Study Results
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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COMPLETED
PHASE2
219 participants
INTERVENTIONAL
2023-05-01
2024-11-28
Brief Summary
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Detailed Description
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Hypothesis: Nirmatrelvir/ritonavir (Paxlovid®) improves health-related quality of life measured using the EQ-5D-5L VAS scale, as compared to placebo/ritonavir, in objective and pre-defined clinical phenotypes: postural orthostatic tachycardia syndrome (POTS), microvascular dysfunction, inappropriate sinus tachycardia, persistent fever, post exertional malaise (PEM), fatigue, brain fog, dyspnea, dysfunctional breathing patterns or inflammatory phenotypes (increased plasma D-dimer, CRP, ESR and ferritin).
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
QUADRUPLE
Study Groups
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Nirmatrelvir/ritonavir
Oral nirmatrelvir/ritonavir (Paxlovid) 300/100 mg twice daily for 15 days
Nirmatrelvir/ritonavir
300/100 mg tablet twice daily (q12h) administered orally for 15 days
Placebo/ritonavir
Oral placebo/ritonavir 100 mg twice daily for 15 days
Placebo/ritonavir
100mg tablet twice daily (q12h) administered orally for 15 days
Interventions
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Nirmatrelvir/ritonavir
300/100 mg tablet twice daily (q12h) administered orally for 15 days
Placebo/ritonavir
100mg tablet twice daily (q12h) administered orally for 15 days
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
2. ≥18 years of age at the time of the Screening Visit.
3. Post-acute COVID-19 syndrome (PACS) according to the WHO definition.
4. EQ-5D-5L VAS ≤ 50
5. All fertile participants must agree to use a highly effective method of contraception for the duration of the study and 28 days after last intake of the IMP.
Exclusion Criteria
2. Renal function eGFR eGFRCysC \< 60 mL/min/1.73 m2.
3. Not able to comply with the study protocol.
4. Previous Paxlovid treatment.
5. Pregnancy or breastfeeding.
6. Drug-drug interaction with ongoing treatment, including concomitant use of any medications or substances that are strong inducers of CYP3A4 within 28 days prior to first dose of nirmatrelvir/ritonavir and during study treatment.
7. Participants who are planning or considering vaccination (including boosters) through Study Day 45.
8. Active COVID-19 infection as verified by SARS CoV-2 positive antigen test.
9. Self-reported medical conditions, including:
1. Type 1 or Type 2 diabetes mellitus.
2. Chronic kidney disease.
3. Neurodevelopmental disorders (e.g., cerebral palsy, Down's syndrome) or other conditions that confer medical complexity (e.g., genetic or metabolic syndromes and severe congenital anomalies).
4. Active cancer other than localized skin cancer, including those requiring treatment including palliative treatment), as long as the treatment is not among the prohibited medications that must be administered/continued during the trial period.
5. Immunosuppressive disease (e.g., bone marrow or organ transplantation or primary immune deficiencies) OR prolonged use of immune-weakening medications:
i. Has received corticosteroids equivalent to prednisone ≥20 mg daily for at least 14 consecutive days within 30 days prior to study entry.
ii. Has received treatment with biologics (e.g., infliximab, ustekinumab, etc.), immunomodulators (e.g., methotrexate, 6MP, azathioprine, etc.), or cancer chemotherapy within 90 days prior to study entry.
iii. HIV infection with CD4+ cell count \<200/mm3.
10. History of hospitalization for the medical treatment of acute COVID-19
11. Current need for hospitalization or anticipated need for hospitalization within 48 hours after randomization in the clinical opinion of the site investigator.
12. Prior/Concomitant Therapy:
1. Current or expected use of any medications or substances that are highly dependent on CYP3A4 for clearance, and for which elevated plasma concentrations may be associated with serious and/or life-threatening events during treatment and for 4 days after the last dose of nirmatrelvir/ritonavir. List of potential interactions provided by Pfizer provided in Appendix A.
2. Has received or is expected to receive monoclonal antibody treatment, antiviral treatment (e.g., molnupiravir), or convalescent COVID-19 plasma.
Prior/Concurrent Clinical Study Experience:
13. Is unwilling to abstain from participating in another interventional clinical study with an investigational compound or device, including those for post-COVID-19 therapeutics, through the long-term follow-up visit.
14. Previous administration with any investigational drug or vaccine within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of study intervention used in this study (whichever is longer).
15. Known prior participation in this trial or other trial involving nirmatrelvir.
Diagnostic Assessments:
16. Known history of any of the following abnormalities in clinical laboratory tests (within past 6 months of the screening visit):
* AST or ALT level ≥2.5 X ULN
* Total bilirubin ≥2 X ULN (≥3 X ULN for Gilbert's syndrome)
18 Years
ALL
No
Sponsors
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Karolinska University Hospital
OTHER
Pfizer
INDUSTRY
Karolinska Institutet
OTHER
Responsible Party
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Petter Brodin
Principal Investigator
Principal Investigators
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Michael Runold, MD, PhD
Role: PRINCIPAL_INVESTIGATOR
Karolinska University Hospital
Locations
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Karolinska Institutet
Stockholm, , Sweden
Countries
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References
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Caruso D, Guido G, Zerunian M, Polidori T, Lucertini E, Pucciarelli F, Polici M, Rucci C, Bracci B, Nicolai M, Cremona A, De Dominicis C, Laghi A. Post-Acute Sequelae of COVID-19 Pneumonia: Six-month Chest CT Follow-up. Radiology. 2021 Nov;301(2):E396-E405. doi: 10.1148/radiol.2021210834. Epub 2021 Jul 27.
Han X, Fan Y, Alwalid O, Li N, Jia X, Yuan M, Li Y, Cao Y, Gu J, Wu H, Shi H. Six-month Follow-up Chest CT Findings after Severe COVID-19 Pneumonia. Radiology. 2021 Apr;299(1):E177-E186. doi: 10.1148/radiol.2021203153. Epub 2021 Jan 26.
Ceban F, Ling S, Lui LMW, Lee Y, Gill H, Teopiz KM, Rodrigues NB, Subramaniapillai M, Di Vincenzo JD, Cao B, Lin K, Mansur RB, Ho RC, Rosenblat JD, Miskowiak KW, Vinberg M, Maletic V, McIntyre RS. Fatigue and cognitive impairment in Post-COVID-19 Syndrome: A systematic review and meta-analysis. Brain Behav Immun. 2022 Mar;101:93-135. doi: 10.1016/j.bbi.2021.12.020. Epub 2021 Dec 29.
Goh D, Lim JCT, Fernaindez SB, Joseph CR, Edwards SG, Neo ZW, Lee JN, Caballero SG, Lau MC, Yeong JPS. Case report: Persistence of residual antigen and RNA of the SARS-CoV-2 virus in tissues of two patients with long COVID. Front Immunol. 2022 Sep 5;13:939989. doi: 10.3389/fimmu.2022.939989. eCollection 2022.
Visvabharathy L, Orban ZS, Koralnik IJ. Case report: Treatment of long COVID with a SARS-CoV-2 antiviral and IL-6 blockade in a patient with rheumatoid arthritis and SARS-CoV-2 antigen persistence. Front Med (Lausanne). 2022 Sep 23;9:1003103. doi: 10.3389/fmed.2022.1003103. eCollection 2022.
Hammond J, Leister-Tebbe H, Gardner A, Abreu P, Bao W, Wisemandle W, Baniecki M, Hendrick VM, Damle B, Simon-Campos A, Pypstra R, Rusnak JM; EPIC-HR Investigators. Oral Nirmatrelvir for High-Risk, Nonhospitalized Adults with Covid-19. N Engl J Med. 2022 Apr 14;386(15):1397-1408. doi: 10.1056/NEJMoa2118542. Epub 2022 Feb 16.
Toussi SS, Neutel JM, Navarro J, Preston RA, Shi H, Kavetska O, LaBadie RR, Binks M, Chan PLS, Demers N, Corrigan B, Damle B. Pharmacokinetics of Oral Nirmatrelvir/Ritonavir, a Protease Inhibitor for Treatment of COVID-19, in Subjects With Renal Impairment. Clin Pharmacol Ther. 2022 Oct;112(4):892-900. doi: 10.1002/cpt.2688. Epub 2022 Jul 5.
Sundaram A, Vaughan B, Kost K, Bankole A, Finer L, Singh S, Trussell J. Contraceptive Failure in the United States: Estimates from the 2006-2010 National Survey of Family Growth. Perspect Sex Reprod Health. 2017 Mar;49(1):7-16. doi: 10.1363/psrh.12017. Epub 2017 Feb 28.
Swank Z, Senussi Y, Manickas-Hill Z, Yu XG, Li JZ, Alter G, Walt DR. Persistent Circulating Severe Acute Respiratory Syndrome Coronavirus 2 Spike Is Associated With Post-acute Coronavirus Disease 2019 Sequelae. Clin Infect Dis. 2023 Feb 8;76(3):e487-e490. doi: 10.1093/cid/ciac722.
Related Links
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Recommendations related to contraception and pregnancy testing in clinical trials
European Medicines Agency Assessment Report for Paxlovid
Information related to Paxlovid
Other Identifiers
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2022-003855-32
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
KI-PROLIFIC-2023
Identifier Type: -
Identifier Source: org_study_id