Clinical trial NCT04445337
Conditions: COVID 19 ARDS
Keywords: stellate ganglion perineural block
Sponsor: University of Nebraska
Start date: 2020-11-15; Completion date: 2021-11-01
Enrollment: 1 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This study will establish the safety and efficacy of using stellate ganglion blocks in patients with acute respiratory distress syndrome (ARDS) due to COVID-19 disease.

Detailed description:
The stellate ganglion block (SGB) will be performed in the ICU. Nurse will provide patient monitoring and assistance during the procedure. Standard monitors and advanced cardiovascular life support (ACLS) resuscitative equipment will be immediately available. A norepinephrine solution will be at bedside to treat potential hypotension associated with SGB. The SGB perineural catheter will be placed using standard sterile technique. Initial perineural bolus injection - clonidine 100 mcg, Decadron sodium phosphate (PF) 5mg, and 0.25% bupivacaine 5 ml is delivered. An ONQ brand perineural infusion 0.2% bupivacaine will be initiated at 2ml/hr for 5 days. Acute pain service will discontinue infusion and remove the catheter after 5 days.

Arms: arm 1: Initial perineural bolus injection - clonidine 100 mcg, Decadron PF 5mg, and 0.25% bupivacaine 5 ml will be used for SGB block. arm 2: There will be no sham procedure for the control group. The control group will have nitric oxide levels performed once a day by a member of the research team. Lab draws will be drawn at the same frequency as the treatment group.
Interventions: intervention 1: Stellate Ganglion Block
Intervention descriptions: intervention 1: An injection of local anesthetic into the front of the neck. SGB involves placing a small tube into the front of your neck, toward nerves at the back of your neck. This is done with the help of an x-ray machine or ultrasound device. The tube is left in place so you can get medication thru it for five days. Then the tube is taken out.

The medication used for the block are clonidine 100 mcg, Decadron PF 5mg and 0.25% bupivacaine 5 mL. This medication will be administered once during the block. These medications are approved by the Food and Drug Administration (FDA).

Protocol documents:
Prot_SAP_000.pdf: 
SGB IN COVID-19 VERSION 3.0 NOVEMBER 23, 2020 
1 
 
Stellate Ganglion Blockade in COVID-19 Positive Patients 
NCT04445337 
23 Nov 2020 
 


SGB IN COVID-19 VERSION 3.0 NOVEMBER 23, 2020 
2 
 
 
Stellate Ganglion Blockade in COVID-19 
Positive Patients 
 
 


SGB IN COVID-19 VERSION 3.0 NOVEMBER 23, 2020 
3 
 
 
Title Page …………………………………………………………………… 
 
Summary……………………………………………………………………. 
 
Section 1.0 
Objectives ……………………………………………………  
 
Section 2.0 
Introduction, which includes background data and future aims  
 
Section 3.0 
Eligibility criteria ……………………………………………... 
 
Section 4.0 
Randomization/registration procedures ……………………... 
Section 5.0 
Treatment plan or research design …………………………..... 
 
Section 6.0 
Measurement of effect …………………………..……………. 
 
Section 7.0 
Study parameters ……………………………...……………… 
 
Section 8.0 
Drug dosage………………………. ………………………….. 
 
Section 9.0  
Adverse event reporting guidelines ……………........................ 
 
Section 10.0 Biostatistic considerations including stopping criteria …….. 
 
Section 11.0  Records to be kept ………………………………………...…… 
 
Section 12.0 Patient consent form statement ……………………………….. 
 
Section 13.0    Study and Safety monitoring DSMB…………………………..  
Section 14.0 References ……………………………………………………. 
Appendix A.  ………………………………………………………………….. 
Appendix B.   ………………………………………………………………….
 
 
 
 
3 
4 
4 
4-8 
8 
9 
9-11 
12-13 
13-15 
14-15 
14-15 
15 
16 
17 
18-19 
20 
21-25
 


SGB IN COVID-19 VERSION 3.0 NOVEMBER 23, 2020 
4 
 
STELLATE GANGLION BLOCKAGE IN COVID-19 POSITIVE PATIENTS 
IRB#523-20-FB 
Principal Investigator: 
 
Michael Lankhorst, M.D.  
Assistant Professor 
Director of Pain Clinics 
Pain Medicine/Anesthesiology 
University of Nebraska Medical Center 
Supported by: 
 
Department of Anesthesiology 
University of Nebraska Medical Center 
 
UNMC Nebraska Neuroscience Alliance COVID-19 Rapid Response Grants 
 
NCT Number: 
04445337 
 
 
 
 
 
 
 
 
 


SGB IN COVID-19 VERSION 3.0 NOVEMBER 23, 2020 
5 
 
Brief Summary:  
The proposed research plan will reflect the proof of concept of our modified stellate ganglion 
block in the human subject, following several key cardiac and pulmonary parameters leading to 
clinical benefit as well as the safety aspects of stellate ganglion blockade (SGB). Enrolling 
subjects will be enrolled from patients cared for in the COVID ICU/progressive care at Nebraska 
Medicine.   
Patient eligibility will be determined based on the following criteria;  Any patient between the ages 
of 40-75 with laboratory established COVID-19 infection (via rRT-PCR) requiring critical care in 
an intensive care unit, signs or symptoms consistent with ARDS, at least 2 of the following 
(respiratory rate ≥30 breaths per min, oxygen saturation at rest ≤ 93%, PaO2/FIO2 ≤ 200 mm Hg, 
bilateral infiltrates on chest radiograph or CT not due to cardiac failure, requiring non-invasive or 
invasive mechanical ventilation.)  Block randomization will be used to determine equal allocation 
to control (labs, nitric oxide levels +SOC) and intervention group (labs, nitric oxide levels, SGB 
procedure, perineural catheter 5 days). Once enrollment criteria are met, baseline assessments will 
be completed by the Acute Pain Service (APS).  They will place SGB and manage intervention 
group for 5 days. Data collection will be collected through Day 5 of hospital stay, discharge 
information will be documented, and survival at 90 days via telephone to complete SF 36 
questionnaire.  
 
Section 1.0 Objectives:  
 
To assess the safety, tolerance, oxygenation, lung and cardiac function, proinflammatory 
immune response and nitric oxide changes associated with the use of our modified SGB protocol 
in patients with ARDS due to COVID-19 disease. 
 
Secondary (to be confirmed at later trial phase): To determine the association of use of our 
modified SGB protocol in patients with ARDS due to COVID-19 disease on: incidence of 
cardiac arrhythmias associated with ARDS, need and duration of use of mechanical ventilation 
and extracorporeal membrane oxygenation (ECMO). 
 
Section 2.0 Introduction:  
The novel coronavirus, now officially designated as severe acute respiratory syndrome 
coronavirus-2 or SARS-CoV-2 was first identified in Wuhan, Hubei Province, China in 
December of 2019. Since its identification, Coronavirus disease 2019 (COVID-19) has evolved 
into an international public health emergency. As is common for the coronavirus family, (SARS-
CoV-1 and MERS), COVID-19 is associated with acute respiratory infection.  The mortality of 
COVID-19 infection is mostly due to complications related to pneumonia and ARDS 1. 
Strategies to mitigate ARDS and consequent multi-organ failure is in high demand. Currently, 
there are no FDA-approved treatments outside of supportive care for patients suffering from 
ARDS due to COVID-19. Unique to COVID-19 associated respiratory failure and ARDS is the 
early overproduction of proinflammatory cytokines. This exaggerated immune response or 
“cytokine storm,” is felt to lead to increased vascular hyperpermeability, multiorgan failure, and 
death.  Many ARDS/lung injury patients manifest refractory hypoxia, cardiac arrhythmias and 
acute myocardial damage10-13. Cardiovascular complications such as circulatory failure are 


SGB IN COVID-19 VERSION 3.0 NOVEMBER 23, 2020 
6 
 
frequently associated with COVID-19 ARDS and are associated with a poor outcome14. Case 
series have noted cardiac arrhythmias, cardiomyopathy, and cardiac arrest as terminal events in 
Covid-1915-17. Stellate ganglia block (SGB) is a common clinical intervention to treat both 
sympathetic nervous system overstimulation and refractory cardiac arrhythmia. Traditional 
chemo-neuromodulation paradigms employ a single SGB strategy deriving short-term (lasting a 
few hours to one day) control of sympathetically mediated symptoms, e.g., cardiac arrhythmias 
are controlled by temporarily blocking stellate neuronal activity with local anesthetics18-20. Once 
the anesthetic effect is withdrawn, cardiac arrhythmias recur. We propose a modified SGB 
strategy utilizing a continuous infusion of medications instead of a bolus injection.  We expect to 
achieve a lasting chemo-neuromodulating effect in COVID-19 ARDS patients reducing overall 
inflammation, improving pulmonary function, and reducing cardiac complications.   
Preliminary Data: A notable innovation of our modified SGB approach is the addition of 
clonidine and dexamethasone to a local anesthetic (LA). The scientific rationale supporting 
this modification is derived from both the literature as well as work done here at UNMC by 
Dr. Hanjun Wang (Figure 1).  
 
