RecruitingPhase 2Phase 3NCT05926505

Safety and Efficacy of Anakinra Treatment for Patients With Post Acute Covid Syndrome

Safety and Efficacy of Anakinra Treatment for Patients With Persistent Respiratory Symptoms Post Acute Covid and Immune System Activation: the Precision Double-blind, Randomized Clinical Trial


Sponsor

Hellenic Institute for the Study of Sepsis

Enrollment

182 participants

Start Date

Sep 6, 2023

Study Type

INTERVENTIONAL

Conditions

Summary

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"


Eligibility

Min Age: 18 Years

Inclusion Criteria9

  • Age equal to or above 18 years
  • Male or female gender
  • 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.
  • 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.
  • History of confirmed COVID-19 infection the last 90 days or more
  • 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
  • Serum levels of IP-10 more than 250 pg/ml
  • Presence of ONE of the following two clinical conditions: Condition 1: Impaired Lung Function tests (defined as: DLCOcor \<76% AND TLC and/or FVC lower than 80% of predicted) Condition 2: At least a total radiology score in HRCT more than 20 OR walking of a distance less than 500m in the 6-minute walk test
  • If patients meet the criteria for both Conditions 1 and 2, they will be considered for randomization and evaluation for the primary endpoint as in Condition 1.

Exclusion Criteria16

  • 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

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Interventions

DRUGPlacebo

Placebo is injected subcutaneously once daily for 4 weeks. After the period of 4 weeks, patients allocated to arm 1 will be shifted to subcutaneous treatment with 100mg anakinra once daily for 4 weeks.

DRUGAnakinra 149 MG/ML Prefilled Syringe [Kineret]

Anakinra is injected subcutaneously as 100 mg once daily for 4 weeks. After the first period the patients will be randomized 1:1 to continue receiving subcutaneous treatment with 100mg anakinra once daily for 4 weeks or placebo once daily for 4 weeks.


Locations(24)

Out-patient long-COVID department, Jena University Hospital

Jena, Germany

Out-patient long-COVID department, Patras University General Hospital

Pátrai, Achaia, Greece

Out-patient long-COVID department III, Evangelismos Athens General Hospital

Athens, Attica, Greece

Out-patient long-COVID department I, Sotiria Athens Hospital of Chest Diseases

Athens, Attica, Greece

Out-patient long-COVID department II, Sotiria Athens Hospital of Chest Diseases

Athens, Attica, Greece

Out-patient long-COVID department IV, Sotiria Athens Hospital of Chest Diseases

Athens, Attica, Greece

Out-patient long-COVID department, Laiko General Hospital

Athens, Attica, Greece

2nd Department of Propedeutic Medicine, ATTIKON University General Hospital

Chaïdári, Attica, Greece

4th Department of Internal Medicine, ATTIKON University General Hospital

Chaïdári, Attica, Greece

Out-patient long-COVID department, Ioannina University General Hospital

Ioannina, Ioannina, Greece

Out-patient long-COVID department, Tzaneion Piraeus General Hospital

Piraeus, Piraeus, Greece

Out-patient long-COVID department, Alexandroupolis University General Hospital

Alexandroupoli, Greece

Out-patient long-COVID department X, Sotiria Athens Hospital of Chest Diseases

Athens, Greece

Out-patient long-COVID department, University Hospital of Larissa

Larissa, Greece

Out-patient long-COVID department II, Thriasio General Hospital of Elefsina

Magoula, Greece

Out-patient long-COVID department I, Thriasio General Hospital of Elefsina

Magoula, Greece

Out-patient long-COVID department, AHEPA Hospital of Thessaloniki

Thessaloniki, Greece

Infectious Diseases Clinic, Ospedale Policlinico San Martino IRCCS and Department of Health Sciences, University of Genova, Genoa, Italy

Genova, Italy

Department of Internal Medicine, Hospital of Jesolo, Italy

Jesolo, Italy

Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), IRCCS Ospedale San Raffaele & Vita-Salute San Raffaele University, Milan, Italy

Milan, Italy

Infectious Diseases Clinic, University of Modena, Italy

Modena, Italy

Dipartimento Scienze di Laboratorio e Infettivologiche - Fondazione Policlinico Gemelli IRCCS, Roma Italy

Rome, Italy

ID Respiratory Unit, Spallanzani Institute of Rome, Italy

Rome, Italy

Department of Pulmonary Medicine, Barcelona University Hospital

Barcelona, Spain

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NCT05926505


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