Post-COVID19 ConditionPhase 2NCT05445674
Plasma Exchange Therapy for Post- COVID-19 Condition: A Pilot, Randomized Double-Blind Study
A Phase 2 study testing Plasma Exchange Procedure in people with Post-COVID19 Condition, run by Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia at 1 site in Spain.
Trial summary
PAX is a prospective, randomized (1:1), double-blind, placebo-controlled study, that have as a objective to evaluate the safety and tolerability of plasma exchange (PE) in patients with Post Acute Covid-19 Syndrome (PCC) comparing to sham plasma exchange. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Post-COVID19 Condition
- What is being tested?
- Plasma Exchange Procedure
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteSpain
- Study dates
- 22 Sep 2022to 6 Jun 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female individuals 18 years-old or older.
- Evidence of previous SARS-CoV-2 infection at least 90 days prior to study recruitment, defined by either (a) Nasopharyngeal SARS-CoV-2 nucleic acid test (Polymerase chain reaction [PCR] or Transcription-Mediated Amplification [TMA] (b) validated Nasopharyngeal Lateral Flow Assay rapid antigen test [RAT], or (c) SARSCoV-2 serology before SARS-CoV-2 vaccination.
- Symptoms of PCC after 90 days of infection and that last for at least 2 months and cannot explained by an alternative diagnosis.
- Not able to perform all usual duties/ activities due to symptoms, pain, depression or anxiety, defined as grades 3 or 4 in the post-COVID-19 Functional Status (PCFS) scale.
- Availability of an adequate peripheral venous cannulation.
- If women of childbearing potential, use of a highly effective method of contraception (abstinence, hormonal contraception, intra-uterine device [IUD], or anatomical sterility in self).
- Willing to comply with the requirements of the protocol and available for followup for the planned duration of the study.
- Has understood the information provided and capable of giving informed consent. Exclusion criteria
Who cannot join
- SARS-CoV-2 infection diagnosed during the previous 90 days.
- Last SARS-CoV-2 vaccine dose during the previous 30 days.
- No significant limitations in the subject's ability to perform all usual duties/activities (i.e., grades 0, 1 or 2 in PCFS scale).
- Medical conditions for which 250 mL of intravenous fluid is considered dangerous (i.e., decompensated heart failure or renal failure with fluid overload, among others).
- Pregnant or breastfeeding women.
- Contraindications for therapeutic PE: Non-availability of an adequate peripheral venous catheter, hemodynamic instability, septicemia, known allergy to fresh frozen plasma or replacement colloid/albumin, known allergy to heparin.
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- Current or planned hospital admission for any cause during the study follow-up.
- Inability to consent and/or comply with study requirements, in the opinion of the investigator.
- Currently participating or planning to participate in any other clinical trial until day 90 of follow-up.
Trial locations and contacts
1 site in 1 country.
About this study
PAX is a prospective, randomized (1:1), double-blind, placebo-controlled study, that have as a objective to evaluate the safety and tolerability of plasma exchange (PE) in patients with Post Acute Covid-19 Syndrome (PCC) comparing to sham plasma exchange. The participants will be randomized in two arms: (1) 6 sessions of PE (Plasma Exchange) with human serum albumin 5% or (2) 6 sessions with placebo (infusion of of sterile saline solution 0.9%) on days 1, 3, 8, 10, 15 and 17.
Read the detailed description
Randomized participants will receive plasma exchange (PE) or sham PE (placebo) (6 sessions: V2, V3, V4, V5, V6 and V7) and will continue their follow-up visits(V8d22, V9d45, V10d90). Plasma volumes will be replaced, which will vary depending on sex, height, weight and hematocrit.