 
 


SGB IN COVID-19 VERSION 3.0 NOVEMBER 23, 2020 
7 
 
Recent animal studies from Dr. Wang’s lab suggest macrophage activation in stellate ganglia 
plays a critical role in mediating acute lung injury-caused cardiac arrhythmia (Figure 2).  
 
 
Additionally, systemic administration of an anti-inflammatory medicine, minocycline, can 
largely block macrophage activation and arrhythmias in a bleomycin-induced lung injury rat 
model (Figure 3).  


SGB IN COVID-19 VERSION 3.0 NOVEMBER 23, 2020 
8 
 
 
Dr. Wang’s findings support the novel concept that local delivery of anti-inflammatory/anti-
macrophage medicine to/around the stellate ganglia may be a promising new therapy for 
treatment of inflammation-augmented comorbidities (especially cardiac) in acute lung 
injury/ARDS patients. To test this hypothesis in humans, we propose addition of two 
medications to the LA-SGB.  Low dose dexamethasone will be added to ameliorate stellate 
ganglia inflammation directly. Additionally, based on Dr. Wang’s work, we will also add 
clonidine.  This additive is supported in that 1) clonidine selectively stimulates α2 adrenergic 
receptor and promotes the norepinephrine reuptake by cardiac sympathetic nerve endings 20-
22 ) clonidine has local anti-inflammatory effects via promoting apoptosis of leukocytes and 
switching pro-inflammatory macrophage to anti-inflammatory macrophage23. In addition to 
testing, the beneficial cardiac effects of our modified SGB approach, we also aim to examine 
if SGB could also improve lung damage/inflammation as well as respiratory function in 
COVID 19 patients. This work is also previously performed in animal models.  In septic rats, 


SGB IN COVID-19 VERSION 3.0 NOVEMBER 23, 2020 
9 
 
SGB was able to attenuate sepsis related lung injury and decrease serum levels of TNF-alpha 
and IL-63.  In a direct lung injury model using rabbits, SGB showed decreased levels of TNF-
alpha, IL-6 and IL-10 as well as decreased postmortem acute lung injury4. Human studies in 
trauma patients revealed immunological findings of decreased pro inflammatory cytokine 
production, and no negative effect on cardiovascular or pulmonary parameters.2 Finally, in 
one small human study of patients undergoing one-lung ventilation, SGB was shown 
associated with increased plasma levels of nitric oxide and improved oxygenation5.   In 
animal models, SGB was shown to improve pulmonary hypertension via NO production; 
oxygenation was improved as well.6-7 Several studies show nitric oxide can directly inhibit 
RNA synthesis, viral protein accumulation and virus released from infected cells.  This was 
found in a variety of viruses, but specifically SARS.  Not only was replication of the virus 
reduced, by NO was found to block SARS binding to the receptor host.8-9 We expect that the 
modified SGB strategy will achieve prolonged anti-arrhythmia and anti-inflammatory effects 
in COVID patients.  
 
Study Rationale: 
Available research indicates that an exaggerated immune response plays a key role in the 
cardiopulmonary pathophysiology of COVID-19. Preliminary data from previous studies at 
UNMC suggest that acute lung injury initiates robust and sustained macrophage activation in 
thoracic dorsal root ganglia and in stellate ganglia, resulting in increased cardiac and 
pulmonary afferent and efferent neuronal sensitivity. In the current proposal, we plan to 
validate a novel therapeutic strategy to treat coronavirus-induced cardiopulmonary symptoms 
and complications by local delivery of bupivacaine, dexamethasone, and clonidine to the 
stellate ganglia.  Single injection and continuous infusion SGB have been safely 
utilized clinically and in many human studies.  
 
Section 3.0 Eligibility Criteria:  
 
Inclusion:  
• Subject admitted to COVID ICU/progressive care, age 40-75 years old 
 
Subjects must have + covid test with signs of impending respiratory compromise as identified 
by having at least 2 of the following:  
• Respiratory rate ≥30 breaths per min 
• Oxygen saturation at rest ≤ 93% 
• PaO2/FIO2 ≤ 200 mm Hg 
• bilateral infiltrates on chest radiograph or CT not due to cardiac failure 
• Requiring non-invasive or invasive mechanical ventilation.  
Any patient with a + covid test and any cardiac tachydysrhythmia (excluding sinus tachycardia) 
will be included regardless of respiratory status. (Note: The broader inclusion of patients who 
have cardiac tachydysrhythmia is based on our prior experience and other reported beneficial 
antiarrhythmic effects of SGB in this patient group.) 


SGB IN COVID-19 VERSION 3.0 NOVEMBER 23, 2020 10 
 
 
 
Exclusion:  
• Hemodynamic instability (>2 vasopressors)  
• Heart rate < 60 beats per minute 
• Systolic Blood pressure of less than 80 mmHg 
• pre-hospital diagnosis of heart failure or fluid overload  
• anatomical inability to perform block  
• prior sympathectomy  
• Patient currently enrolled in another clinical trial for COVID-19 or respiratory 
distress/ARDs  
• Uncorrectable coagulopathy  
• ECMO already engaged  
• On Nitric Oxide  
• Pre-existing multi-organ failure (>2 organ systems)  
• Allergic to dexamethasone, clonidine, or bupivacaine.  
• If female, currently pregnant or breast-feeding.  
• Investigators determine the subject would be too unstable to participate in the study 
intervention.  
 
If a woman of childbearing age is enrolled as a subject and there has not been a pregnancy test 
during their current inpatient stay, a urine or blood pregnancy test will be performed. Pregnancy 
will not be allowed for this study as the drug is absorbed systemically and there are known risks 
to the fetus. 
 
 
Section 4.0 Registration Procedure:  
A prospective block randomized phase I/II two arm unblinded trial of a modified SGB protocol 
incorporated into Standard of Care vs UNMC standard of care Only for ARDS COVID-19 patients. 
Subjects and/or Legally Authorize Representative (LAR) will be approached while subject is in 
the ICU/progressive care. If subject is unable to participate in the consenting process, the LAR 
will be contact via telephone and/or video chat. Consents will be sent to LAR electronically. PI 
and/or Sub-I will be present for all consenting process regardless is the ICF process takes place 
in person or video digital presence. 
The randomization will be done by using Stratified Permuted Block Randomization in which 
sequential trial participants will be subdivided into the strata as indicated by their age-groups ie; 
40-59, 60-74, 75-85 years and thereafter allocated to study group via block randomization within 
the strata so that the balance between age groups between the two study groups stays close to 
equal throughout the trial.  
 
 
 


SGB IN COVID-19 VERSION 3.0 NOVEMBER 23, 2020 11 
 
Section 5.0 Treatment Plan of Research Design:  
A prospective block randomized phase I/II two arm unblinded trial of a modified SGB protocol 
incorporated into Standard of Care vs UNMC standard of care Only for ARDS COVID-19 
patients. 
 
Sixteen subjects will be enrolled.  Eight in the control arm and eight in the intervention SGB arm.  
Subjects will be identified on the COVID unit. The study will be explained to the subject and if 
the subject wishes to voluntarily participate, the ICF will be signed. If the subject is unable to 
sign consent, the LAR consent will be utilized.  If LAR is not present, an electronic link to the 
consent will be sent to the LAR via email.  
 
The attending proceduralist will perform the SGB in the ICU/progressive care. ICU/progressive 
care nurse will provide patient monitoring and assistance during the procedure. Standard 
monitors and ACLS resuscitative equipment will be immediately available. A norepinephrine 
solution will be at bedside to treat potential hypotension associated with SGB. The SGB 
perineural catheter will be placed using standard sterile technique. Initial perineural bolus 
injection - clonidine 100 mcg, Decadron PF 5mg, and 0.25% bupivacaine 5 ml is delivered. A 
Cadd perineural infusion 0.2% bupivacaine will be initiated at 2ml/hr for 5 days. Acute pain 
service will discontinue infusion and remove the catheter after 5 days. 
 
All adverse events and serious adverse events related to the SGB. All other adverse and serious 
adverse events, including death will be reported per IRB requirements. Laboratory analysis will 
be obtained at baseline (prior to block, baseline) and on day 1, day 3, and day 5. Labs include a 
cytokine panel (TNF-beta, IL-6, and IL-1β), measurements of exhaled nitric oxide levels, and 
CRP (daily). Vital Parameter Analysis: Oxygenation, supplemental oxygen, type of respiratory 
support and need for mechanical ventilation, blood pressure i.e. hypotension requiring 
vasopressors and utilization of ECMO, heart rate, heart rhythm/new dysrhythmias, 
ICU/progressive care length of stay and discharge disposition will be collected from the EMR. 
 
Control group: There will be no sham procedure for the control group.  The control group will 
have nitric oxide levels performed once a day by a member of the research team. Lab draws will 
be drawn at the same frequency as the treatment group. 
Treatment group:  
The treatment group will have a SGB placed by the APS.   
 
Appendix A. Protocol for stellate ganglion blockade in COVID-19 patients.  
 
ICU/progressive care RN will follow Med-27 NM policy for peripheral nerve catheter 
management. APS will utilize a similarly established standard of care in managing the catheters 
daily, for 5 consecutive days. This includes daily rounding on the patient to assess for signs of 
infection, muscle weakness, voice hoarseness, hematoma, intravascular migration, local 
anesthetic systemic toxicity, correct medication verification, verification of pump setting, 
evaluation for Horner’s syndrome (expected), patient education, and proper dressing coverage. 
 


SGB IN COVID-19 VERSION 3.0 NOVEMBER 23, 2020 12 
 
Horner's syndrome refers to a constellation of symptoms that are associated with a stellate 
ganglion block.  These include a decreased pupil size on the affected side, delayed reaction to 
light on the affected side, drooping eyelid and decreased sweating on the affected side.  
Increased temperature and vascular dilation are also noted on the affected side with stellate 
ganglion block.
 
 


SGB IN COVID-19 VERSION 3.0 NOVEMBER 23, 2020 13 
 
Schedule of events: *treatment group only
Assessment 
Screening: 
Visit-1  
Baseline, 
Enrollment,  
Randomization
:  (Day 0) 
Treatment 
Day 1 
Treatment 
Day 2 
Treatment 
Day 3 
Treatment 
Day 4 
Treatment 
Day 5 
EOS  
Discharge 
from 
hospital 
Follow-up: 
Day 90 
Inclusion/Exclusion 
Criteria 
X 
 
 
 
 
 
 
 
 
Informed Consent Form   
X 
  
  
  
  
  
 
  
  
Enrollment/Randomization 
X 
 
 
 
 
 
 
 
 
Demographics 
X 
  
  
  
  
  
 
  
 
Eligibility 
X 
  
  
  
  
  
 
  
 
Medical History  
X 
  
  
  
  
  
 
  
  
Data Collection (Vitals ect) 
X 
X 
X 
X 
X 
X 
X 
X 
 
Acute Pain Service  
 
X* 
X* 
X* 
X*  
X* 
X* 
 
 
Stellate Ganglion Block  
 
X* 
  
  
  
  
 
  
  
CRP 
 
X 
X 
 X 
X  
X 
X 
  
 
TNF-Alpha 
 
X 
X 
 
X 
 
X 
 
 
IL-Beta 
 
X 
X 
 
X 
 
X 
  
 
IL-6 
 
X 
X 
 
X 
 
X 
 
 
Nitric Oxide Level 
 
X 
X 
X 
X 
X 
X 
 
 
Telephone Call  
 
 
 
 
 
 
 
 
X 
Concomitant Medications 
  
X 
X 
X 
X 
X 
X 
X 
X 
Adverse Events  
  
X 
X 
X 
X 
X 
X 
X 
X 


SGB IN COVID-19 VERSION 3.0 NOVEMBER 23, 2020 14 
 
 
 
 
Section 6.0 Measurement of Effect: 
We will be taking measurement of the biomarkers indicative of oxygenation, lung and proinflammatory immune 
response and nitric oxide - specifically,  
a) differences in mean/median values for SGB vs SOC will be assessed at each of the study designated time 
points for all the continuous biomarker measures - by assessing magnitude of difference and its 95% confidence 
level and testing differences for statistical significance at each of the time points;  
b) Differences in mean/median values for SGB vs SOC will be assessed at treatment day 5 - adjusted for baseline 
levels  
c) Differences in changes from baseline levels for SGB vs SOC as measured by comparison in slope trends; 
d) Differences in frequency of adverse events for SGB vs SOC over the study period from treatment through 90 
day of follow up; 
Secondarily,  
e) Differences between SGB vs SOC in frequency and time to occurrence of cardiac arrhythmias; 
f) Differences between SGB vs SOC in frequency of need for and duration of use mechanical ventilation and/or 
extracorporeal membrane oxygenation (ECMO); 
g) Differences between SGB vs SOC in survival experience over treatment period through 90 -day discharge 
follow up  
Sample Size issues: 
For power computations we assume that SGB will particularly have an impact in reduction of inflammatory response 
as measured by IL-6. Looking at a meta-analyses of IL-6 values [Ulhaq ZS, Soraya GV. Interleukin-6 as a potential 
biomarker of COVID-19 progression. Med Mal Infect. 2020;50:382–383. doi: 10.1016/j.medmal.2020.04.002. 
2020/04/08] and picking the largest of studies of COVID patients [Qin C, Zhou L, Hu Z, Zhang S, Yang S, Tao Y, et 
al. Dysregulation of immune response in patients with COVID-19 in Wuhan, China. Clin Infect Dis 2020, 
http://dx.doi.org/10.1093/cid/ciaa248 [pii: ciaa248].], we estimate the overall mean (SD) IL-6 for COVID-19 patients 
to be 21 pg/mL (30.1). Using these estimates we see that a sample of 16 patients equally randomized into SGB (n=8) 
and SoC (n=8) would provide sufficient power to observe magnitude of differences in mean of IL-6 from as small as 
about 50 pg/mL and larger with 80% power at the 5% significance level assuming 2-sided hypothesis testing. (see 
Power Figure). The study [Liu MH, Tian J, Su YP, Wang T, Xiang Q, Wen L. Cervical sympathetic block regulates 
early systemic inflammatory response in severe trauma patients. Med Sci Monitor. 2013;19:194–201.], indicates that 
SGB is capable of eliciting reductions of IL-6 between groups and from baseline of magnitudes of greater than 100 
pg/mL within 72hrs of first injection. 


SGB IN COVID-19 VERSION 3.0 NOVEMBER 23, 2020 15 
 
 
 
 
Section 7.0 Study Parameters:  
  
Baseline Assessments   
• 
Current Fio2/PaO2 ratio   
• 
Current type of ventilation and oxygen use   
• 
Current production of nitric oxide via Niox   
• 
Current blood pressure and heart rate parameters   
• 
Labs: IL-1beta, TNF-alpha, IL-6, ABG, CRP  
• 
Chest x-ray   
• 
Need for mechanical ventilation or other support   
• 
Need for pressure support   
 
Day 1 Assessments     
• 
Vital Signs q 6 hours (0000,0600,1200, 1800)   
• 
FiO2   
• 
PaO2 if available   


SGB IN COVID-19 VERSION 3.0 NOVEMBER 23, 2020 16 
 
• 
Chest x-ray – if available   
• 
Heart rate and any arrhythmias noted via telemetry    
• 
Evidence of successful/ongoing block   
• 
Horner’s syndrome     
• 
Current rate of infusion   
• 
Concomitant Medications   
• 
Vasopressor use   
• 
Adverse Events   
• 
Labs: CRP, IL-1 beta, TNF-alpha, IL-6, ABG (if on vent)  
• 
Production of nitric oxide via Niox   
 
Day 2 Assessments   
• 
Vital Signs q 6 hours (0000,0600,1200, 1800)   
• 
FiO2   
• 
PaO2 if available   
• 
Chest x-ray- if available   
• 
Heart rate and any arrhythmias noted via telemetry   
• 
Blood gas if available   
• 
CRP  
• 
Evidence of successful/ongoing block   
• Horner’s syndrome     
• Current rate of infusion   
• Concomitant Medications   
• Vasopressor use   
• 
Adverse Events   
• 
Production of nitric oxide via Niox   
 
Day 3 Assessments   
• 
Vital Signs q 6 hours (0000,0600,1200, 1800)   
• 
FiO2   
• 
PaO2 if available   
• 
Chest x-ray – if available   
• 
Heart rate and any arrhythmias noted via telemetry    
• 
Evidence of successful/ongoing block   
• 
Horner’s syndrome   
• 
Current rate of infusion   
• 
Concomitant Medications   
• 
Vasopressor use   
• 
Adverse Events   
• 
Labs: Labs: IL-1beta, TNF-alpha, IL-6, ABG (if on vent), CRP   
• 
Production of nitric oxide via Niox   
 
Day 4 Assessments   
• 
Vital Signs q 6 hours (0000,0600,1200, 1800)   
• 
FiO2   
• 
PaO2 if available   
• 
Chest x-ray- if available   
• 
Heart rate and any arrhythmias noted via telemetry   
• 
Blood gas if available   
• 
CRP  


SGB IN COVID-19 VERSION 3.0 NOVEMBER 23, 2020 17 
 
• 
Evidence of successful/ongoing block   
• Horner’s syndrome     
• Current rate of infusion   
• Concomitant Medications   
• Vasopressor use  
• Production of nitric oxide via Niox    
• Adverse Events   
 
Day 5 Assessments   
• Vital Signs q 6 hours (0000,0600,1200, 1800)   
• FiO2   
• PaO2 if available   
• Chest x-ray-if available   
• Heart rate and any arrhythmias noted via telemetry   
• Evidence of successful/ongoing block   
• Horner’s syndrome     
• Current rate of infusion   
• Concomitant Medications   
• Vasopressor use   
• Adverse Events   
• Labs: Labs: IL-1beta, TNF-alpha, IL-6, ABG (if on vent), CRP   
• Production of nitric oxide via Niox    
 
Follow-up assessment Day 90   
• 
Survival status 
• 
SF 36   
• 
Adverse events   
• 
Ongoing issues/oxygen use/rehab   
  
 
Section 8.0 Drug Dosage: 
 
There will be no dosing adjustments to the continuous perineural catheter or initial bolus injection. The bosting of the 
block has been reduced to the minimum effective dose.  
 
SGB Drug doses:  
Initial perineural bolus injection will include clonidine 100 mcg, decadron PF 5mg, and 0.25% bupivacaine 5 ml.  
 
Perineural catheter:  
Infusion of 0.2% bupivacaine will be initiated at 2ml/hr for 5 days.  
 
All medications are FDA approved.  Standard orders for perineural blocks will be entered into the EMR system.  
Pharmacy responsible for ICU/progressive care will dispense orders for the medication used in the SGB.  Pharmacist in 
ICU/progressive care will fill Cadd pump infusion catheter once per day per standard procedure in the ICU/progressive 
care.   
 
Section 9.0 Adverse Event Reporting Guidelines:  
 


SGB IN COVID-19 VERSION 3.0 NOVEMBER 23, 2020 18 
 
The initial procedure will be stopped and the patient will be withdrawn if any of the following occurs; vasopressor or 
unresponsive hypotension, intrathecal injection, pneumothorax, expanding hematoma, allergic reaction, or cardiac 
arrhythmias. For continuous infusions, the catheter will be removed and the patient will be withdrawn if any of the 
following occur: local systemic toxicity, seizure, catheter migration to intravascular or intrathecal space, expanding 
hematoma, vasopressor unresponsive hypotension, symptomatic bradycardia, insertion site infection. Any adverse 
events will be treated with Nebraska Medicine standard of care procedures. Subjects can also voluntarily withdraw at 
any time. The PI can also withdraw any subject that is not felt to be a suitable candidate for the study. 
 
Serious adverse events directly related to block will result in withdrawal. Directly block related serious adverse events 
include: local systemic toxicity, seizure, serious allergic reaction, expanding hematoma, or catheter migration to 
intravascular or intrathecal space, insertion site infection. As well, patients will be withdrawn if the patient develops 
medication unresponsive bradycardia or hypotension. This may not be directly related to block but discontinuation of 
infusion may facilitate resuscitation of patient. Expected complications may include voice hoarseness, ipsilateral eyelid 
drooping, mild pain at site of catheter, and blurred vision. Occurrence of expected complications will not result in 
withdrawal from study unless demanded by the patient. 
 
 
Section 10.0 Statistical Considerations:  
 
Statistical considerations for primary objective, the analysis would include means/medians (standard errors, IQRs) at 
each time point - and also represented by error bars - and comparisons using t test or the Mann-Whitney U test as 
appropriate. Multivariate analyses using Generalized estimating equations (GEE) and to compare longitudinal changes 
in the two groups adjusting for confounders and as well as ANCOVA based regression to measure before and after 
changes. Kaplan-Meier survival methods to measure time to defined thresholds and Cox regression to assess any 
impact of confounders.  
 
For safety - AE’s will be assessed by providing descriptive statistics related to their frequency (summarized by 
occurrence, percentage of occurrence, severity, seriousness, outcome, relation to treatment, start time summary, 
duration of AE analysis) as well as graphically via box plots and cumulative incidence plots indicative of distributions 
in the two trial groups. Non-parametric methods (e.g. Fisher Exact testing) will be used to statistically compare the 
period frequency of events between the two groups. In general, timely analysis, by creating summaries of adverse 
events and other safety measurements such as relevant vital signs, ECG, Laboratory abnormal findings will be done to 
keep a check on the increase in intensity of observations taken at baseline and/or new findings arisen after baseline.  
 
Secondary measures: 
Occurrence of cardiac arrhythmias, need for mechanical ventilation and/or ECMO as well as overall survival will be 
compared using time-to-event based methods (e.g. Kaplan-meier curves). The expectation is that any non-statistically 
significant but implied trends will be evaluated in larger phase IIb /III trial that will follow.  
 
Stopping Rules: 
We have computed stopping rules for safety, from a statistical standpoint, standpoint based on the known background 
rate to help support export opinion. The stopping rules for this study are based on the prospectively accumulated safety 
data collected from each individual patient and utilize the hypothesis testing approach.  The idea is to rule out an 
observed event rate that is higher than the background event rate and to stop the trial if an excessive event rate is 
observed. For our plan to enroll 16 subjects, we assume (based on literature) that the background rate for the known 
risk of our experimental intervention is 10%.   Based on this we have constructed a stopping rule plan (See Table 
below) based on the background rate of the main Serious Adverse Drug Reaction or Event SAE/ADR of 10%. 
 
Our DSMB is empowered to stop the trial whenever they deem fit to protect the safety of patients. However, based on 
our plan, the DSMB will consider adopting a stopping rule that evaluates the rate of SAE/ADR after 5 enrollments, 


SGB IN COVID-19 VERSION 3.0 NOVEMBER 23, 2020 19 
 
and thereafter with each enrollment and SAE/ADR reported will require stopping/suspension of trial entry if the 
observed rate of SAE/ADR is sufficient to reject the null hypothesis that the true SAE/ADR proportion (P) is 10% or 
less in favor of the (one-sided) alternative hypothesis that the true SAE/ADR proportion is more than 10%. The table 
below depicts the stopping guidelines. Exact binomial methods are used to compute the p values and confidence limits. 
One-sided lower 90% confidence limit is calculated. 
Number of 
Subjects 
Enrolled in the 
Study 
Number of 
SAE/ADR Needed 
to Reject Null 
Hypothesis 
Observed 
Rate of 
SAE/ADR 
(%) 
One-
sided p 
values 
Lower 90% 
Confidence 
Limit 
~5 
2 
40% 
0.0815 
11.22% 
6-10 
3 
30% 
0.0702 
11.58% 
11-15 
4 
27% 
0.0556 
12.18% 
16-20 
5 
25% 
0.0432 
12.69% 
Thus, for instance, if 2+ SAE/ADR events are observed in less than and equal to 5 subjects enrolled, the lower 
confidence limit of 11.22% will exceed the 10% background rate. The stopping rule for safety will be triggered and the 
study should be suspended/stopped at the discretion of the DSMB. 
 
Section 11.0 Records to be kept: A list of all records, including flow sheets, data collection forms/instruments, summary 
and evaluation forms will be locked in the study coordinator’s office. The subject list will be maintained by the study 
coordinator. The data from the electronic medical record will be retrieved and entered into the REDCAP database by 
research personnel.   
 
Section 12.0 Patient Consent: The consent form must adhere to the guidelines established by the Institutional Review 
Board of the University of Nebraska Medical Center. The most current version of ICF will be located in the IRB 
application #523-20-FB.  Electronic versions of ICF will be used in the event a LAR is needed to sign consent.  
 
Subjects and/or LAR will be approached while subject is in the ICU/progressive care. If subject is unable to participate 
in the consenting process, the LAR will be contact via telephone and/or video chat. Consents will be sent to LAR 
electronically. PI and/or Sub-I will be present for all consenting process regardless is the ICF process takes place in 
person or video digital presence. 
 
The subject will be in the ICU/progressive care room. A one-on-one conversation will be had between the subject & 
PI/Sub-I, of approximately 30 minutes to review the ICF. Then the subject will be given time alone to read over consent 
and ask any additional questions. If the LAR is not present in the ICU/progressive care, the LAR will be spoken to over 
the telephone. An electronic ICF will be sent to the LAR prior to the phone conversation. The phone conversation will 
last approximately 30 minutes to review the ICF. The LAR will be instructed to hang up and read the ICF in its entirety. 
A return call will be placed to the LAR at a designated time. Additional questions will be answered before electronic 
signature is done by LAR. 
 
