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

Study Overview

• Status: Completed
• Conditions: Post-COVID19 Condition
• Intervention / Treatment: Combination product: Plasma Exchange Procedure; Other: Sham Plasma Exchange Procedure

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 Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• Spain
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Germans Trias i Pujol Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Plasma Exchange; 6 sessions of PE with human serum 5% albumin. Plasma exchange sessions will occur on days 1, 3, 8, 10, 15 and 17	Combination product: Plasma 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; Other Names: Plasmapheresis
Sham Comparator: Sham Plasma Exchange; 6 sessions of sham plasma exchange (one infusion of sterile saline solution 0.9%) on days 1, 3, 8, 10, 15 and 17.	Other: Sham 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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	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	From baseline to day 90

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess the ability of PE to improve PCC symptoms	Can Ruti PCC symptoms scale questionnare by days 0, 8, 15, 22, 45 and 90	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.	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.	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)	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.	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.	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)	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	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	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)	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)	At day 1, 8, 15, 22, 45 and 90

Collaborators and Investigators

• Sponsor: Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia
• Collaborators: Banc de Sang i Teixits; IrsiCaixa
• Investigators: Principal Investigator: Lourdes Mateu Pruñonosa, PhD, MD, Germans Trias i Pujol Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 22, 2022
• Primary Completion (Actual): June 6, 2023
• Study Completion (Actual): June 6, 2023

Study Registration Dates

• First Submitted: June 27, 2022
• First Submitted That Met QC Criteria: July 5, 2022
• First Posted (Actual): July 6, 2022

Study Record Updates

• Last Update Posted (Actual): June 7, 2023
• Last Update Submitted That Met QC Criteria: June 6, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: SARS-CoV-2; COVID-19; Plasmapheresis; Plasma exchange (PE); Long COVID19
• Additional Relevant MeSH Terms: Pathologic Processes; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Disease
• Other Study ID Numbers: PAX

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No