female gender 3. In the case of women of childbearing age and men, an adequate method of contraception should be used during the study. Contraception should be maintained for at least a period of 3 months after the discontinuation of treatment. As an adequate method of contraception, it is suggested: -male or female condom with or without spermicide -contraceptive cap, a diaphragm or contraceptive sponge with a spermicide Prior to admission to the study, a pregnancy test will be performed to exclude pregnancy to women of childbearing age. 4. Written informed consent provided by the patient. For subjects without decision-making capacity, informed consent must be obtained from a legally designated representative following the national legislation in the Member State where the trial is planned. 5. History of confirmed COVID-19 infection the last 90 days or more 6. Symptoms compatible with PACS (defined as at least one positive answer to the questionnaire for restriction of daily activities) lasting for more than 2 months 7. Serum IP-10 concentration greater than 250 pg/ml 8. Presence of at least ONE of the following two clinical conditions: Condition 1 Abnormal lung function test (defined as: DLCOcor =65 years) yes F.1.3.1 Number of subjects for this age range 91
Exclusion criteria
Exclusion criteria: • Age below 18 years • Denial for written informed consent • Any stage IV malignancy • Any primary immunodeficiency • Less than 1,500 neutrophils/mm3 • Known hypersensitivity to anakinra • Known lung fibrosis prior to COVID-19 • Medical history of pulmonary hypertension or chronic heart failure • Known chronic obstructive pulmonary disease GOLD stage 3 or 4 prior to COVID-19 • Known active tuberculosis (under treatment) or latent tuberculosis (by positive tuberculin test) • Oral or IV intake of corticosteroids at a daily dose equal or greater than 0.4 mg/kg prednisone for a period greater than the last 15 days. • Any anti-cytokine biological treatment the last one month • Severe hepatic failure defined as Child-Pugh stage of 3 • End-stage renal failure necessitating hemofiltration or peritoneal hemodialysis • Pregnancy or lactation. Women of child-bearing potential will be screened by a urine pregnancy test before inclusion in the study • Participation in any other interventional trial
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The PRECISION is a proof-of-concept, phase II randomized clinical trial aiming to evaluate the efficacy and safety of anakinra in patients with Post-Acute COVID Syndrome (PACS) of the pro-inflammatory respiratory phenotype. Improvement is measured by a composite endpoint, namely, the “Score of PACS progression reversal”;Secondary Objective: Not applicable;Primary end point(s): A composite primary endpoint will be applied. This endpoint will be named “Score of PACS progression reversal”. A positive score is defined differently for patients enrolled in the study because of Condition 1 or Condition 2. For patients enrolled in the study because of Condition 1, a positive score comprises at least two of the following evaluation elements: • At least 20% improvement of restrictive lung disease (increase of at least one of DLCOcor, TLC, FVC or FEV1/FVC) from baseline • No need for hospitalization ?r admission to the Emergency Department for any cause • No increase of the degree of lung fibrosis score in lung HRCT For patients enrolled in the study because of Condition 2, a positive score comprises at least two of the following evaluation elements: • At least 20% decrease of the total radiology score in lung HRCT OR Improved exercise capacity (defined as more than 30 meters improvement) in the 6min walk test (depending on which of the two criteria the patient was enrolled) • No need for hospitalization ?r admission to the Emergency Department for any cause • No increase of the degree of lung fibrosis score in lung HRCT The proportion of patients achieving the above composite endpoint compared to placebo at week 4 will be the primary study endpoint.;Timepoint(s) of evaluation of this end point: Week 4 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • The frequency of the Score of PACS progression reversal between patients receiving 8 weeks anakinra treatment compared to patients receiving 4 weeks anakinra treatment (+4 weeks of placebo) • Changes in cytokine production capacity of stimulated PBMCs at week 4 between the two arms of treatment • Change of each component of the score for the primary outcome at week 4 between the two arms of treatment • At least 10% decrease of the pulmonary artery pressure at week 4 between the two arms of treatment • At least 10% increase of LV ejection fraction (if abnormal at baseline) at week 4 between the two arms of treatment;Timepoint(s) of evaluation of this end point: Week 4, Week 8 | — |
Countries
Greece
Contacts
Public ContactPresident of the Board
Hellenic Institute for the Study of Sepsis
Outcome results
None listed