- Conditions
- Post-COVID19 Condition
- Being tested
- Plasma Exchange Procedure, Sham Plasma Exchange Procedure
- Keywords
- SARS-CoV-2, COVID-19, Long COVID19, Plasma exchange (PE), Plasmapheresis
- Medical subject headings
- COVID-19, Post-Acute COVID-19 Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Plasma Exchange ProcedureCombination product
Also called Plasmapheresis
Plasma exchanges will be performed with 5% albumin as the replacement fluid. The typical schedule prescribed will be an exchange of 1 volemia. Blood will be separated into cells and plasma; the cells will be combined with reconstituted 5% human serum albumin and reinfused into the patient with normal saline
Sham Plasma Exchange ProcedureOther
For sham plasma exchange procedures, a sound behind the curtain will be performed imitating the sound of the cell processing platform. In these cases, only one infusion of 200 to 250ml of sterile saline solution 0.9% will be performed during the time stablished for all procedures. Albumin will not be necessary for those patients in the Sham plasma exchange arm
| Study group | Role | What they receive |
|---|---|---|
| Plasma Exchange | Experimental | 6 sessions of PE with human serum 5% albumin. Plasma exchange sessions will occur on days 1, 3, 8, 10, 15 and 17 Receives: Combination Product: Plasma Exchange Procedure |
| Sham Plasma Exchange | Sham comparator | 6 sessions of sham plasma exchange (one infusion of sterile saline solution 0.9%) on days 1, 3, 8, 10, 15 and 17. Receives: Other: Sham Plasma Exchange Procedure |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluate the safety and tolerability of PE in patients with Post-Acute Covid-19 Syndrome (PCC) comparing to sham plasma exchange (placebo)
Proportion of adverse events (AEs) through day 90, considering:
- All AEs
- Grade 3 and 4 AEs
- AEs leading to study discontinuation
Measured: Within 90 days from the treatment start
Proportion of subjects with Grade 0, 1 o 2 functional disability assessed by the functional status scale (PCFS)
Grade 0, 1 o 2 functional disability assessed by the functional status scale (PCFS), being 0 the better outcome and 4 the worse outcome
Measured: From baseline to day 90
Proportion of subjects with Grade 0, 1 o 2 functional disability assessed by the fatigue severity scale (FSS)
Grade 0, 1 o 2 functional disability assessed by the fatigue severity scale (FSS), being 1 the better outcome and 70 the worse outcome
Measured: From baseline to day 90
Secondary outcomes (11)
Assess the ability of PE to improve PCC symptoms
Can Ruti PCC symptoms scale questionnare by days 0, 8, 15, 22, 45 and 90
Measured: At days 0, 8, 15, 22, 45 and 90
Assess the impact of PE on quality of life in subjects with PCC
Quality of life questionnaires: EuroQol-5D questionnaire being 5 the better outcome and 15 the worse outcome.
Measured: At day 0, 8, 15, 22, 45 and 90.
Assess the impact of PE on quality of life in subjects with PCC using MOS-HIV questionnaire
Quality of life questionnaires: MOS-HIV questionnaire being 4 the better outcome and 1 the worse outcome.
Measured: At day 0, 8, 15, 22, 45 and 90.
Assess the impact of PE on neurocognitive symptoms in subjects with PCC using NeuScreen fluency Test
The neurocognitive evaluation assessed by the NeuScreen fluency test (Seconds)
Measured: At days 0, 22 and 90
Assess the impact of PE on neurocognitive symptoms in subjects with PCC using MEF-30 questionnaire
The neurocognitive evaluation assessed by the MEF-30 questionnaire, with being 0 the better outcome and 120 being the worse outcome.
Measured: At days 0, 22 and 90
Assess the impact of PE on neurocognitive symptoms in subjects with PCC using HADs questionnaire
The neurocognitive evaluation assessed by the HADs questionnaire, with being 0 as the better outcome and 21 being the worse outcome.
Measured: At days 0, 22 and 90
Changes in cellular anti-SARS-CoV-2 immunity associated with PE in subjects with PCC by the determination of SARS-CoV-2 specific igG
Changes in cellular anti-SARS-CoV-2 immunity associated with PE in subjects with PCC by the determination of SARS-CoV-2 specific igG in plasma (Arbitrary Units, AU)
Measured: At day 0, 8, 15, 22, 45 and 90.
Changes in cellular anti-SARS-CoV-2 immunity associated with PE in subjects with PCC by the neutralization activity evaluation
Changes in cellular anti-SARS-CoV-2 immunity associated with PE in subjects with PCC by the analysis of reciprocal titers of neutralizing antibodies against SARS-CoV-2
Measured: At day 0, 8, 15, 22, 45 and 90.
Changes in cellular anti-SARS-CoV-2 immunity associated with PE in subjects with PCC by the T-Cell response
Changes in cellular anti-SARS-CoV-2 immunity associated with PE in subjects with PCC by the reduction of T-Cell response (%) from plasma samples
Measured: At day 0, 8, 15, 22, 45 and 90.
