Effect of subcutaneous lidocaine-hydroxypropyl-β-cyclodextrin (HP-β-CD) on quality of life in patients with post-COVID condition: a 36-week observational interrupted time series study

Cees-Jan Oostwouder; Karin Vos; Ivo J Lutke Schipholt; Mathijs R Merkus; Thomas Telders; David F A van Deursen; Max B de Smit; Marina D van Eijk; Hetty J Bontkes; Femke H Bouwman; Rob C I Wüst; Lara de Jong; Marinus van Hulst; Jos W R Twisk; Coenraad K van Kalken; Gwendolyne G M Scholten-Peeters

doi:10.1016/j.eclinm.2025.103681

Effect of subcutaneous lidocaine-hydroxypropyl-β-cyclodextrin (HP-β-CD) on quality of life in patients with post-COVID condition: a 36-week observational interrupted time series study

Cees-Jan Oostwouder
, Karin Vos
, Ivo J Lutke Schipholt
, Mathijs R Merkus
, Thomas Telders
, David F A van Deursen
, Max B de Smit
, Marina D van Eijk
, Hetty J Bontkes
, Femke H Bouwman
, Rob C I Wüst
, Lara de Jong
, Marinus van Hulst
, Jos W R Twisk
, Coenraad K van Kalken
, Gwendolyne G M Scholten-Peeters

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

BACKGROUND: Post-COVID involves persistent, multisystem symptoms which are associated with inflammation, immune dysregulation, and autonomic dysfunction. The effects of currently applied treatments for post-COVID are limited. This study assessed the effectiveness of subcutaneous lidocaine-hydroxypropyl-β-cyclodextrin (HP-β-CD) for the treatment of post-COVID.

METHODS: This interrupted time series study was conducted at a Dutch outpatient clinic between August 2024 and April 2025. Adults with physician-diagnosed post-COVID (n = 103) underwent a 4-week pre-treatment observation followed by 24-36 weeks of home-based subcutaneous lidocaine 5% with HP-β-CD, administered using a 3-phase protocol: 500 mg every other day (weeks 1-7), 500 mg daily (weeks 7-14), and up to 1000 mg/day (after week 14, in non-responders). The primary outcome was health-related quality of life (Short Form-12 (SF-12), physical and mental component summary scores). Secondary outcomes included symptom burden (daily app-based questionnaire) and adverse events.

FINDINGS: Among 103 participants (mean [SD] age 48·1 [13·0] years; 67% women; median [IQR] symptom duration 31·5 [24·3-43·3] months), 76% completed 24 weeks and 71% completed 36 weeks of treatment. At week 24, the physical and mental component scores increased by 2·20 and 5·16 points, respectively; at week 36, by 4·13 and 7·00 points (all p < 0·0001). Twenty-seven of 30 symptoms improved significantly at week 24 of treatment compared to pre-treatment. Mild adverse events occurred in 89% of participants, mostly injection-site reactions; no serious adverse events were reported.

INTERPRETATION: Subcutaneous lidocaine-HP-β-CD was associated with significantly improved quality of life and symptom burden in patients with post-COVID. This home-administered intervention offers a scalable and potentially disease-modifying approach for a disabling condition with no approved treatment to date.

FUNDING: Excellent Care Clinics funded the treatment provided in this study.

Original language	English
Article number	103681
Pages (from-to)	103681
Journal	EClinicalMedicine
Volume	90
DOIs	https://doi.org/10.1016/j.eclinm.2025.103681
Publication status	Published - Dec 2025

Bibliographical note

Funding

We thank the Department of Clinical Pharmacy and Toxicology at Martini Hospital, The Netherlands, for their support in the production of the magistral formulation used in this study. We also thank Dr. Ferdi Sombogaard for performing the lidocaine plasma level measurements and Prof. Seb. Marcuccio from Advanced Molecular Technologies, Melbourne Australia, for providing guidance in the design of the formulation. Excellent Care Clinics funded the treatment provided in this study.

Funders
Department of Clinical Pharmacy

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https://pmc.ncbi.nlm.nih.gov/articles/PMC12719765/

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Oostwouder, C.-J., Vos, K., Lutke Schipholt, I. J., Merkus, M. R., Telders, T., van Deursen, D. F. A., de Smit, M. B., van Eijk, M. D., Bontkes, H. J., Bouwman, F. H., Wüst, R. C. I., de Jong, L., van Hulst, M., Twisk, J. W. R., van Kalken, C. K., & Scholten-Peeters, G. G. M. (2025). Effect of subcutaneous lidocaine-hydroxypropyl-β-cyclodextrin (HP-β-CD) on quality of life in patients with post-COVID condition: a 36-week observational interrupted time series study. EClinicalMedicine, 90, 103681. Article 103681. https://doi.org/10.1016/j.eclinm.2025.103681

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title = "Effect of subcutaneous lidocaine-hydroxypropyl-β-cyclodextrin (HP-β-CD) on quality of life in patients with post-COVID condition: a 36-week observational interrupted time series study",

abstract = "BACKGROUND: Post-COVID involves persistent, multisystem symptoms which are associated with inflammation, immune dysregulation, and autonomic dysfunction. The effects of currently applied treatments for post-COVID are limited. This study assessed the effectiveness of subcutaneous lidocaine-hydroxypropyl-β-cyclodextrin (HP-β-CD) for the treatment of post-COVID.METHODS: This interrupted time series study was conducted at a Dutch outpatient clinic between August 2024 and April 2025. Adults with physician-diagnosed post-COVID (n = 103) underwent a 4-week pre-treatment observation followed by 24-36 weeks of home-based subcutaneous lidocaine 5\% with HP-β-CD, administered using a 3-phase protocol: 500 mg every other day (weeks 1-7), 500 mg daily (weeks 7-14), and up to 1000 mg/day (after week 14, in non-responders). The primary outcome was health-related quality of life (Short Form-12 (SF-12), physical and mental component summary scores). Secondary outcomes included symptom burden (daily app-based questionnaire) and adverse events.FINDINGS: Among 103 participants (mean [SD] age 48·1 [13·0] years; 67\% women; median [IQR] symptom duration 31·5 [24·3-43·3] months), 76\% completed 24 weeks and 71\% completed 36 weeks of treatment. At week 24, the physical and mental component scores increased by 2·20 and 5·16 points, respectively; at week 36, by 4·13 and 7·00 points (all p < 0·0001). Twenty-seven of 30 symptoms improved significantly at week 24 of treatment compared to pre-treatment. Mild adverse events occurred in 89\% of participants, mostly injection-site reactions; no serious adverse events were reported.INTERPRETATION: Subcutaneous lidocaine-HP-β-CD was associated with significantly improved quality of life and symptom burden in patients with post-COVID. This home-administered intervention offers a scalable and potentially disease-modifying approach for a disabling condition with no approved treatment to date.FUNDING: Excellent Care Clinics funded the treatment provided in this study.",

author = "Cees-Jan Oostwouder and Karin Vos and \{Lutke Schipholt\}, \{Ivo J\} and Merkus, \{Mathijs R\} and Thomas Telders and \{van Deursen\}, \{David F A\} and \{de Smit\}, \{Max B\} and \{van Eijk\}, \{Marina D\} and Bontkes, \{Hetty J\} and Bouwman, \{Femke H\} and W{\"u}st, \{Rob C I\} and \{de Jong\}, Lara and \{van Hulst\}, Marinus and Twisk, \{Jos W R\} and \{van Kalken\}, \{Coenraad K\} and Scholten-Peeters, \{Gwendolyne G M\}",

note = "{\textcopyright} 2025 The Author(s).",

year = "2025",

month = dec,

doi = "10.1016/j.eclinm.2025.103681",

language = "English",

volume = "90",

pages = "103681",

journal = "EClinicalMedicine",

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Oostwouder, C-J , Vos, K , Lutke Schipholt, IJ, Merkus, MR, Telders, T, van Deursen, DFA, de Smit, MB, van Eijk, MD, Bontkes, HJ, Bouwman, FH, Wüst, RCI, de Jong, L, van Hulst, M, Twisk, JWR, van Kalken, CK & Scholten-Peeters, GGM 2025, 'Effect of subcutaneous lidocaine-hydroxypropyl-β-cyclodextrin (HP-β-CD) on quality of life in patients with post-COVID condition: a 36-week observational interrupted time series study', EClinicalMedicine, vol. 90, 103681, pp. 103681. https://doi.org/10.1016/j.eclinm.2025.103681

Effect of subcutaneous lidocaine-hydroxypropyl-β-cyclodextrin (HP-β-CD) on quality of life in patients with post-COVID condition: a 36-week observational interrupted time series study. / Oostwouder, Cees-Jan ; Vos, Karin ; Lutke Schipholt, Ivo J et al.
In: EClinicalMedicine, Vol. 90, 103681, 12.2025, p. 103681.

Research output: Contribution to Journal › Article › Academic › peer-review

TY - JOUR

T1 - Effect of subcutaneous lidocaine-hydroxypropyl-β-cyclodextrin (HP-β-CD) on quality of life in patients with post-COVID condition

T2 - a 36-week observational interrupted time series study

AU - Oostwouder, Cees-Jan

AU - Vos, Karin

AU - Lutke Schipholt, Ivo J

AU - Merkus, Mathijs R

AU - Telders, Thomas

AU - van Deursen, David F A

AU - de Smit, Max B

AU - van Eijk, Marina D

AU - Bontkes, Hetty J

AU - Bouwman, Femke H

AU - Wüst, Rob C I

AU - de Jong, Lara

AU - van Hulst, Marinus

AU - Twisk, Jos W R

AU - van Kalken, Coenraad K

AU - Scholten-Peeters, Gwendolyne G M

PY - 2025/12

Y1 - 2025/12

N2 - BACKGROUND: Post-COVID involves persistent, multisystem symptoms which are associated with inflammation, immune dysregulation, and autonomic dysfunction. The effects of currently applied treatments for post-COVID are limited. This study assessed the effectiveness of subcutaneous lidocaine-hydroxypropyl-β-cyclodextrin (HP-β-CD) for the treatment of post-COVID.METHODS: This interrupted time series study was conducted at a Dutch outpatient clinic between August 2024 and April 2025. Adults with physician-diagnosed post-COVID (n = 103) underwent a 4-week pre-treatment observation followed by 24-36 weeks of home-based subcutaneous lidocaine 5% with HP-β-CD, administered using a 3-phase protocol: 500 mg every other day (weeks 1-7), 500 mg daily (weeks 7-14), and up to 1000 mg/day (after week 14, in non-responders). The primary outcome was health-related quality of life (Short Form-12 (SF-12), physical and mental component summary scores). Secondary outcomes included symptom burden (daily app-based questionnaire) and adverse events.FINDINGS: Among 103 participants (mean [SD] age 48·1 [13·0] years; 67% women; median [IQR] symptom duration 31·5 [24·3-43·3] months), 76% completed 24 weeks and 71% completed 36 weeks of treatment. At week 24, the physical and mental component scores increased by 2·20 and 5·16 points, respectively; at week 36, by 4·13 and 7·00 points (all p < 0·0001). Twenty-seven of 30 symptoms improved significantly at week 24 of treatment compared to pre-treatment. Mild adverse events occurred in 89% of participants, mostly injection-site reactions; no serious adverse events were reported.INTERPRETATION: Subcutaneous lidocaine-HP-β-CD was associated with significantly improved quality of life and symptom burden in patients with post-COVID. This home-administered intervention offers a scalable and potentially disease-modifying approach for a disabling condition with no approved treatment to date.FUNDING: Excellent Care Clinics funded the treatment provided in this study.

AB - BACKGROUND: Post-COVID involves persistent, multisystem symptoms which are associated with inflammation, immune dysregulation, and autonomic dysfunction. The effects of currently applied treatments for post-COVID are limited. This study assessed the effectiveness of subcutaneous lidocaine-hydroxypropyl-β-cyclodextrin (HP-β-CD) for the treatment of post-COVID.METHODS: This interrupted time series study was conducted at a Dutch outpatient clinic between August 2024 and April 2025. Adults with physician-diagnosed post-COVID (n = 103) underwent a 4-week pre-treatment observation followed by 24-36 weeks of home-based subcutaneous lidocaine 5% with HP-β-CD, administered using a 3-phase protocol: 500 mg every other day (weeks 1-7), 500 mg daily (weeks 7-14), and up to 1000 mg/day (after week 14, in non-responders). The primary outcome was health-related quality of life (Short Form-12 (SF-12), physical and mental component summary scores). Secondary outcomes included symptom burden (daily app-based questionnaire) and adverse events.FINDINGS: Among 103 participants (mean [SD] age 48·1 [13·0] years; 67% women; median [IQR] symptom duration 31·5 [24·3-43·3] months), 76% completed 24 weeks and 71% completed 36 weeks of treatment. At week 24, the physical and mental component scores increased by 2·20 and 5·16 points, respectively; at week 36, by 4·13 and 7·00 points (all p < 0·0001). Twenty-seven of 30 symptoms improved significantly at week 24 of treatment compared to pre-treatment. Mild adverse events occurred in 89% of participants, mostly injection-site reactions; no serious adverse events were reported.INTERPRETATION: Subcutaneous lidocaine-HP-β-CD was associated with significantly improved quality of life and symptom burden in patients with post-COVID. This home-administered intervention offers a scalable and potentially disease-modifying approach for a disabling condition with no approved treatment to date.FUNDING: Excellent Care Clinics funded the treatment provided in this study.

U2 - 10.1016/j.eclinm.2025.103681

DO - 10.1016/j.eclinm.2025.103681

M3 - Article

C2 - 41438970

SN - 2589-5370

VL - 90

SP - 103681

JO - EClinicalMedicine

JF - EClinicalMedicine

M1 - 103681

ER -

Effect of subcutaneous lidocaine-hydroxypropyl-β-cyclodextrin (HP-β-CD) on quality of life in patients with post-COVID condition: a 36-week observational interrupted time series study

Abstract

Bibliographical note

Funding

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Cite this