Cervicothoracic Sympathetic Block Evaluation for Post COVID Condition

NCT07468604 | Recruiting Phase 4

• 1 other identifier: 5627
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 2

Brief Summary

Post-COVID Condition (PCC) affects roughly 2.1 million Canadians, carrying an annual economic burden of CAD $7.8-50.6 billion. It presents across multiple organ systems with symptoms including fatigue, brain fog, palpitations, and orthostatic intolerance, at an annual cost of CAD $1,675-$7,340 per case. A key mechanism underlying many treatment-resistant PCC symptoms appears to be dysautonomia abnormal autonomic nervous system function driven by immune-mediated sympathetic overactivity. Persistent inflammation (cytokine storms, T/B-cell dysfunction, microclots) sustains sympathetic hyperactivity, which in turn perpetuates systemic inflammation and "sickness behaviors" resembling PCC symptoms. Current treatments including beta blockers, ivabradine, fludrocortisone, and rehabilitation are limited by variable responses, side effects, and the complication of post-exertional symptom exacerbation. Emerging therapies (SSRIs, low-dose naltrexone, antihistamines, HBOT) show promise but lack robust trial evidence. Cervicothoracic sympathetic chain block (CSB) a local anesthetic block of the cervical and upper thoracic sympathetic ganglia is a promising intervention that reduces sympathetic outflow, improves cerebral blood supply, and lowers pro-inflammatory cytokines. Small observational studies (16 studies, 224 patients) show benefit for PCC symptoms, but all lack placebo controls and have significant methodological heterogeneity. The proposed study aims to fill this gap with a double-blind, placebo-controlled RCT to rigorously evaluate CSB's efficacy, magnitude of benefit, and durability in PCC patients.

Conditions

Autonomic Dysfunction

Outcome Measures

Primary Outcomes (1)

• Change from baseline in the Modified COVID-19 Yorkshire Rehabilitation Scale (C19-YRSm) Symptom Severity subscale score

  Description: The C19-YRSm Symptom Severity subscale is scored from 0 to 30, with higher scores indicating greater symptom burden. The outcome is the change from baseline in this score.

  Three months after the final injection.

Secondary Outcomes (13)

• C19-YRSm Symptom Severity subscale score

  One month and three months after the final injection.

• Autonomic symptom burden (COMPASS-31)

  collected at screening, one month and three months after the final injection.

• Heart rate variability

  collected at screening, one month and three months after the final injection.

• Heart rate and blood pressure responses to autonomic challenge

  collected at screening, one month and three months after the final injection.

• One-minute sit-to-stand test.

  collected at screening, one month and three months after the final injection.

Other Outcomes (5)

• Incidence of adverse events and serious adverse events.

  from the first injection to the three-month assessment

• Proportion of participants with a reduction of ≥4 points on the C19-YRSm Symptom Severity subscale

  one month after the final injection

• Difference in treatment effect between participants with and without postural orthostatic tachycardia syndrome (POTS), not powered for interaction; hypothesis-generating.

  one month after the final injection

Study Arms (2)

Active group

EXPERIMENTAL

The active group will have cervical sympathetic block (CSB) on both the left and right sides using up to 5 mL of 0.25% bupivacaine with epinephrine (1:200,000).

Drug: 5 mL of 0.25% bupivacaine with epinephrine (1:200,000)

Placebo (Saline) Control

PLACEBO COMPARATOR

Participants will receive cervicothoracic sympathetic chain block (CSB) on both the left and right sides using up to 5 mL of normal saline (0.9% NaCl), by an identical ultrasound-guided approach to the active arm. After the injection, all participants will be monitored for a minimum of 30 minutes for expected effects of the block and for side effects or complications.

Other: Placebo (Saline) Control

Interventions

5 mL of 0.25% bupivacaine with epinephrine (1:200,000) DRUG

The active group will have cervical sympathetic block (CSB) on both the left and right sides using up to 5 mL of 0.25% bupivacaine with epinephrine (1:200,000). After the injection, all patients will be monitored for a minimum of 30 minutes to check for expected effects of the block and to watch for any side effects or complications.

Also known as: Active group

Active group

Placebo (Saline) Control OTHER

Participants will receive cervicothoracic sympathetic chain block (CSB) on both the left and right sides using up to 5 mL of normal saline (0.9% NaCl), by an identical ultrasound-guided approach to the active arm. After the injection, all participants will be monitored for a minimum of 30 minutes for expected effects of the block and for side effects or complications.

Also known as: 5 ml of normal saline (0.9% NaCl)

Placebo (Saline) Control

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Self-identified gender: Male/Female/Trans/Non-binary/Prefer not to disclose
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 years or older
• PCC following COVID-19 infection with symptoms lasting for at least three months
• Ability to read, write, and understand English
• Quantified autonomic symptoms from at least one domain as reported by the patient on the screener Composite Autonomic Symptom Score (COMPASS-31), i.e. a COMPASS-31 score greater than 0. COMPASS-31 assesses 6 domains of autonomic symptoms: Orthostatic Intolerance, Vasomotor, Secretomotor, Gastrointestinal, Bladder, and Pupillomotor.
• Patients should be stable on any PCC-related medications for at least four weeks.

You may not qualify if:

• History of co-existing conditions that are a contraindication for CSB:
• Unilateral vocal cord paralysis; Severe chronic obstructive pulmonary disease (FEV1 between 30-50% of predicted value)
• Recent myocardial infarction (within the last one year), Cardiac conduction block of any degree
• Glaucoma
• Infection or mass at injection site, bleeding disorders
• Comorbid conditions that could confound study results, such as:
• Active autoimmune disorders
• Pre-existing autonomic dysfunction (e.g. POTS, IST, and CRPS) prior to COVID-19
• Untreated psychiatric conditions (e.g. severe anxiety or PTSD requiring medication adjustments during the study period)
• Recent history of major surgery or cerebrovascular events within the last three months
• Allergy to local anesthetic; Inability to extend the neck for any reason (e.g. severe arthritis)
• History of prior stellate ganglion block

Sponsors & Collaborators

• University Health Network, Toronto: lead

Study Sites (2)

Women's College Hospital

Toronto, Ontario, M5S 1B3, Canada

NOT YET RECRUITING

Toronto Western Hospital

Toronto, Ontario, M5T 2S8, Canada

RECRUITING

MeSH Terms

Conditions

Primary Dysautonomias

Interventions

Bupivacaine; Epinephrine; Sodium Chloride; Saline Solution

Condition Hierarchy (Ancestors)

Autonomic Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Ethanolamines; Amino Alcohols; Alcohols; Biogenic Monoamines; Biogenic Amines; Catecholamines; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Anuj Bhatia, MD, PhD

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Emad Al Azazi, MD, PhD

CONTACT

4166035800; emad.al-azazi@uhn.ca

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This will be a randomized control trial with allocation concealment from and blinding of both participants and outcome assessors.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Two-arm, double-blind randomized controlled trial (RCT) is to evaluate whether a series of two Cervicothoracic Sympathetic Block (CSB) over a 6-week epoch with local anesthetics are superior to a placebo injection of saline in alleviating cardiac dysautonomia-related symptoms in patients with PCC at one month after the interventions. The secondary goals include assessment of dysautonomia-related symptoms in patients with Post COVID Condition (PCC) at three months after the interventions, changes in pro-inflammatory cytokines, the effects of stellate ganglion blocks on beat-to-beat variations in heart rate and blood pressure associated with postural changes in patients with PCC, and any adverse effects at one and three months after the interventions.

Study Record Dates

• First Submitted: February 26, 2026
• First Posted: March 12, 2026
• Study Start: May 19, 2026
• Primary Completion (Estimated): May 20, 2027
• Study Completion (Estimated): September 1, 2027
• Last Updated: September 29, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Beginning nine months after publication of the primary results and ending five years thereafter.
• Access Criteria: Requests should be directed to the corresponding author. Requesters must submit a methodologically sound proposal and sign a data sharing agreement.

Locations

CA (2)