Back to results

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

Primary Purpose

Post-COVID19 Condition

Status

Completed

Phase

Phase 2

Locations

Spain

Study Type

Interventional

Intervention

Plasma Exchange Procedure

Sham Plasma Exchange Procedure

About this trial

This is an interventional treatment trial for Post-COVID19 Condition focused on measuring SARS-CoV-2, COVID-19, Long COVID19, Plasma exchange (PE), Plasmapheresis

Eligibility Criteria

18 Years - 100 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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.
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.

Sites / Locations

Germans Trias i Pujol Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Sham Comparator

Arm Label

Plasma Exchange

Sham Plasma Exchange

Arm Description

6 sessions of PE with human serum 5% albumin. Plasma exchange sessions will occur on days 1, 3, 8, 10, 15 and 17

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

Outcomes

Primary Outcome Measures

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

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

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

Secondary Outcome Measures

Assess the ability of PE to improve PCC symptoms

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

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

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

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

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

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 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)

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

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

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)

Changes in microbiota associated with PE in subjects with PCC

Stool assessment to determine the residual SARS-CoV-2 RNA (copies/mL)

Full Information

NCT ID

NCT05445674

First Posted

June 27, 2022

Last Updated

June 6, 2023

Sponsor

Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia

Collaborators

IrsiCaixa, Banc de Sang i Teixits

1. Study Identification

Unique Protocol Identification Number

NCT05445674

Brief Title

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

2. Study Status

Record Verification Date

June 2023

Overall Recruitment Status

Completed

Study Start Date

September 22, 2022 (Actual)

Primary Completion Date

June 6, 2023 (Actual)

Study Completion Date

June 6, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia

Collaborators

IrsiCaixa, Banc de Sang i Teixits

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Post-COVID19 Condition

Keywords

SARS-CoV-2, COVID-19, Long COVID19, Plasma exchange (PE), Plasmapheresis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Model Description

Prospective, randomized (1:1), double-blind, placebo-controlled study

Masking

ParticipantInvestigator

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

Allocation

Randomized

Enrollment

50 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Plasma Exchange

Arm Type

Experimental

Arm Description

6 sessions of PE with human serum 5% albumin. Plasma exchange sessions will occur on days 1, 3, 8, 10, 15 and 17

Arm Title

Sham Plasma Exchange

Arm Type

Sham Comparator

Arm Description

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

Intervention Type

Combination Product

Intervention Name(s)

Plasma Exchange Procedure

Other Intervention Name(s)

Plasmapheresis

Intervention Description

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

Intervention Type

Other

Intervention Name(s)

Sham Plasma Exchange Procedure

Intervention Description

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

Primary Outcome Measure Information:

Title

Evaluate the safety and tolerability of PE in patients with Post-Acute Covid-19 Syndrome (PCC) comparing to sham plasma exchange (placebo)

Description

Proportion of adverse events (AEs) through day 90, considering: All AEs Grade 3 and 4 AEs AEs leading to study discontinuation

Time Frame

Within 90 days from the treatment start

Title

Proportion of subjects with Grade 0, 1 o 2 functional disability assessed by the functional status scale (PCFS)

Description

Grade 0, 1 o 2 functional disability assessed by the functional status scale (PCFS), being 0 the better outcome and 4 the worse outcome

Time Frame

From baseline to day 90

Title

Proportion of subjects with Grade 0, 1 o 2 functional disability assessed by the fatigue severity scale (FSS)

Description

Grade 0, 1 o 2 functional disability assessed by the fatigue severity scale (FSS), being 1 the better outcome and 70 the worse outcome

Time Frame

From baseline to day 90

Secondary Outcome Measure Information:

Title

Assess the ability of PE to improve PCC symptoms

Description

Can Ruti PCC symptoms scale questionnare by days 0, 8, 15, 22, 45 and 90

Time Frame

At days 0, 8, 15, 22, 45 and 90

Title

Assess the impact of PE on quality of life in subjects with PCC

Description

Quality of life questionnaires: EuroQol-5D questionnaire being 5 the better outcome and 15 the worse outcome.

Time Frame

At day 0, 8, 15, 22, 45 and 90.

Title

Assess the impact of PE on quality of life in subjects with PCC using MOS-HIV questionnaire

Description

Quality of life questionnaires: MOS-HIV questionnaire being 4 the better outcome and 1 the worse outcome.

Time Frame

At day 0, 8, 15, 22, 45 and 90.

Title

Assess the impact of PE on neurocognitive symptoms in subjects with PCC using NeuScreen fluency Test

Description

The neurocognitive evaluation assessed by the NeuScreen fluency test (Seconds)

Time Frame

At days 0, 22 and 90

Title

Assess the impact of PE on neurocognitive symptoms in subjects with PCC using MEF-30 questionnaire

Description

The neurocognitive evaluation assessed by the MEF-30 questionnaire, with being 0 the better outcome and 120 being the worse outcome.

Time Frame

At days 0, 22 and 90

Title

Assess the impact of PE on neurocognitive symptoms in subjects with PCC using HADs questionnaire

Description

The neurocognitive evaluation assessed by the HADs questionnaire, with being 0 as the better outcome and 21 being the worse outcome.

Time Frame

At days 0, 22 and 90

Title

Changes in cellular anti-SARS-CoV-2 immunity associated with PE in subjects with PCC by the determination of SARS-CoV-2 specific igG

Description

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)

Time Frame

At day 0, 8, 15, 22, 45 and 90.

Title

Changes in cellular anti-SARS-CoV-2 immunity associated with PE in subjects with PCC by the neutralization activity evaluation

Description

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

Time Frame

At day 0, 8, 15, 22, 45 and 90.

Title

Changes in cellular anti-SARS-CoV-2 immunity associated with PE in subjects with PCC by the T-Cell response

Description

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

Time Frame

At day 0, 8, 15, 22, 45 and 90.

Title

Determination of residual SARS-CoV-2 particles (RNA) in plasma from subjects with PCC

Description

Virological assessment to determine the residual SARS-CoV-2 RNA (copies/mL)

Time Frame

At days 0, 8, 15, 22, 45, and 90

Title

Changes in microbiota associated with PE in subjects with PCC

Description

Stool assessment to determine the residual SARS-CoV-2 RNA (copies/mL)

Time Frame

At day 1, 8, 15, 22, 45 and 90

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

100 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 Exclusion Criteria: 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. 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Lourdes Mateu Pruñonosa, PhD, MD

Organizational Affiliation

Germans Trias i Pujol Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Germans Trias i Pujol Hospital

City

Badalona

State/Province

Barcelona

ZIP/Postal Code

08916

Country

Spain

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs