Plasma Exchange Therapy for Post- COVID-19 Condition: A Pilot, Randomized Double-Blind Study

Phase 2

Completed

• Conditions: Post-COVID19 Condition
• Interventions: Combination Product: Plasma Exchange Procedure; Other: Sham Plasma Exchange Procedure

• Registration Number: NCT05445674
• Lead Sponsor: Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia

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.

Study Timeline

• Study First Submitted: 2022-06-27
• Study First Submitted QC: 2022-07-05
• Study First Posted: 2022-07-06
• Study Start: 2022-09-22
• Status Verified: 2023-06
• Primary Completion: 2023-06-06
• Study Completion: 2023-06-06
• Last Update Submitted: 2023-06-06
• Last Update Posted: 2023-06-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 50

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Plasma Exchange	Plasma Exchange Procedure	6 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 Plasma Exchange Procedure	6 sessions of sham plasma exchange (one infusion of sterile saline solution 0.9%) on days 1, 3, 8, 10, 15 and 17.

Primary Outcome Measures

Name	Time	Method
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
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 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 Outcome Measures

Name	Time	Method
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
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.
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 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)
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.
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.
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
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 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)

Trial Locations

Locations (1)

Germans Trias i Pujol Hospital; 🇪🇸 Badalona, Barcelona, Spain