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

January 6, 2026 updated by: Hellenic Institute for the Study of Sepsis

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

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"

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

People with COVID-19 might have sustained post-infection sequelae, known as Post-Acute Covid Syndrome (PACS). A recent consensus definition by an international panel of 265 patients, clinicians, researchers, and WHO staff suggests that post-COVID-19 condition occurs in individuals with a history of probable or confirmed SARS-CoV-2 infection, usually 3 months from the onset, with symptoms that last for at least 2 months and cannot be explained by an alternative diagnosis. Common symptoms include fatigue, shortness of breath, and cognitive dysfunction and generally have an impact on everyday functioning.

The role of immune dysregulation in PACS is indirectly supported from the findings of the SAVE-MORE randomized clinical trial, in which patients with moderate and severe COVID-19, were 1:2 randomized to treatment with placebo or anakinra once daily for 10 days. The primary endpoint was the distribution of the frequencies of patients in the 11 points of the WHO clinical progression scale (CPS) by day 28. Patients' follow-up until day 90 showed significant reduction of the incidence of PACS; this was 24.4% among placebo-treated patients and 15.7% among patients treated with anakinra.

After the end of the SAVE-MORE trial, the understanding of the immune activation of PACS and the development of tools for the evaluation of patients have become the main aims of the Hellenic Institute for the study of sepsis (HISS) group. More precisely, patients with medical history of COVID-19 pneumonia during three separate time periods and matched comparators for age, sex, comorbidities, and state of vaccination were followed up and evaluated for PACS. Main findings can be summarized as follows:

  1. For at least one year after acute COVID-19 there is considerable immune dysregulation involving both the innate and the adaptive responses.
  2. Patients with PACS may be classified into four main phenotype clusters: fatigue involving 70.8%, respiratory cluster involving 33.2%, systemic symptoms involving 17.7% and other symptoms involving 26.1%.
  3. The risk for progression into PACS was significantly lower among patients treated with anakinra in the acute stage (odds ratio 0.59, p: 0.017) showing a role of IL-1 for the progression into PACS.
  4. Patients with fatigue bring distinct immunotype compared to the respiratory cluster.
  5. IP-10 (interferon-gamma-induced protein-10) at levels more than 250 pg/ml has sensitivity 99.3%, specificity 90.9%, positive predictive value (PPV) 97.9% and negative predictive value (NPV) 97.6% for the diagnosis of the post acute COVID immune dysregulation.

PRECISION is a proof-of-concept, randomized clinical trial (RCT) aiming to evaluate the efficacy and safety of anakinra in patients with PACS in improving the clinical and immunological state over 4 to 8 weeks as measured by a composite endpoint, namely, the "Score of PACS progression reversal".

Study Type

Interventional

Enrollment (Estimated)

182

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Evangelos Giamarelos-Bourboulis, MD,PhD
  • Phone Number: 00302105831994
  • Email: egiamarel@med.uoa.gr

Study Locations

  • Germany
      • Jena, Germany
        • Not yet recruiting
        • Out-patient long-COVID department, Jena University Hospital
        • Contact:
          • P. Reuken
  • Greece
      • Alexandroupoli, Greece, 68100
        • Recruiting
        • Out-patient long-COVID department, Alexandroupolis University General Hospital
        • Contact:
      • Athens, Greece, 115 27
        • Recruiting
        • Out-patient long-COVID department X, Sotiria Athens Hospital of Chest Diseases
        • Contact:
      • Larissa, Greece, 41110
      • Magoula, Greece, 196 00
        • Recruiting
        • Out-patient long-COVID department II, Thriasio General Hospital of Elefsina
        • Contact:
      • Magoula, Greece, 19600
        • Recruiting
        • Out-patient long-COVID department I, Thriasio General Hospital of Elefsina
        • Contact:
      • Thessaloniki, Greece, 54636
        • Recruiting
        • Out-patient long-COVID department, AHEPA Hospital of Thessaloniki
        • Contact:
    • Achaia
    • Attica
      • Athens, Attica, Greece, 10676
        • Not yet recruiting
        • Out-patient long-COVID department III, Evangelismos Athens General Hospital
        • Contact:
      • Athens, Attica, Greece, 11527
        • Recruiting
        • Out-patient long-COVID department I, Sotiria Athens Hospital of Chest Diseases
        • Contact:
      • Athens, Attica, Greece, 11527
        • Recruiting
        • Out-patient long-COVID department II, Sotiria Athens Hospital of Chest Diseases
        • Contact:
      • Athens, Attica, Greece, 11527
        • Recruiting
        • Out-patient long-COVID department IV, Sotiria Athens Hospital of Chest Diseases
        • Contact:
      • Athens, Attica, Greece, 11527
        • Recruiting
        • Out-patient long-COVID department, Laiko General Hospital
        • Contact:
      • Chaïdári, Attica, Greece, 12462
        • Recruiting
        • 2nd Department of Propedeutic Medicine, ATTIKON University General Hospital
        • Contact:
          • Panagiotis Chalvatsiotis, MD, PhD
          • Phone Number: 6972275955
          • Email: pahalv@gmail.com
      • Chaïdári, Attica, Greece, 12462
        • Recruiting
        • 4th Department of Internal Medicine, ATTIKON University General Hospital
        • Contact:
        • Contact:
    • Ioannina
      • Ioannina, Ioannina, Greece, 455 00
        • Recruiting
        • Out-patient long-COVID department, Ioannina University General Hospital
        • Contact:
          • Charalampos Milionis, MD, PhD
          • Phone Number: 6944521512
          • Email: hmilioni@uoi.gr
    • Piraeus
      • Piraeus, Piraeus, Greece, 18536
        • Recruiting
        • Out-patient long-COVID department, Tzaneion Piraeus General Hospital
        • Contact:
  • Italy
      • Genova, Italy
        • Not yet recruiting
        • Infectious Diseases Clinic, Ospedale Policlinico San Martino IRCCS and Department of Health Sciences, University of Genova, Genoa, Italy
        • Contact:
          • M. Bassetti, MD, PhD
      • Jesolo, Italy
        • Not yet recruiting
        • Department of Internal Medicine, Hospital of Jesolo, Italy
        • Contact:
          • Francesco Saverio-Serino, MD
      • Milan, Italy
        • Not yet recruiting
        • Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), IRCCS Ospedale San Raffaele & Vita-Salute San Raffaele University, Milan, Italy
        • Contact:
          • L. Dagna
      • Modena, Italy
        • Not yet recruiting
        • Infectious Diseases Clinic, University of Modena, Italy
        • Contact:
          • Giovanni Guaraldi, MD, PhD
      • Rome, Italy
        • Not yet recruiting
        • Dipartimento Scienze di Laboratorio e Infettivologiche - Fondazione Policlinico Gemelli IRCCS, Roma Italy
        • Contact:
          • M. Fantoni
      • Rome, Italy
        • Not yet recruiting
        • ID Respiratory Unit, Spallanzani Institute of Rome, Italy
        • Contact:
          • Fabrizio Palmieri, MD
  • Spain
      • Barcelona, Spain
        • Not yet recruiting
        • Department of Pulmonary Medicine, Barcelona University Hospital
        • Contact:
          • A. Torres

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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 levels of IP-10 more than 250 pg/ml
  8. 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 Criteria:

  1. Age below 18 years
  2. Denial for written informed consent
  3. Any stage IV malignancy
  4. Any primary immunodeficiency
  5. Less than 1,500 neutrophils/mm3
  6. Known hypersensitivity to anakinra
  7. Known lung fibrosis prior to COVID-19
  8. Medical history of pulmonary hypertension or chronic heart failure
  9. Known chronic obstructive pulmonary disease GOLD stage 3 or 4 prior to COVID-19
  10. Known active tuberculosis (under treatment) or latent tuberculosis (by positive tuberculin test)
  11. 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.
  12. Any anti-cytokine biological treatment the last one month
  13. Severe hepatic failure defined as Child-Pugh stage of 3
  14. End-stage renal failure necessitating hemofiltration or peritoneal hemodialysis
  15. Pregnancy or lactation. Women of child-bearing potential will be screened by a urine pregnancy test before inclusion in the study
  16. Participation in any other interventional trial

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Placebo is injected subcutaneously once daily for 4 weeks.
Drug: Placebo
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.
Experimental: Anakinra
Anakinra is injected subcutaneously as 100 mg once daily for 4 weeks.
Drug: Anakinra 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Score of PACS progression reversal
Time Frame: Through study completion,an average of 2 years

A positive score is defined differently for patients enrolled in the study because of Condition 1 or Condition 2. For patients enrolled in Condition 1, a positive score comprises at least two of the following: 1. At least 20% improvement of restrictive lung disease from baseline 2.No need for hospitalization οr admission to the Emergency Department 3. No increase of the degree of lung fibrosis score in lung HRCT For patients enrolled in Condition 2, a positive score comprises at least two of the following: 1. At least 20% decrease of the total score in lung HRCT OR Improved exercise capacity in the 6min walk test. 2.No need for hospitalization οr admission to the Emergency Department. 3.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.
Through study completion,an average of 2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
Time Frame: Through study completion,an average of 2 years
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).
Through study completion,an average of 2 years
At least 10% decrease of the pulmonary artery pressure at week 4 between the two arms of treatment.
Time Frame: Through study completion,an average of 2 years
At least 10% decrease of the pulmonary artery pressure at week 4 between the two arms of treatment.
Through study completion,an average of 2 years
At least 10% increase of LV ejection fraction (if abnormal at baseline) at week 4 between the two arms of treatment.
Time Frame: Through study completion,an average of 2 years
At least 10% increase of LV ejection fraction (if abnormal at baseline) at week 4 between the two arms of treatment
Through study completion,an average of 2 years
Changes of concentration of cytokines produced by stimulated PBMCs at week 4 between the two arms of treatment.
Time Frame: Through study completion,an average of 2 years
Changes of concentration of cytokines produced by stimulated PBMCs at week 4 between the two arms of treatment.
Through study completion,an average of 2 years
Change of each component of the score for the primary outcome at week 4 between the two arms of treatment.
Time Frame: Through study completion,an average of 2 years
Change of each component of the score for the primary outcome at week 4 between the two arms of treatment. Post-acute COVID-19 syndrome (PACS) score. The higher the score, the worst the patients' outcome. PACS score ranges between 0-16.
Through study completion,an average of 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hellenic Institute for the Study of Sepsis

Investigators

  • Study Chair: Evangelos Giamarelos-Bourboulis, MD,PhD, Hellenic Institute for the Study of Sepsis

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 6, 2023

Primary Completion (Estimated)

March 1, 2028

Study Completion (Estimated)

March 1, 2028

Study Registration Dates

First Submitted

June 28, 2023

First Submitted That Met QC Criteria

June 28, 2023

First Posted (Actual)

July 3, 2023

Study Record Updates

Last Update Posted (Actual)

January 8, 2026

Last Update Submitted That Met QC Criteria

January 6, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PRECISION
  • 2023-000102-25 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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