PROLIFIC - A post-acute COVID syndrome study

An Interventional, Double-Blinded, 2-Arm Study to Investigate the Efficacy of Orally Administered Nirmatrelvir/Ritonavir Compared With Placebo/Ritanovir in Non-hospitalized Adult Participants suffering from post-COVID

Status

Active, not recruiting

Phases

Phase 2

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2022-003855-32-SE

Enrollment

400

Registered

2023-01-31

Start date

2023-03-30

Completion date

Unknown

Last updated

2025-01-07

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Patients with Post-Acute COVID syndrome (PACS) in which extensive clinical and biochemical examinations have been performed. PACS patients experience a wide variety of symptoms related to physical and cognitive function, including fatigue, dyspnea, “brain fog” or other cognitive symptoms, pain, depression, and gastrointestinal issues which significantly impact quality of life. MedDRA version: 20.1 Level: HLT Classification code 10047483 Term: Viral upper respiratory tract infections System Org

Interventions

Product Name: PAXLOVID Pharmaceutical Form: Film-coated tablet INN or Proposed INN: Nirmatrelvir CAS Number: 2628280-40-8 Concentration unit: mg milligram(s) Concentration number: 600- INN or Proposed

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: Patients, =18 years of age, diagnosed with post-acute COVID-19 syndrome, with reported EQ-5D-5L VAS=65 years) yes F.1.3.1 Number of subjects for this age range 50

Exclusion criteria

Exclusion criteria: Acute COVID-19 infection, other non-related conditions with post-acute COVID-19 syndrome like symptoms, previous treatment with Paxlovid

Design outcomes

Primary

Measure	Time frame
Main Objective: To evaluate the efficacy of nirmatrelvir/ritonavir compared with that of placebo/ritonavir in patients with post-COVID-19 symptoms;Secondary Objective: To determine if nirmatrelvir/ritonavir improves secondary outcomes and selected biomarkers compared with placebo/ritonavir.;Primary end point(s): Change from baseline on the EQD5D functional scale at day 16, following a 15-day nirmatrelvir/ritonavir dosing regimen. ;Timepoint(s) of evaluation of this end point: Day 16	—

Measure

Time frame

Main Objective: To evaluate the efficacy of nirmatrelvir/ritonavir compared with that of placebo/ritonavir in patients with post-COVID-19 symptoms;Secondary Objective: To determine if nirmatrelvir/ritonavir improves secondary outcomes and selected biomarkers compared with placebo/ritonavir.;Primary end point(s): Change from baseline on the EQD5D functional scale at day 16, following a 15-day nirmatrelvir/ritonavir dosing regimen. ;Timepoint(s) of evaluation of this end point: Day 16

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Secondary

Measure	Time frame
Secondary end point(s): • To assess the effect of the study drug on Quality of Life compared to baseline. • To test the hypothesis that the study drug: • improves the hemodynamic response to active standing test defined as a reduction in delta maximum heart rate during standing (only patients diagnosed with POTS) compared to baseline. • improves reactive hyperemia index compared to baseline. • reduces 24-h average heart rate compared to baseline. • reduces persistent fever compared to baseline. • improves physical capacity compared to baseline. • improves handgrip strength compared to baseline. • improves physical activity compared to baseline. • drug reduces post exertional malaise compared to baseline. • reduces fatigue compared to baseline. • reduces cognitive dysfunction compared to baseline. • reduces dyspnea compared to baseline. • reduces dysfunctional breathing patterns including reduced maximum inspiratory pressure and lung function compared to baseline. • reduces inflammatory biomarkers (increased D-dimer, CRP, ESR, ferritin, NT-proBNP, LD) • improves dysautonomia symptoms compared to baseline ;Timepoint(s) of evaluation of this end point: Up to 90 days	—

Measure

Time frame

Secondary end point(s): • To assess the effect of the study drug on Quality of Life compared to baseline. • To test the hypothesis that the study drug: • improves the hemodynamic response to active standing test defined as a reduction in delta maximum heart rate during standing (only patients diagnosed with POTS) compared to baseline. • improves reactive hyperemia index compared to baseline. • reduces 24-h average heart rate compared to baseline. • reduces persistent fever compared to baseline. • improves physical capacity compared to baseline. • improves handgrip strength compared to baseline. • improves physical activity compared to baseline. • drug reduces post exertional malaise compared to baseline. • reduces fatigue compared to baseline. • reduces cognitive dysfunction compared to baseline. • reduces dyspnea compared to baseline. • reduces dysfunctional breathing patterns including reduced maximum inspiratory pressure and lung function compared to baseline. • reduces inflammatory biomarkers (increased D-dimer, CRP, ESR, ferritin, NT-proBNP, LD) • improves dysautonomia symptoms compared to baseline ;Timepoint(s) of evaluation of this end point: Up to 90 days

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Countries

Sweden

Contacts

Public ContactAnders Mälarstig

Karolinska Institutet

anders.malarstig@ki.se46768892514

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026