Clinical Trial Results:
Plasma Exchange Therapy for Post- COVID-19 Condition: A Pilot, Randomized Double-Blind Study
Summary
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EudraCT number |
2022-000641-33 |
Trial protocol |
ES |
Global end of trial date |
15 Jun 2023
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Results information
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Results version number |
v1(current) |
This version publication date |
07 Sep 2024
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First version publication date |
07 Sep 2024
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Other versions |
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Summary report(s) |
Quality of life and laboratory Endpoints |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
PAX
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT05445674 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Fundació Lluita contra les Infeccions
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Sponsor organisation address |
Carretera de Canyet s/n, Badalona, Spain, 08916
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Public contact |
ScienHub Research Support, Fundació Lluita contra les Infeccions, 34 934978414, info@scienhub.org
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Scientific contact |
ScienHub Research Support, Fundació Lluita contra les Infeccions, 34 934978414, info@scienhub.org
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
06 Feb 2024
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
06 Jun 2023
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Global end of trial reached? |
Yes
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Global end of trial date |
15 Jun 2023
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
Evaluate the safety and tolerability of PE in patients with Post-Acute Covid-19 Syndrome (PCC) compared to sham plasma exchange (placebo).
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Protection of trial subjects |
Patients will discontinue participation in the study at the time they deem necessary. All study participants have the right to withdraw their consent at any time during the study. This event will be notified to the study monitor and duly documented both in the medical records and in the eCRF.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
22 Sep 2022
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Spain: 50
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Worldwide total number of subjects |
50
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EEA total number of subjects |
50
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
50
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Participants have been recruited from the LONG COVID-19 unit at Hospital Universitari Germans Trias i Pujol. | |||||||||||||||
Pre-assignment
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Screening details |
Adult men and women with confirmed Post-Acute COVID-19 syndrome (PCC) diagnosis (Symptoms of persistent COVID-19 after 90 days of infection, not explainable by other causes and previous diagnosis of SARS-CoV-2 infection (WHO criteria), determined by PCR, validated antigen rapid diagnostic test and or positive serology test for COVID-19 (>90 days). | |||||||||||||||
Period 1
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Period 1 title |
Overall Period
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Is this the baseline period? |
Yes | |||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst | |||||||||||||||
Blinding implementation details |
Masking of investigational products ensured that the investigator and the participant were blinded to the type of exchange procedure. Patients could not 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
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Experimental Arm | |||||||||||||||
Arm description |
6 sessions of PE (Plasma Exchange) with human serum albumin. Plasma exchange sessions will occur on days 1, 3, 8, 10, 15 and 17. | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Plasma Exchange with human serum album
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Infusion
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Routes of administration |
Infusion
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Dosage and administration details |
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. Conventional fresh-frozen plasma will be used as replacement fluid (1/3 of the exchanged plasma volume) only in patients with a baseline coagulopathy (PT <50%). The fresh-frozen plasma to be used will be provided by the Blood and Tissues Bank from Hospital Universitari Germans Trias i Pujol.
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Investigational medicinal product name |
Human albumin 5%
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Investigational medicinal product code |
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Other name |
Albutein 5% ®
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Pharmaceutical forms |
Infusion
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Routes of administration |
Infusion , Intravenous use
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Dosage and administration details |
Human albumin 5% (Albutein 5% ®), solution for intravenous infusion. It will be used in bottles of 250mL or 500mL depending on availability. The administration volume will be adapted for each participant. Solution for infusion, clear, slightly viscous. Storage conditions: Keep at 25ºC maximum. Refrigeration is not necessary under these conditions. Protect from light. Do not freeze.
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Arm title
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Placebo Arm | |||||||||||||||
Arm description |
6 sessions with placebo (infusion of 200 to 250ml of sterile saline solution 0.9%) on days 1, 3, 8, 10, 15 and 17. | |||||||||||||||
Arm type |
Placebo | |||||||||||||||
Investigational medicinal product name |
Sterile saline solution 0.9%
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Infusion
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Routes of administration |
Infusion
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Dosage and administration details |
For sham plasma exchange procedures, a sound behind the curtain was performed imitating the sound of the cell processing platform, the participant wore headphones connected to a tablet with music. In these cases, only one infusion of 200 to 250ml of sterile saline solution 0.9% will be performed during the time established for all procedures. Albumin will not be necessary for those patients in the Sham plasma exchange arm.
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Baseline characteristics reporting groups
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Reporting group title |
Experimental Arm
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Reporting group description |
6 sessions of PE (Plasma Exchange) with human serum albumin. Plasma exchange sessions will occur on days 1, 3, 8, 10, 15 and 17. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo Arm
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Reporting group description |
6 sessions with placebo (infusion of 200 to 250ml of sterile saline solution 0.9%) on days 1, 3, 8, 10, 15 and 17. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Experimental Arm
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Reporting group description |
6 sessions of PE (Plasma Exchange) with human serum albumin. Plasma exchange sessions will occur on days 1, 3, 8, 10, 15 and 17. | ||
Reporting group title |
Placebo Arm
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Reporting group description |
6 sessions with placebo (infusion of 200 to 250ml of sterile saline solution 0.9%) on days 1, 3, 8, 10, 15 and 17. |
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End point title |
Proportion of adverse events (AEs) through day 90: all AEs | ||||||||||||
End point description |
In the primary analysis, the proportions of adverse events up to day 90 were described and compared between treatment arms using a Fisher’s exact test. The proportions of adverse events were also described graphically. This analysis was performed considering: all AEs, grade 3 and 4 AEs and AEs leading to study treatment discontinuation or study withdrawal. The causal relationships with the treatment were also described in this section.
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End point type |
Primary
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End point timeframe |
At 90 days
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Notes [1] - Per Protocol [2] - Per Protocol |
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Statistical analysis title |
Fisher's exact test | ||||||||||||
Statistical analysis description |
In the primary analysis, the proportions of adverse events up to day 90 were described and compared between treatment arms using a Fisher’s exact test.
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Comparison groups |
Placebo Arm v Experimental Arm
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Number of subjects included in analysis |
49
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Analysis specification |
Post-hoc
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Analysis type |
equivalence | ||||||||||||
P-value |
> 0.9 | ||||||||||||
Method |
Fisher exact | ||||||||||||
Confidence interval |
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End point title |
Proportion of adverse events (AEs) through day 90, considering: Grade 3 and 4 AEs | ||||||||||||
End point description |
In the primary analysis, the proportions of adverse events up to day 90 were described and compared between treatment arms using a Fisher’s exact test.
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End point type |
Primary
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End point timeframe |
At 90 days
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Notes [3] - Per Protocol [4] - Per Protocol |
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Statistical analysis title |
Fisher's exact test | ||||||||||||
Comparison groups |
Experimental Arm v Placebo Arm
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Number of subjects included in analysis |
49
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Analysis specification |
Post-hoc
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Analysis type |
equivalence | ||||||||||||
P-value |
= 0.5 | ||||||||||||
Method |
Fisher exact | ||||||||||||
Confidence interval |
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End point title |
Proportion of adverse events (AEs) through day 90: AEs leading to study withdrawal | ||||||||||||
End point description |
In the primary analysis, the proportions of adverse events up to day 90 were described and compared between treatment arms using a Fisher’s exact test.
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End point type |
Primary
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End point timeframe |
At 90 days
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Notes [5] - Per Protocol [6] - Per Protocol |
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Statistical analysis title |
Fisher's exact test | ||||||||||||
Comparison groups |
Experimental Arm v Placebo Arm
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Number of subjects included in analysis |
49
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Analysis specification |
Post-hoc
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Analysis type |
equivalence [7] | ||||||||||||
P-value |
= 0.3 | ||||||||||||
Method |
Fisher exact | ||||||||||||
Confidence interval |
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Notes [7] - In the primary analysis, the proportions of adverse events up to day 90 were described and compared between treatment arms using a Fisher’s exact test. |
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End point title |
Proportion of participants with an improvement in PCFS score to grades 1-2 | ||||||||||||
End point description |
In the secondary analysis, the secondary endpoints were described through a table and graphically represented to evaluate its evolution over time. For the categorical endpoints sankey plots were used to describe the evolution of each category over time.
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End point type |
Secondary
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End point timeframe |
At 90 days
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Notes [8] - Per Protocol [9] - Per Protocol |
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No statistical analyses for this end point |
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End point title |
Evaluation fatigue severity scale (FSS) | ||||||||||||
End point description |
No changes were observed in the fatigue severity scale between the two groups during the study period.
