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

NCT ID: NCT05926505

Last Updated: 2026-01-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2/PHASE3

Total Enrollment

182 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-09-06

Study Completion Date

2028-03-31

Brief Summary

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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"

Detailed Description

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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".

Conditions

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Post-Acute COVID-19 Syndrome Post-Acute COVID-19 Long COVID

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Placebo

Placebo is injected subcutaneously once daily for 4 weeks.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

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.

Anakinra

Anakinra is injected subcutaneously as 100 mg once daily for 4 weeks.

Group Type EXPERIMENTAL

Anakinra 149 MG/ML Prefilled Syringe [Kineret]

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type 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.

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hellenic Institute for the Study of Sepsis

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Evangelos Giamarelos-Bourboulis, MD,PhD

Role: STUDY_CHAIR

Hellenic Institute for the Study of Sepsis

Locations

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Out-patient long-COVID department, Jena University Hospital

Jena, , Germany

Site Status NOT_YET_RECRUITING

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

Pátrai, Achaia, Greece

Site Status RECRUITING

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

Athens, Attica, Greece

Site Status NOT_YET_RECRUITING

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

Athens, Attica, Greece

Site Status RECRUITING

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

Athens, Attica, Greece

Site Status RECRUITING

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

Athens, Attica, Greece

Site Status RECRUITING

Out-patient long-COVID department, Laiko General Hospital

Athens, Attica, Greece

Site Status RECRUITING

2nd Department of Propedeutic Medicine, ATTIKON University General Hospital

Chaïdári, Attica, Greece

Site Status RECRUITING

4th Department of Internal Medicine, ATTIKON University General Hospital

Chaïdári, Attica, Greece

Site Status RECRUITING

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

Ioannina, Ioannina, Greece

Site Status RECRUITING

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

Piraeus, Piraeus, Greece

Site Status RECRUITING

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

Alexandroupoli, , Greece

Site Status RECRUITING

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

Athens, , Greece

Site Status RECRUITING

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

Larissa, , Greece

Site Status NOT_YET_RECRUITING

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

Magoula, , Greece

Site Status RECRUITING

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

Magoula, , Greece

Site Status RECRUITING

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

Thessaloniki, , Greece

Site Status RECRUITING

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

Genova, , Italy

Site Status NOT_YET_RECRUITING

Department of Internal Medicine, Hospital of Jesolo, Italy

Jesolo, , Italy

Site Status NOT_YET_RECRUITING

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

Milan, , Italy

Site Status NOT_YET_RECRUITING

Infectious Diseases Clinic, University of Modena, Italy

Modena, , Italy

Site Status NOT_YET_RECRUITING

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

Rome, , Italy

Site Status NOT_YET_RECRUITING

ID Respiratory Unit, Spallanzani Institute of Rome, Italy

Rome, , Italy

Site Status NOT_YET_RECRUITING

Department of Pulmonary Medicine, Barcelona University Hospital

Barcelona, , Spain

Site Status NOT_YET_RECRUITING

Countries

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Germany Greece Italy Spain

Central Contacts

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Evangelos Giamarelos-Bourboulis, MD,PhD

Role: CONTACT

00302105831994

Facility Contacts

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P. Reuken

Role: primary

Argyrios Tzouvelekis, MD, PhD

Role: primary

Vassiliki Georgiopoulou, MD

Role: backup

6956469542

Paraskevi Katsaounou, MD, PhD

Role: primary

6932668142

Garyphallia Poulakou, MD, PhD

Role: primary

6945597583

Nikoletta Rovina, MD, PhD

Role: primary

6945830212

Ioannis Dimitroulis, MD

Role: primary

6932666007

Michael Samarkos, MD, PhD

Role: primary

6977470306

Panagiotis Chalvatsiotis, MD, PhD

Role: primary

6972275955

Evangelos J. Giamarellos-Bourboulis, MD, PhD

Role: primary

6945521800

Christos Psarrakis, MD

Role: backup

6980969012

Charalampos Milionis, MD, PhD

Role: primary

6944521512

Styliani Gerakari, MD

Role: primary

6973308684

Periklis Panagopoulos, MD, PhD

Role: primary

6944410495

Ilias Kainis, DM, PhD

Role: primary

6947528476

George Dalekos, MD, PhD

Role: primary

2413502285 / 6937759699

Konstantina Iliopoulou, MD

Role: primary

6973391426

Styliani Sympardi, MD

Role: primary

6971863078

Symeon Metallidis, MD, PhD

Role: primary

6944361931

M. Bassetti, MD, PhD

Role: primary

Francesco Saverio-Serino, MD

Role: primary

L. Dagna

Role: primary

Giovanni Guaraldi, MD, PhD

Role: primary

M. Fantoni

Role: primary

Fabrizio Palmieri, MD

Role: primary

A. Torres

Role: primary

Other Identifiers

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2023-000102-25

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

PRECISION

Identifier Type: -

Identifier Source: org_study_id

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