Cervicothoracic Sympathetic Block Evaluation for Post COVID Condition
ConditionAutonomic Dysfunction
Trial statusRecruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexAll
Age18+
SponsorUniversity Health Network, Toronto
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
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
Trial design
Design model
Parallel
Treatments tested in this trial
5 mL of 0.25% bupivacaine with epinephrine (1:200,000)
DrugThe 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.
Placebo (Saline) Control
Other interventionParticipants 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.
Treatment groups
78 Participants
are divided into 2 treatment groupsGroup A: Active groupExperimental treatment 1 intervention
Group B: Placebo (Saline) ControlPlacebo comparator 1 intervention
Trial outcomes
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.
Time frame
One month after the final injection.Secondary outcomes
1
C19-YRSm Symptom Severity subscale score
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.
Time frame
Three months after the final injection.2
Autonomic symptom burden (COMPASS-31)
Weighted total score and the six domain scores (orthostatic intolerance, vasomotor, secretomotor, gastrointestinal, bladder, pupillomotor).
Time frame
collected at screening, one month and three months after the final injection.3
Heart rate variability
Heart rate variability over a five-minute recording.
Time frame
collected at screening, one month and three months after the final injection.4
Heart rate and blood pressure responses to autonomic challenge
Valsalva manoeuvre, deep breathing, hyperventilation, and postural change (lying to sitting; sitting to standing).
Time frame
collected at screening, one month and three months after the final injection.Other outcomes
1
Incidence of adverse events and serious adverse events.
Events will be reported by arm, with needle-related events tabulated separately from drug-related and sympatholysis-related events.
Time frame
from the first injection to the three-month assessment2
Proportion of participants with a reduction of ≥4 points on the C19-YRSm Symptom Severity subscale
The threshold is taken from the reported MCID and is not a validated responder definition
Time frame
one month after the final injection3
Difference in treatment effect between participants with and without postural orthostatic tachycardia syndrome (POTS), not powered for interaction; hypothesis-generating.
Difference in treatment effect between participants with and without postural orthostatic tachycardia syndrome (POTS) not powered for interaction; hypothesis-generating.
Time frame
one month after the final injection4
Difference in treatment effect by baseline autonomic symptom burden
COMPASS-31 weighted total above versus below the cohort median; not powered for interaction.
Time frame
one month after the final injectionSponsors and contacts
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Source ClinicalTrials.gov