Determination of residual SARS-CoV-2 particles (RNA) in plasma from subjects with PCC
Virological assessment to determine the residual SARS-CoV-2 RNA (copies/mL)
Measured: At days 0, 8, 15, 22, 45, and 90
Changes in microbiota associated with PE in subjects with PCC
Stool assessment to determine the residual SARS-CoV-2 RNA (copies/mL)
Measured: At day 1, 8, 15, 22, 45 and 90
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jul 2022
- Study start22 Sep 2022
- Primary completion6 Jun 2023
- Study completion6 Jun 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Post-COVID19 ConditionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Prospective, randomized (1:1), double-blind, placebo-controlled study
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia
- Sponsor type
- University, hospital or other
- Collaborators
- IrsiCaixa, Banc de Sang i Teixits
- Responsible party
- Sponsor
- Investigators
- Lourdes Mateu Pruñonosa, PhD, MD, Principal investigator, Germans Trias i Pujol Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05445674
- Sponsor's protocol ID
- PAX
- Status last verified
- Jun 2023
- First submitted
- 27 Jun 2022
- Last updated
- 7 Jun 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Espana-Cueto S, Loste C, Llados G, Lopez C, Santos JR, Dulsat G, Garcia A, Carmezim J, Carabia J, Ancochea A, Fernandez-Prendres C, Morales-Indiano C, Quirant B, Martinez-Caceres E, Sanchez A, Parraga IG, Chamorro A, San Jose A, Abad E, Munoz-Moreno JA, Prats A, Fumaz CR, Coll-Fernandez R, Estany C, Torrano P, Puig J, Clotet B, Tebe C, Massanella M, Paredes R, Mateu L. Plasma exchange therapy for the post COVID-19 condition: a phase II, double-blind, placebo-controlled, randomized trial. Nat Commun. 2025 Feb 24;16(1):1929. doi: 10.1038/s41467-025-57198-7.
PubMed 39994269
Study at a glance
From the registry record, last updated by the sponsor on 7 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Plasma Exchange Therapy for Post- COVID-19 Condition: A Pilot, Randomized Double-Blind Study
- ClinicalTrials.gov ID
- NCT05445674
- Acronym / sponsor ID
- PAX
- Conditions
- Post-COVID19 Condition
- Keywords
- SARS-CoV-2, COVID-19, Long COVID19, Plasma exchange (PE), Plasmapheresis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la CienciaUniversity, hospital or other
- Collaborators
- IrsiCaixa, Banc de Sang i Teixits
- Study start
- 22 Sep 2022 (actual)
- Primary completion
- 6 Jun 2023 (actual)
- Study completion
- 6 Jun 2023 (actual)
- First posted
- 6 Jul 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
PAX is a prospective, randomized (1:1), double-blind, placebo-controlled study, that have as a objective to evaluate the safety and tolerability of plasma exchange (PE) in patients with Post Acute Covid-19 Syndrome (PCC) comparing to sham plasma exchange. The participants will be randomized in two arms: (1) 6 sessions of PE (Plasma Exchange) with human serum albumin 5% or (2) 6 sessions with placebo (infusion of of sterile saline solution 0.9%) on days 1, 3, 8, 10, 15 and 17.
Detailed description
Randomized participants will receive plasma exchange (PE) or sham PE (placebo) (6 sessions: V2, V3, V4, V5, V6 and V7) and will continue their follow-up visits(V8d22, V9d45, V10d90). Plasma volumes will be replaced, which will vary depending on sex, height, weight and hematocrit.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- Prospective, randomized (1:1), double-blind, placebo-controlled study
| Arm | Type | Receives |
|---|---|---|
| Plasma Exchange | Experimental | Combination Product: Plasma Exchange Procedure6 sessions of PE with human serum 5% albumin. Plasma exchange sessions will occur on days 1, 3, 8, 10, 15 and 17 |
| Sham Plasma Exchange | Sham comparator | Other: Sham Plasma Exchange Procedure6 sessions of sham plasma exchange (one infusion of sterile saline solution 0.9%) on days 1, 3, 8, 10, 15 and 17. |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Male or female individuals 18 years-old or older.
- Evidence of previous SARS-CoV-2 infection at least 90 days prior to study recruitment, defined by either (a) Nasopharyngeal SARS-CoV-2 nucleic acid test (Polymerase chain reaction [PCR] or Transcription-Mediated Amplification [TMA] (b) validated Nasopharyngeal Lateral Flow Assay rapid antigen test [RAT], or (c) SARSCoV-2 serology before SARS-CoV-2 vaccination.
- Symptoms of PCC after 90 days of infection and that last for at least 2 months and cannot explained by an alternative diagnosis.
- Not able to perform all usual duties/ activities due to symptoms, pain, depression or anxiety, defined as grades 3 or 4 in the post-COVID-19 Functional Status (PCFS) scale.
- Availability of an adequate peripheral venous cannulation.
Key exclusion criteria (9 listed)
- SARS-CoV-2 infection diagnosed during the previous 90 days.
- Last SARS-CoV-2 vaccine dose during the previous 30 days.
- No significant limitations in the subject's ability to perform all usual duties/activities (i.e., grades 0, 1 or 2 in PCFS scale).
- Medical conditions for which 250 mL of intravenous fluid is considered dangerous (i.e., decompensated heart failure or renal failure with fluid overload, among others).