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End point type |
Secondary
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End point timeframe |
At 90 days
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Notes [10] - Per Protocol [11] - Per protocol |
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No statistical analyses for this end point |
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End point title |
Evolution of the mean score of the Can Ruti PCC symptoms scale in the two groups over time | ||||||||||||
End point description |
Symptom Assessment (Can Ruti Scale): No significant changes were found in the progression of the Can Ruti Symptom Assessment Scale throughout the trial in both groups.
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End point type |
Secondary
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End point timeframe |
At 90 days
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No statistical analyses for this end point |
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End point title |
Evolution of the mean score of EuroQol-5D in the two groups over time - PP population | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
At 90 days
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Notes [12] - Per Protocol [13] - Per Protocol |
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No statistical analyses for this end point |
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End point title |
Evolution of the physical health component of MOS-HIV in the two groups over time (Really good)) | ||||||||||||
End point description |
% of participants indicated "really good" in the health component of MOS-HIV at 90 days.
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End point type |
Secondary
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End point timeframe |
At 90 days
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Notes [14] - Per Protocol [15] - Per Protocol |
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No statistical analyses for this end point |
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End point title |
Evolution of the mean score of Neu Screen in the two groups over time - PP population | ||||||||||||
End point description |
Evolution of the mean score of Neu Screen in the two groups over time - PP population (TMT-F+A+S)
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End point type |
Secondary
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End point timeframe |
At 90 days
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Notes [16] - PP population [17] - PP population |
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No statistical analyses for this end point |
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End point title |
Evolution of the mean score of the semantic fluency test in the two groups over time - PP population | ||||||||||||
End point description |
Evolution of the mean score of the semantic fluency test in the two groups over time - PP population
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End point type |
Secondary
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End point timeframe |
At 90 days
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Notes [18] - PP population [19] - PP population |
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No statistical analyses for this end point |
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End point title |
Evolution of the mean score of MEF-30 in the two groups over time - PP population | ||||||||||||
End point description |
Evolution of the mean score of MEF-30 in the two groups over time - PP population
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End point type |
Secondary
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End point timeframe |
At 90 days
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Notes [20] - Per Protocol [21] - Evolution of the mean score of MEF-30 in the two groups over time - PP population |
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No statistical analyses for this end point |
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End point title |
Evolution of the laboratory analysis profile of the two groups over time: FIBRINOGEN | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
At 90 days
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No statistical analyses for this end point |
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End point title |
Evolution of the laboratory analysis profile of the two groups over time: D-Dimer | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
At 90 days
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Notes [22] - Per Protocol [23] - Per Protocol |
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
At 90 days
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Adverse event reporting additional description |
A safety analysis was also conducted, considering adverse events on both a per-subject basis and a per-event basis.
Statistical analyses were performed with R software version 4.3.0 or higher and the most commonly used packages were gtsummary, ggplot2 and lme4.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
26.1
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Reporting groups
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Reporting group title |
Experimental Group
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Reporting group description |
6 sessions of PE (Plasma Exchange) with human serum albumin. Plasma exchange sessions will occur on days 1, 3, 8, 10, 15 and 17. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Control Group
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Reporting group description |
6 sessions with placebo (infusion of 200 to 250ml of sterile saline solution 0.9%) on days 1, 3, 8, 10, 15 and 17. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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22 Jun 2022 |
To obtain the maximum information from participants diagnosed with Post-COVID-19 Syndrome (SPC), it is decided to add more parameters to be analyzed during the study, so the following documents are modified:
- Protocol: New version 3.0, 06/22/2022
- Protocol Summary: New version 3.0, 06/22/2022
- HIP/CI: New version 4.0, 06/22/2022
- Annex IV: MOS-VIH (Annex IV (SF-36) is replaced by the MOS-VIH questionnaire.
- Annex III: The version of the symptomatology questionnaire is updated.
- Annex VI: The neurocognitive evaluation is added, based on the completion of 3 “Neuropsychological Assessment” questionnaires |
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19 Dec 2022 |
To obtain the maximum information from participants diagnosed with Post-COVID-19 Syndrome (PCS), it is decided to add an extra visit in case the participant presents re-infection by COVID-19, and it will be considered appropriate to carry out all the visits established by protocol, in case the participant has to prematurely discontinue the study treatment.
Due to these changes, the following documentation is generated:
- Protocol: New version 4.0, 12/19/2022
- Protocol Summary: New version 4.0, 12/19/2022
- HIP/CI: New version 5.0, 12/19/2022 |
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |