Clinical trial NCT05445674: Plasma Exchange Therapy for Post- COVID-19 Condition: A Pilot, Randomized Double-Blind Study
Official title: Plasma Exchange Therapy for Post- COVID-19 Condition: A Pilot, Randomized Double-Blind Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Post-COVID19 Condition
Keywords: SARS-CoV-2
COVID-19
Long COVID19
Plasma exchange (PE)
Plasmapheresis
Lead sponsor: Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia
Sponsor class: OTHER
Collaborators: name: IrsiCaixa
name: Banc de Sang i Teixits
First posted: 2022-07-06
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective, randomized (1:1), double-blind, placebo-controlled study
Primary purpose: TREATMENT

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.

Eligibility criteria: 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. Exclusion criteria

Exclusion Criteria:

1. SARS-CoV-2 infection diagnosed during the previous 90 days.
2. Last SARS-CoV-2 vaccine dose during the previous 30 days.
3. No significant limitations in the subject's ability to perform all usual duties/activities (i.e., grades 0, 1 or 2 in PCFS scale).
4. 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).
5. Pregnant or breastfeeding women.
6. 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.
7. Current or planned hospital admission for any cause during the study follow-up.
8. Inability to consent and/or comply with study requirements, in the opinion of the investigator.
9. Currently participating or planning to participate in any other clinical trial until day 90 of follow-up.

Primary outcomes:
measure: Evaluate the safety and tolerability of PE in patients with Post-Acute Covid-19 Syndrome (PCC) comparing to sham plasma exchange (placebo)
timeFrame: Within 90 days from the treatment start
measure: Proportion of subjects with Grade 0, 1 o 2 functional disability assessed by the functional status scale (PCFS)
timeFrame: From baseline to day 90
measure: Proportion of subjects with Grade 0, 1 o 2 functional disability assessed by the fatigue severity scale (FSS)
timeFrame: From baseline to day 90
Secondary outcomes:
measure: Assess the ability of PE to improve PCC symptoms
timeFrame: At days 0, 8, 15, 22, 45 and 90
measure: Assess the impact of PE on quality of life in subjects with PCC
timeFrame: At day 0, 8, 15, 22, 45 and 90.
measure: Assess the impact of PE on quality of life in subjects with PCC using MOS-HIV questionnaire
timeFrame: At day 0, 8, 15, 22, 45 and 90.
measure: Assess the impact of PE on neurocognitive symptoms in subjects with PCC using NeuScreen fluency Test
timeFrame: At days 0, 22 and 90
measure: Assess the impact of PE on neurocognitive symptoms in subjects with PCC using MEF-30 questionnaire
timeFrame: At days 0, 22 and 90
measure: Assess the impact of PE on neurocognitive symptoms in subjects with PCC using HADs questionnaire
timeFrame: At days 0, 22 and 90
measure: Changes in cellular anti-SARS-CoV-2 immunity associated with PE in subjects with PCC by the determination of SARS-CoV-2 specific igG
timeFrame: At day 0, 8, 15, 22, 45 and 90.
measure: Changes in cellular anti-SARS-CoV-2 immunity associated with PE in subjects with PCC by the neutralization activity evaluation
timeFrame: At day 0, 8, 15, 22, 45 and 90.
measure: Changes in cellular anti-SARS-CoV-2 immunity associated with PE in subjects with PCC by the T-Cell response
timeFrame: At day 0, 8, 15, 22, 45 and 90.
measure: Determination of residual SARS-CoV-2 particles (RNA) in plasma from subjects with PCC
timeFrame: At days 0, 8, 15, 22, 45, and 90
measure: Changes in microbiota associated with PE in subjects with PCC
timeFrame: At day 1, 8, 15, 22, 45 and 90
Other outcomes:
Locations:
city: Badalona
country: Spain
facility: Germans Trias i Pujol Hospital
state: Barcelona
Study officials:
affiliation: Germans Trias i Pujol Hospital
name: Lourdes Mateu Pruñonosa, PhD, MD
role: PRINCIPAL_INVESTIGATOR
References: