Post-COVID19 Condition
Conditions
Keywords
SARS-CoV-2, COVID-19, Long COVID19, Plasma exchange (PE), Plasmapheresis
Brief 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. 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.
Interventions
COMBINATION_PRODUCTPlasma Exchange Procedure
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
OTHERSham Plasma Exchange Procedure
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
Sponsors
IrsiCaixa
Banc de Sang i Teixits
Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
This will be a double blind, placebo-controlled study. Masking of investigational products will ensure that both the investigator and the participant are blinded to the type of exchange procedure. Patients will be unable to distinguish true from sham procedures at the end of the study. Each procedure will take approximately 2 hours to complete. In the sham procedure, the patients will also underwear 6 procedures lasting approximately 2 hours each. Blinding will be maintained throughout the study until after 3-month follow-up assessment of the last patient exchanged
Intervention model description
Prospective, randomized (1:1), double-blind, placebo-controlled study
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female individuals 18 years-old or older. 2. 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. 3. Symptoms of PCC after 90 days of infection and that last for at least 2 months and cannot explained by an alternative diagnosis. 4. 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. 5. Availability of an adequate peripheral venous cannulation. 6. 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). 7. Willing to comply with the requirements of the protocol and available for followup for the planned duration of the study. 8. Has understood the information provided and capable of giving informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate the safety and tolerability of PE in patients with Post-Acute Covid-19 Syndrome (PCC) comparing to sham plasma exchange (placebo) | 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) | 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) | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Assess the impact of PE on quality of life in subjects with PCC | At day 0, 8, 15, 22, 45 and 90. | Quality of life questionnaires: EuroQol-5D questionnaire being 5 the better outcome and 15 the worse outcome. |
| Assess the impact of PE on quality of life in subjects with PCC using MOS-HIV questionnaire | At day 0, 8, 15, 22, 45 and 90. | Quality of life questionnaires: MOS-HIV questionnaire being 4 the better outcome and 1 the worse outcome. |
| Assess the impact of PE on neurocognitive symptoms in subjects with PCC using NeuScreen fluency Test | At days 0, 22 and 90 | The neurocognitive evaluation assessed by the NeuScreen fluency test (Seconds) |
| Changes in cellular anti-SARS-CoV-2 immunity associated with PE in subjects with PCC by the determination of SARS-CoV-2 specific igG | 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 determination of SARS-CoV-2 specific igG in plasma (Arbitrary Units, AU) |
| Assess the impact of PE on neurocognitive symptoms in subjects with PCC using MEF-30 questionnaire | At days 0, 22 and 90 | The neurocognitive evaluation assessed by the MEF-30 questionnaire, with being 0 the better outcome and 120 being the worse outcome. |
| Changes in cellular anti-SARS-CoV-2 immunity associated with PE in subjects with PCC by the T-Cell response | 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 reduction of T-Cell response (%) from plasma samples |
| Determination of residual SARS-CoV-2 particles (RNA) in plasma from subjects with PCC | At days 0, 8, 15, 22, 45, and 90 | Virological assessment to determine the residual SARS-CoV-2 RNA (copies/mL) |
| Changes in microbiota associated with PE in subjects with PCC | At day 1, 8, 15, 22, 45 and 90 | Stool assessment to determine the residual SARS-CoV-2 RNA (copies/mL) |
| Changes in cellular anti-SARS-CoV-2 immunity associated with PE in subjects with PCC by the neutralization activity evaluation | 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 analysis of reciprocal titers of neutralizing antibodies against SARS-CoV-2 |
| Assess the impact of PE on neurocognitive symptoms in subjects with PCC using HADs questionnaire | At days 0, 22 and 90 | The neurocognitive evaluation assessed by the HADs questionnaire, with being 0 as the better outcome and 21 being the worse outcome. |
| Assess the ability of PE to improve PCC symptoms | At days 0, 8, 15, 22, 45 and 90 | Can Ruti PCC symptoms scale questionnare by days 0, 8, 15, 22, 45 and 90 |
Countries
Spain
Outcome results
None listed