- Pregnant or breastfeeding women.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Plasma Exchange ProcedureAlso: PlasmapheresisPlasma exchanges will be performed with 5% albumin as the replacement fluid. The typical schedule prescribed will be an exchange of 1 volemia. Blood will be separated into cells and plasma; the cells will be combined with reconstituted 5% human serum albumin and reinfused into the patient with normal saline | Combination product | Plasma Exchange |
| Sham Plasma Exchange ProcedureFor sham plasma exchange procedures, a sound behind the curtain will be performed imitating the sound of the cell processing platform. In these cases, only one infusion of 200 to 250ml of sterile saline solution 0.9% will be performed during the time stablished for all procedures. Albumin will not be necessary for those patients in the Sham plasma exchange arm | Other | Sham Plasma Exchange |
Primary outcome
Evaluate the safety and tolerability of PE in patients with Post-Acute Covid-19 Syndrome (PCC) comparing to sham plasma exchange (placebo)
Time frame: Within 90 days from the treatment start
Proportion of adverse events (AEs) through day 90, considering: * All AEs * Grade 3 and 4 AEs * AEs leading to study discontinuation
Proportion of subjects with Grade 0, 1 o 2 functional disability assessed by the functional status scale (PCFS)
Time frame: From baseline to day 90
Grade 0, 1 o 2 functional disability assessed by the functional status scale (PCFS), being 0 the better outcome and 4 the worse outcome
Proportion of subjects with Grade 0, 1 o 2 functional disability assessed by the fatigue severity scale (FSS)
Time frame: From baseline to day 90
Grade 0, 1 o 2 functional disability assessed by the fatigue severity scale (FSS), being 1 the better outcome and 70 the worse outcome
11 secondary outcomes
Assess the ability of PE to improve PCC symptoms
Time frame: At days 0, 8, 15, 22, 45 and 90
Assess the impact of PE on quality of life in subjects with PCC
Time frame: At day 0, 8, 15, 22, 45 and 90.
Assess the impact of PE on quality of life in subjects with PCC using MOS-HIV questionnaire
Time frame: At day 0, 8, 15, 22, 45 and 90.
Assess the impact of PE on neurocognitive symptoms in subjects with PCC using NeuScreen fluency Test
Time frame: At days 0, 22 and 90
Assess the impact of PE on neurocognitive symptoms in subjects with PCC using MEF-30 questionnaire
Time frame: At days 0, 22 and 90
Assess the impact of PE on neurocognitive symptoms in subjects with PCC using HADs questionnaire
Time frame: At days 0, 22 and 90
Changes in cellular anti-SARS-CoV-2 immunity associated with PE in subjects with PCC by the determination of SARS-CoV-2 specific igG
Time frame: At day 0, 8, 15, 22, 45 and 90.
Changes in cellular anti-SARS-CoV-2 immunity associated with PE in subjects with PCC by the neutralization activity evaluation
Time frame: At day 0, 8, 15, 22, 45 and 90.
Changes in cellular anti-SARS-CoV-2 immunity associated with PE in subjects with PCC by the T-Cell response
Time frame: At day 0, 8, 15, 22, 45 and 90.
Determination of residual SARS-CoV-2 particles (RNA) in plasma from subjects with PCC
Time frame: At days 0, 8, 15, 22, 45, and 90
Changes in microbiota associated with PE in subjects with PCC
Time frame: At day 1, 8, 15, 22, 45 and 90
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jun 2023.
- Derived from this study: PubMed 39994269Espana-Cueto S, Loste C, Llados G, Lopez C, Santos JR, Dulsat G, Garcia A, Carmezim J, Carabia J, Ancochea A, Fernandez-Prendres C, Morales-Indiano C, Quirant B, Martinez-Caceres E, Sanchez A, Parraga IG, Chamorro A, San Jose A, Abad E, Munoz-Moreno JA, Prats A, Fumaz CR, Coll-Fernandez R, Estany C, Torrano P, Puig J, Clotet B, Tebe C, Massanella M, Paredes R, Mateu L. Plasma exchange therapy for the post COVID-19 condition: a phase II, double-blind, placebo-controlled, randomized trial. Nat Commun. 2025 Feb 24;16(1):1929. doi: 10.1038/s41467-025-57198-7.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lourdes Mateu Pruñonosa, PhD, MD principal investigator
Germans Trias i Pujol Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Plasma Exchange Procedure in people with Post-COVID19 Condition, run by Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Evaluate the safety and tolerability of PE in patients with Post-Acute Covid-19 Syndrome (PCC) comparing to sham plasma exchange (placebo) (time frame: Within 90 days from the treatment start). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05445674, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jun 2023.