 
Section 13.0 Study and Safety monitoring DSMB  
  
A DSMB has been constituted that includes:  Dr. Robert Lobato, Dr. Madhuri Are, and Danstan Bagenda, Ph.D., 
whose responsibility will be to review continually the safety and efficacy data, as well as the other aspects of the trials 


SGB IN COVID-19 VERSION 3.0 NOVEMBER 23, 2020 20 
 
conduct.  The DSMB has been charged with making recommendations regarding early suspension or termination of 
age trial if there is unexpected evidence of safety concerns or dramatic intervention effect.  With this particular phase, 
in addition to proper conduct of the trial as indicated in the protocol the DSMB will primarily  be concerned with 
monitoring  adverse effects and assessing any  potential adverse events with respect to patients  safety at all times  and 
advising study continuation.  The study PI will, nevertheless, still shoulder the responsibility of immediately reporting 
potential severe adverse effects to the DSMB and ultimately all SAEs to the IRB.  Weekly or  immediately - at the 
urgent  earliest opportunity-upon each potential SAE whichever occurs first, the DSMB will review the accumulating 
numbers and types of severe adverse-including  assessing there relatedness to study intervention and recommend any 
analyses by the study  biostatistician-pooled , by treatment group, or disaggregated as  may be requested,   for review  
against the specified stopping rules and to advise any concerns and  course of action with regard to  any individual  of 
collective  patient safety. The DSMB will be supported by Danstan Bagenda,  a trained Biostatistician with long 
experience working with NIH study  DSMBs for phase I, II and III clinical trials, and who, although a Co-I  with the 
study,  has no clinical responsibility  for care with any patients at  UNMC.   
 
Section 13.0 References 
1.Wu C, Chen X, Cai Y, et al. Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in 
Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China [published online ahead of print, 2020 Mar 13]. 
JAMA Intern Med. 2020;180(7):1-11. doi:10.1001/jamainternmed.2020.0994 
 
2.Liu MH, Tian J, Su YP, Wang T, Xiang Q, Wen L. Cervical sympathetic block regulates early systemic 
inflammatory response in severe trauma patients. Med Sci Monit. 2013;19:194-201. Published 2013 Mar 15. 
doi:10.12659/MSM.883833 
 
3. Chen Y, Guo L, Lang H, et al. Effect of a Stellate Ganglion Block on Acute Lung Injury in Septic Rats. 
Inflammation. 2018;41(5):1601-1609. doi:10.1007/s10753-018-0803-x 
 
4. Liu Y, Tao T, Li W, Bo Y. Regulating autonomic nervous system homeostasis improves pulmonary function in 
rabbits with acute lung injury. BMC Pulm Med. 2017;17(1):98. Published 2017 Jul 3. doi:10.1186/s12890-017-0436-0 
 
5. Guo W, Jin XJ, Yu J, et al. Effects of stellate ganglion block on the peri-operative vasomotor cytokine content and 
intrapulmonary shunt in patients with esophagus cancer. Asian Pac J Cancer Prev. 2014;15(21):9505-9509. 
doi:10.7314/apjcp.2014.15.21.9505 
 
6.Na S, Kim OS, Ryoo S, et al. Cervical ganglion block attenuates the progression of pulmonary hypertension via 
nitric oxide and arginase pathways. Hypertension. 2014;63(2):309-315. 
doi:10.1161/HYPERTENSIONAHA.113.01979 
 
7. He,Shunhou, et al. "Effect of stellate block on vasomotor factor, vascular endothelialnitricoxidesynthase and 
pulmonary arterial pressure in rabbits with hypoxic pulmonary artery hypertension." Neural Regeneration Research 2.3 
(2007): 129-133. 
 
8. Åkerström, Sara, et al. "Dualeffect of nitric oxide on SARS-CoVreplication: viral RNA production and 
palmitoylation of the S protein are affected." Virology 395.1 (2009): 1-9. 
 


SGB IN COVID-19 VERSION 3.0 NOVEMBER 23, 2020 21 
 
9. Keyaerts, Els, et al. "Inhibition of SARS-coronavirus infection in vitro by S-nitroso-N-acetylpenicillamine, a nitric 
oxide donor compound." International journal of infectious diseases 8.4 (2004): 223-226. 
 
10. Ferring M, Vincent JL. Is outcome from ARDS related to the severity of respiratory failure?. Eur Respir J. 
1997;10(6):1297-1300. doi:10.1183/09031936.97.10061297 
 
11. Amar D, Zhang H, Roistacher N. The incidence and outcome of ventricular arrhythmias after noncardiac thoracic 
surgery. Anesth Analg. 2002;95(3):. doi:10.1097/00000539-200209000-00006 
 
12. Dyszkiewicz W, Skrzypczak M. Atrial fibrillation after surgery of the lung: clinical analysis of risk factors. Eur J 
Cardiothorac Surg. 1998;13(6):625-628. doi:10.1016/s1010-7940(98)00084-0 
 
13.Shih HT, Webb CR, Conway WA, Peterson E, Tilley B, Goldstein S. Frequency and significance of cardiac 
arrhythmias in chronic obstructive lung disease. Chest. 1988;94(1):44-48. doi:10.1378/chest.94.1.44 
 
14. Jose RJ, Manuel A. COVID-19 cytokine storm: the interplay between inflammation and coagulation. Lancet Respir 
Med. 2020;8(6):e46-e47. doi:10.1016/S2213-2600(20)30216-2 
 
15. Ruan Q, Yang K, Wang W, Jiang L, Song J. Correction to: Clinical predictors of mortality due to COVID-19 based 
on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 2020;46(6):1294-1297. 
doi:10.1007/s00134-020-06028-z 
 
16. Shi S, Qin M, Shen B, et al. Association of Cardiac Injury With Mortality in Hospitalized Patients With COVID-
19 in Wuhan, China [published online ahead of print, 2020 Mar 25]. JAMA Cardiol. 2020;e200950. 
doi:10.1001/jamacardio.2020.0950 
 
17. Guo T, Fan Y, Chen M, et al. Cardiovascular Implications of Fatal Outcomes of Patients With Coronavirus Disease 
2019 (COVID-19) [published online ahead of print, 2020 Mar 27]. JAMA Cardiol. 2020;e201017. 
doi:10.1001/jamacardio.2020.1017 
 
18.Tian Y, Wittwer ED, Kapa S, et al. Effective Use of Percutaneous Stellate Ganglion Blockade in Patients With 
Electrical Storm. Circ Arrhythm Electrophysiol. 2019;12(9):e007118. doi:10.1161/CIRCEP.118.007118 
 
19.Hayase J, Patel J, Narayan SM, Krummen DE. Percutaneous stellate ganglion block suppressing VT and VF in a 
patient refractory to VT ablation. J Cardiovasc Electrophysiol. 2013;24(8):926-928. doi:10.1111/jce.12138 
 
20.Nademanee K, Taylor R, Bailey WE, Rieders DE, Kosar EM. Treating electrical storm : sympathetic blockade 
versus advanced cardiac life support-guided therapy. Circulation. 2000;102(7):742-747. doi:10.1161/01.cir.102.7.742 
 
21.Angus JA, Rajasekaran P, Wright CE. Novel technique to determine the pKA of clonidine at prejunctional α2-
adrenoceptors in cardiac and vascular sympathetic transmission. Eur J Pharmacol. 2017;800:81-95. 
doi:10.1016/j.ejphar.2017.02.030 
 
22.Akers WS, Shah SK, Flynn JD, Apparsundaram S. Effect of clonidine on cardiac norepinephrine spillover in 
isolated rat heart. J Cardiovasc Pharmacol. 2004;43(6):830-838. doi:10.1097/00005344-200406000-00013 
 
23.Romero-Sandoval EA, McCall C, Eisenach JC. Alpha2-adrenoceptor stimulation transforms immune responses in 
neuritis and blocks neuritis-induced pain. J Neurosci. 2005;25(39):8988-8994. doi:10.1523/JNEUROSCI.2995-
05.2005 
 


SGB IN COVID-19 VERSION 3.0 NOVEMBER 23, 2020 22 
 
 
Appendix A.  
 
Protocol for stellate ganglion (SG) blockade in coronavirus disease (covid-19) 
patients  
Purpose:  
To prevent morbidity and mortality related to moderate to severe covid-19 infection.    
Responsibilities:  
The attending intensivists will determine if a covid-19 patient is displaying indications for stellate ganglion block.   
APS will be consulted to urgently place the stellate ganglion block.  
A left sided SGB continuous perineural catheter will be placed by either ultrasound guided or fluoroscopy guided technique 
at the discretion of the APS attending in consultation with the chronic pain attending.   
Procedure:  
The attending proceduralist and resident assistant will perform the SGB at bedside under the following conditions:  
1. 
The block will only be performed in the intensive care setting.   
2. 
Intensive care nurse will provide patient monitoring and assistance during the procedure.   
3. 
The proceduralist will exam and record pupillary size prior to procedure and 20 minutes post injection.  
4. 
For fluoroscopy guidance, the radiology technician will provide imaging assistance during the procedure.   
5. 
A Logiq R7 machine will be brought to the patient’s bedside by the APS attending for ultrasound guidance.  
6. 
All equipment will be decontaminated with bactericidal/virocidal wipes prior to exiting the patient’s room and 
immediately upon exiting the room.   
7. 
Personnel involved in the procedure will don and doff N-95 respirators, gowns, gloves, and faces shields and 
strictly adhere to Nebraska Medicine covid-19 isolation/precautions for this non-aerosol generating bedside 
procedure.  
8. 
Standard ASA monitors and ACLS resuscitative equipment will be immediately available.   
9. 
A norepinephrine solution will be ordered by proceduralist and at bedside in order to treat potential 
hypotension associated with SGB especially in a baseline unstable patient.   
10. 
Pain provider will also bring standard prn IV bolus vasopressors including phenylephrine and epinephrine.  
The SGB perineural catheter will be placed using standard sterile technique.   
1. 
Initial perineural bolus injection will include clonidine 100 mcg, decadron PF 5mg, and 0.25% bupivacaine 5 ml.   
2. 
A Cadd perineural infusion 0.2% bupivacaine will be initiated at 2ml/hr for 5 days.   
3. 
The proceduralist will stay at the patient’s bedside for 20 minutes to monitor for signs of cardiovascular 
instability of respiratory distress. Following this period, the patient may be returned to standard ICU/PROGRESSIVE 
CARE reassessment regimens.    
4. 
The patient will be monitored for neck hematoma formation by the nurse with neck soft tissue reassessment 
every 15 min for 1 hour.   
5. 
APS providers will round on the patient daily and provide standard perineural catheter maintenance as well as 
record of pupillary size.   
6. 
APS will discontinue and remove the catheter after 5 days have elapsed.   
  
 
 
 
 
 
 
 
 
 


SGB IN COVID-19 VERSION 3.0 NOVEMBER 23, 2020 23 
 
Appendix. B 
SF-36 QUESTIONNAIRE 
 
Name: 
 
 
ID#:   
 
Ref. Dr:  
 
 
Age:   
 
Date: 
 
Gender: M / F 
 
Please answer the 36 questions of the Health Survey completely, honestly, and without interruptions. 
 
GENERAL HEALTH: 
In general, would you say your health is: 
  Excellent 
Very Good 
Good 
Fair 
Poor 
Compared to one year ago, how would you rate your health in general now? 
Much better now than one year ago 
Somewhat better now than one year ago 
About the same 
Somewhat worse now than one year ago 
Much worse than one year ago 
 
LIMITATIONS OF ACTIVITIES: 
The following items are about activities you might do during a typical day. Does your health now limit you in these 
activities? If so, how much? 
 
Vigorous activities, such as running, lifting heavy objects, participating in strenuous sports. 
Yes, Limited a lot 
Yes,  Limited a Little 
No, Not Limited at all 
Moderate activities, such as moving a table, pushing a vacuum cleaner, bowling, or playing golf 
Yes, Limited a Lot 
Yes,  Limited a Little 
No, Not Limited at all 
Lifting or carrying groceries 
Yes, Limited a Lot 
Yes,  Limited a Little 
No, Not Limited at all 
Climbing several flights of stairs 
Yes, Limited a Lot 
Yes,  Limited a Little 
No, Not Limited at all 
Climbing one flight of stairs 
Yes, Limited a Lot 
Yes,  Limited a Little 
No, Not Limited at all 
Bending, kneeling, or stooping 
Yes, Limited a Lot 
Yes,  Limited a Little 
No, Not Limited at all 
Walking more than a mile 
Yes, Limited a Lot 
Yes,  Limited a Little 
No, Not Limited at all 


SGB IN COVID-19 VERSION 3.0 NOVEMBER 23, 2020 24 
 
Walking several blocks 
Yes, Limited a Lot 
Yes,  Limited a Little 
No, Not Limited at all 
Walking one block 
       Yes,  Limited a Lot 
Yes,  Limited a Little 
No, Not Limited at all 
Bathing or dressing yourself 
Yes, Limited a Lot 
Yes,  Limited a Little 
No, Not Limited at all 
PHYSICAL HEALTH PROBLEMS: 
During the past 4 weeks, have you had any of  the following problems with your work or other regular daily 
activities as  a result of your physical health? 
 
Cut down the amount of time you spent on work or other activities 
Yes 
No 
Accomplished less than you would like 
Yes 
No 
Were limited in the kind of work or other activities 
Yes 
No 
Had difficulty performing the work or other activities (for example, it took extra effort) 
Yes 
No 
 
EMOTIONAL HEALTH PROBLEMS: 
During the past 4 weeks, have you had any of the following problems with your work or other regular daily 
activities as  a result of any emotional problems (such as feeling depressed or anxious)? 
 
Cut down the amount of time you spent on work or other activities 
Yes 
No 
Accomplished less than you would like 
Yes 
No 
Didn't do work or other activities as carefully as usual 
Yes 
No 
SOCIAL ACTIVITIES: 
Emotional problems interfered with your normal social activities with family, friends, neighbors, or groups? 
 
Not at all 
Slightly 
Moderately 
Severe 
Very Severe 
 
PAIN: 
How much bodily pain have you had during the past 4 weeks? 
 
None 
Very Mild 
Mild 
Moderate 
Severe 
Very Severe 


SGB IN COVID-19 VERSION 3.0 NOVEMBER 23, 2020 25 
 
During the past 4 weeks, how much did pain interfere with your normal work (including both work outside the 
home and housework)? 
 
Not at all 
A little bit 
Moderately 
Quite a bit 
Extremely 
 
ENERGY AND EMOTIONS: 
These questions are about how you feel and how things have been with you during the last 4 weeks. For each 
question, please give the answer that comes closest to the way you have been feeling. 
 
Did you feel full of pep? 
All of the time 
Most of the time 
A good Bit of the Time 
Some of the time 
A little bit of the time 
None of the Time 
 
Have you been a very nervous person? 
All of the time 
Most of the time 
A good Bit of the Time 
Some of the time 
A little bit of the time 
None of the Time 
 
Have you felt so down in the dumps that nothing could cheer you up? 
All of the time 
Most of the time 
A good Bit of the Time 
Some of the time 
A little bit of the time 
None of the Time 
 
Have you felt calm and peaceful? 
All of the time 
Most of the time 
A good Bit of the Time 
Some of the time 
A little bit of the time 
None of the Time 
 
Did you have a lot of energy? 
All of the time 
Most of the time 
A good Bit of the Time 
Some of the time 
A little bit of the time 


SGB IN COVID-19 VERSION 3.0 NOVEMBER 23, 2020 26 
 
None of the Time 
 
Have you felt downhearted and blue? 
All of the time 
Most of the time 
A good Bit of the Time 
Some of the time 
A little bit of the time 
None of the Time 
 
Did you feel worn out? 
All of the time 
Most of the time 
A good Bit of the Time 
Some of the time 
A little bit of the time 
None of the Time 
 
Have you been a happy person? 
All of the time 
Most of the time 
A good Bit of the Time 
Some of the time 
A little bit of the time 
None of the Time 
 
Did you feel tired? 
All of the time 
Most of the time 
A good Bit of the Time 
Some of the time 
A little bit of the time 
None of the Time 
 
 
 
 
 
 
 
SOCIAL ACTIVITIES: 
During the past 4 weeks, how much of the time has your physical health or emotional problems interfered with 
your social activities (like visiting with friends, relatives, etc.)? 
 
All of the time 
Most of the time 
Some of the time 
A little bit of the time 


SGB IN COVID-19 VERSION 3.0 NOVEMBER 23, 2020 27 
 
None of the Time 
 
GENERAL HEALTH: 
How true or false is each of the following statements for you? 
 
I seem to get sick a little easier than other people 
Definitely true 
Mostly true 
Don't know 
Mostly false 
Definitely false 
I am as healthy as anybody I know 
Definitely true 
Mostly true 
Don't know 
Mostly false 
Definitely false 
I expect my health to get worse 
Definitely true 
Mostly true 
Don't know 
Mostly false 
Definitely false 
My health is excellent 
Definitely true 
Mostly true 
Don't know 
Mostly false 
Definitely false
 

ICF_001.pdf: 
 
 
 
Stellate Ganglion Blockade in COVID-19 Positive Patients 
NCT04445337 
01 Oct 2020 


PT NAME: 
MR#: 
IRBVersion 1 
IRB Approved 
Valid until 10/01/2021 
 
 
CONSENT FORM 
IRB PROTOCOL # 0523-20-FB 
Page 1 of 9 
CONSENT FORM 
Adult/LAR-Clinical Biomedical 
Title of this Research Study 
Stellate Ganglion Blockade for COVID-19 Positive Patients 
 
Invitation and Summary 
 
You are invited to be in this research study. Taking part in this research is voluntary. 
You do not have to take part. For the purposes of this document: "You" can refer to: 
Yourself 
The person for whom you are the Legally Authorized Representative (LAR) 
Your child under the age of 19. 
"Organization" can refer to: University of Nebraska Medical Center (UNMC), 
Nebraska Medicine (NM), University of Nebraska at Omaha (UNO) or Children's 
Hospital & Medical Center (CH&MC). 
 
Here is a summary of the purpose, methods, risks, benefits, and alternatives, to help 
you decide whether or not to take part in the research. 
 
You are invited to be in this research study because you have COVID-19 and you are 
having breathing problems. 
 
The purpose of this research study is to see whether a stellate ganglion block (SGB) 
is safe in patients with breathing problems due to COVID. 
 
The SGB involves placing a small tube into the front of your neck, toward nerves at 
the back of your neck. This is done with the help of an x-ray machine or ultrasound 
device. The tube is left in place so you can get medication thru it for five days. Then 
the tube is taken out. 
 
Researchers will collect information from your chart every day about your oxygen 
levels and breathing problems. Extra blood samples will be collected on days 1 and 
5. 
You will continue to get all the usual care for your COVID infection. 
Risks include bruising, bleeding, swelling at the injection site, collapsed lung 
(pneumothorax), numbness of the arm or shoulder (brachial plexus block), numbness 
of the belly, hips or legs (spinal or epidural block), decreased heart rate, decreased 
rate of breathing (high spinal anesthetic), numbed or weakness in your hands or feet 
(nerve damage). 


PT NAME: 
MR#: 
IRBVersion 1 
IRB Approved 
Valid until 10/01/2021 
 
 
The medicine given through the tube might improve your breathing. 
 
Instead of being in the research you can get the usual care for your COVID infection. 
CONSENT FORM 
IRB PROTOCOL # 0523-20-FB 
Page 2 of 9 
 
 
 
Why are you being asked to be in this research study? 
You are being asked to participate in this study because you are COVID-19 positive, 
experiencing breathing related symptoms, and between the age of 40-85 years old. 
In COVID-19, research has shown our bodies response to the virus has an effect on 
the heart and lungs. The stellate ganglia is a part of a collection of nerves located 
near your neck just to the side of your windpipe. 
 
What is the reason for doing this research study? 
The reason this research is being done is to determine if SGB are safe and useful in 
treating COVID-19 positive patients who have heart and lung symptoms. 
 
What will be done during this research study? 
There will be up to 16 research participants enrolled in this study at UNMC/Nebraska 
Medicine. 
 
You will be randomly assigned (like a flip of a coin) to one of two groups. An equal 
number of patients will be assigned to each research group. 
 
If you are in the EXPERIMENTAL group, you will have the block placed in the ICU. 
The block will be placed on the left or right side of your neck under ultrasound or with 
fluoroscopy (a video x-ray). Ultrasound involves a probe on your neck and taking 
sound wave pictures of your body through your neck. The medication used for the 
block are clonidine 100 mcg, Decadron PF 5mg and 0.25% bupivacaine 5 mL. This 
medication will be administered once during the block. These medications are 
approved by the Food and Drug Administration (FDA). The intensive care nurse will 
monitor your vital signs during the block. You will be monitored every 15 minutes for 
1 hour after the block is placed. The Acute Pain Service Team will follow you for in 
the ICU for 5 days. The catheter placed will be used to deliver 0.2% bupivacaine at 
2mL/hour for 5 days. The small tube that will be placed will be removed after 5 days. 
 
If you are in the STANDARD group, you will be treated as if you were not in the 
research. You will only have the lab studies and data collected from your electronic 
medical record (EMR). Labs will be done on the first day, third day and fifth day. We 
will collect about 1-2 teaspoons of blood. 


PT NAME: 
MR#: 
IRBVersion 1 
IRB Approved 
Valid until 10/01/2021 
 
 
CONSENT FORM 
IRB PROTOCOL # 0523-20-FB 
Page 3 of 9 
All subjects will have data collected including: clinical outcomes (type of oxygen 
used, blood pressure and heart rate, chest x-ray and types of medications used. 
 
All patients will have lab studies completed on Day 1, Day3, and Day 5. The 
sample(s) we collect will not be used for other research studies by us, or by any other 
investigator after this research is over. 
 
Blood draws will be done on Day 1, Day 3, and Day 5. Each blood draw will be about 
15 mL of blood or equal to about 1 tablespoon. Lab studies include; C-Reactive 
Protein (CRP), Cytokine Panel (Tumor Necrosis Factor-Alpha, Interleukin 6, 
Interleukin beta). These are commonly used blood test to measure the inflammatory 
markers in blood. 
 
What are the possible risks of being in this research study? 
Both EXPERIMENTAL and STANDARD Group: 
For this study, we plan to take 15mL at each blood draw, which is equal to 1 
tablespoon. You may feel a slight needle prick when we draw your blood. Some 
people may have a small bruise that will go away in a day or two. Sometimes, people 
feel light headed or faint. There is also a rare chance of infection with the blood draw. 
 
EXPERIMENTAL Group Only: 
Potential risks involved for the SGB block include: bruising, bleeding, swelling at the 
injection site, collapsed lung (pneumothorax), numbness of the arm or shoulder 
(brachial plexus block), numbness of the belly, hips or legs (spinal or epidural block), 
decreased heart rate, decreased rate of breathing (high spinal anesthetic), numbed 
or weakness in your hands or feet (nerve damage). 
 
You could potentially have an allergic reaction to some of the medication that will be 
given with the stellate ganglion block. The medications being used are not a common 
cause of allergic reactions and are used routinely in patients who are very sick. 
 
Risks of bupivacaine & Decadron medications include; allergic reaction, adrenal 
suppression (body aches, fatigue), increase of blood sugar levels. Risks of clonidine 
medication; allergic reaction, decreased blood pressure. There will be certain 
medications available that the doctor will administer in the event that you do have an 
allergic reaction. If your blood pressure does get low, the doctor will give you 
medication to help increase it. 
 
You could also experience a higher level of sugar in your blood, which should go 
away on its own. The organ that sits on top of your kidneys (adrenal glands) may also 


PT NAME: 
MR#: 
IRBVersion 1 
IRB Approved 
Valid until 10/01/2021 
 
 
CONSENT FORM 
IRB PROTOCOL # 0523-20-FB 
Page 4 of 9 
slow down, which could place you at greater risk of becoming sick. The doctor will 
have medication that he/she can give you if the organs that sit on your kidneys 
(adrenal glands) do slow down. 
 
To reduce your risk the block will be placed using either real-time video images 
(fluoroscopy) or direct images using sound waves to produce pictures of the inside of 
the body (ultrasound). If fluoroscopy is used, there is a possible radiation risk of the 
procedure. You will be closely watched during the procedure using blood pressure, 
heart rate and oxygen monitors. Procedural and nursing staff will monitor you 
throughout the procedure and immediately after for 1 hour. You will remain on the 
heart monitor during the procedure and for 5 days after, while on the continuous local 
numbing medication. 
 
If you experience any serious side effects such as severe low blood pressure, high 
spinal anesthetic, pneumothorax, bleeding, cardiac arrhythmia during the procedure, 
or allergic reaction develop, the procedure will be stopped and you will be withdrawn 
from the study. 
 
What are the possible benefits to you? 
You may not get any benefit from being in this research study. 
 
If you are randomly assigned to the EXPERIMENTAL group there may be potential 
benefits of reducing injury or damage to your body, improving lung function, and 
reducing heart complications. 
 
What are the possible benefits to other people? 
If the results of this study are positive, future patients may benefit from the 
knowledge gained by this study. 
 
What are the alternatives to being in this research study? 
Instead of being in this research study, you can choose not to take part. If you do not 
participate in this study, the care you will receive in the intensive care unit will not 
change. 
 
What will being in this research study cost you? 
There is no cost to you to be in this research study. 
 
Will you be paid for being in this research study? 
You will not be paid to be in this research study. 


PT NAME: 
MR#: 
IRBVersion 1 
IRB Approved 
Valid until 10/01/2021 
 
 
CONSENT FORM 
IRB PROTOCOL # 0523-20-FB 
Page 5 of 9 
Who is paying for this research? 
UNMC Nebraska Neuroscience Alliance COVID-19 Rapid Response Grants gives us 
money to do this study. 
 
What should you do if you are injured or have a medical problem during this 
research study? 
Your health and safety is our main concern. If you are injured or have a medical 
problem because of this study call someone listed at the end of this consent form. 
You can get emergency medical treatment at Nebraska Medicine. You can also go to 
your doctor, the nearest emergency room or call 9-1-1. 
 
We have no plans to pay for your treatment or give you any other money or 
compensation. Your insurance may pay. If they do not you will have to pay. 
 
Signing this consent form does not mean you have given up any of your legal rights. 
 
How will information about you be protected? 
In the course of this research we may collect information about you. This can be 
things that could be used to find out who you are (like your name, phone number, 
birthdate, address). We call this "identifiable private information". We will keep this 
information as confidential as possible. 
The information will not be used for other research by us, or by any other researcher. 
 
Who can see information about you? 
We also will get medical information about you (like medical record number, medical 
history, or the results of physical exams, blood tests, x-rays or other medical or 
research procedures). We call this "protected health information" or PHI. PHI is 
protected by a law called the HIPAA Privacy Rule. We will collect the smallest 
amount of PHI that we can. We will keep your PHI as confidential as possible. 
 
By signing this consent form, you are letting us (the researchers listed on this 
consent form and other people involved in this research at the Organization) have 
access to your PHI. Your PHI will be used only for the purposes described in the 
section "What is the reason for doing this research study?" 
 
You can change your mind and tell us to stop collecting your PHI for use in this 
research at any time by writing to the principal investigator. We can still use the PHI 
we have already collected. If you tell us to stop collecting your PHI, you will have to 
stop being in this research. 


PT NAME: 
MR#: 
IRBVersion 1 
IRB Approved 
Valid until 10/01/2021 
 
 
CONSENT FORM 
IRB PROTOCOL # 0523-20-FB 
Page 6 of 9 
We may share your PHI with the following groups: 
 The UNMC Institutional Review Board (IRB) 
 Institutional officials designated by the UNMC IRB 
 The HHS Office for Human Research Protections (OHRP) 
 
We may also share your PHI with other groups listed below. The HIPAA Privacy Rule 
requires these groups to protect your PHI. 
 The Food and Drug Administration (FDA) 
 Your health insurance company 
 
You are letting us use and share your research data for as long as the research is 
going on. 
 
How will results of the research be made available to you during and after the 
study is finished? 
In most cases, the results of the research can be made available to you when the 
study is completed, and all the results are analyzed by the investigator or the sponsor 
of the research. The information from this study may be published in scientific 
journals or presented at scientific meetings, but your identity will be kept strictly 
confidential. 
 
If you want the results of the study, contact the Principal Investigator at the phone 
number given at the end of this form or by writing to the Principal Investigator at the 
following address: 
 
Michael Lankhorst, MD 
Department of Anesthesiology 
University of Nebraska Medical Center 
986890 Nebraska Medical Center 
Omaha, NE 68198-6890 
402-596-4200 
 
What will happen if you decide not to be in this research study? 
You can decide not to be in this research study. Deciding not to be in this research 
will not affect your medical care or your relationship with the investigator or the 
organization. Your doctor will still take care of you and you will not lose any benefits 
to which you are entitled. 
 
What will happen if you decide to stop participating once you start? 
You can stop being in this research (withdraw) at any time. Just call the researcher or 


PT NAME: 
MR#: 
IRBVersion 1 
IRB Approved 
Valid until 10/01/2021 
 
 
CONSENT FORM 
IRB PROTOCOL # 0523-20-FB 
Page 7 of 9 
any research staff. 
If you stop being in the research study it will not affect your care or your relationship 
with the investigator or the organization. You will not lose any benefits to which you 
are entitled. 
 
Will you be given any important information during the study? 
We will tell you right away if we get any new information that might make you change 
your mind about being in the study. 
 
What should you do if you have any questions about the study? 
We gave you a copy of "What Do I Need to Know Before Being in a Research 
Study?" 
 
If you ever have any questions about this study, call the Principal Investigator or 
anyone else listed on this consent form. 
 
What are your rights as a research participant? 
You have rights as a research subject. These rights have been explained in this 
consent form and in The Rights of Research Subjects that you have been given. If 
you have any questions concerning your rights, or want to discuss problems, 
concerns, obtain information or offer input, or make a complaint about the research, 
you can contact any of the following: 
 The investigator or other study personnel 
 Institutional Review Board (IRB) 
Telephone: (402) 559-6463 
Email: IRBORA@unmc.edu 
Mail: UNMC Institutional Review Board, 987830 Nebraska Medical 
Center, Omaha, NE 68198-7830 
 Research Subject Advocate 
Telephone: (402) 559-6941 
Email: unmcrsa@unmc.edu 
 
 
Documentation of informed consent 
You are deciding whether to be in this research study. Signing means that: 
 You have read and understood this consent form. 
 You have had the consent form explained to you. 
 You have been given a copy of The Rights of Research Subjects 
 You have had your questions answered. 
 You have decided to be in the research study. 


PT NAME: 
MR#: 
IRBVersion 1 
IRB Approved 
Valid until 10/01/2021 
 
 
CONSENT FORM 
IRB PROTOCOL # 0523-20-FB 
Page 8 of 9 
 You have been told you can talk to one of the researchers listed below on this 
consent form if you have any questions during the study. 
 You will be given a signed and dated copy of this consent form to keep. 
 
 
Signature of Subject 
Date 
 
 
Signature of LAR 
Date 
 
 
My signature certifies that all the elements of informed consent described on this 
consent form have been explained fully to the subject/LAR. In my judgment, the 
subject/LAR possesses the legal capacity to give informed consent to participate in 
this research and is voluntarily and knowingly giving informed consent to participate. 
 
Signature  of  Person  Obtaining  Consent 
 
Date 
 
 
Authorized Study Personnel 
Principal 
* Lankhorst, Michael 
phone: 402-516-6336 
alt #: 402-559-4081 
degree: MD 
 
Secondary 
* Heiser, Nicholas 
phone: 402-559-4175 
alt #: 402-559-4081 
degree: MD 
 
* Kassel, Cale 
phone: 402-559-4081 
alt #: 402-559-4081 
degree: MD 
 
* Ladd, Marshall 
phone: 402-559-4081 
alt #: 402-550-4081 
degree: DO 
* Lisco, Steven 
phone: 402-559-5780 
alt #: 402-559-5780 
degree: MD 
 
* Nicholas, Thomas 
alt #: 402-888-2140 
degree: MD 
 
Lead Coordinator 


PT NAME: 
MR#: 
IRBVersion 1 
IRB Approved 
Valid until 10/01/2021 
 
 
CONSENT FORM 
IRB PROTOCOL # 0523-20-FB 
Page 9 of 9 
Hoffman, Julie (Julie) 
phone: 402-559-8299 
alt #: 402-559-8299 
degree: RN BSN 
 
Other Coordinator 
Sindt, Lace 
alt #: 402-559-4081 
degree: RN 


 
This sheet will help you think of questions to ask the investigator or his/her 
staff. You should know all these answers before you decide about being in the 
research. 
Institutional Review Board (IRB) 
What Do I Need To Know 
Before Being In A Research Study? 
You have been invited to be in a research study. Research studies are also called 
"clinical trials" or "protocols." Research is an organized plan designed to get new 
knowledge about a disease or the normal function of the body. The people who are in 
the research are called research subjects. The investigator is the person who is 
running the research study. You will get information from the investigator and the 
research team, and then you will be asked to give your consent to be in the 
research. 
 
 
What is the purpose of the research? Why is the investigator doing the research? 
What are the risks of the research? What bad things could happen? 
What are the possible benefits of the research? How might this help me? 
 
How is this research different than the care or treatment I would get if I wasn t in 
the research? Are there other treatments I could get? 
 
Does everyone in this research study get the same treatment? 
Will being in the research cost me anything extra? 
Do I have to be in this research study? Will the doctor still take care of me if I say no? 
Can I stop being in the research once I ve started? How? 
Who will look at my records? 
 
How do I reach the investigator if I have more questions? 
 
Who do I call if I have questions about being a research subject? 
 
Make sure all your questions are answered before you decide whether or not to 
be in this research. 
 
 
 
 
 
 
Academic Research & Services Building 3000 / 987830 Nebraska Medical Center / Omaha NE 68198-7830 
402-559-6463 / FAX 402-559-3300 / Email: irbora@unmc.edu / http://www.unmc.edu/irb 


 
Institutional Review Board (IRB) 
THE RIGHTS OF RESEARCH SUBJECTS 
AS A RESEARCH SUBJECT YOU HAVE THE RIGHT 
 
to be told everything you need to know about the research before you are 
asked to decide whether or not to take part in the research study. The research 
will be explained to you in a way that assures you understand enough to decide 
whether or not to take part. 
 
to freely decide whether or not to take part in the research. 
 
to decide not to be in the research, or to stop participating in the research at 
any time. This will not affect your medical care or your relationship with the 
investigator or the Nebraska Medical Center. Your doctor will still take care of you. 
 
to ask questions about the research at any time. The investigator will answer 
your questions honestly and completely. 
 
to know that your safety and welfare will always come first. The investigator will 
display the highest possible degree of skill and care throughout this research. Any 
risks or discomforts will be minimized as much as possible. 
 
to privacy and confidentiality. The investigator will treat information about you 
carefully, and will respect your privacy. 
 
... to keep all the legal rights you have now. You are not giving up any of your 
legal rights by taking part in this research study. 
 
to be treated with dignity and respect at all times 
 
The Institutional Review Board is responsible for assuring that your rights and 
welfare are protected. If you have any questions about your rights, contact the 
Institutional Review Board at (402) 559-6463. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Academic Research & Services Building 3000 / 987830 Nebraska Medical Center / Omaha NE 68198-7830 
402-559-6463 / FAX 402-559-3300 / Email: irbora@unmc.edu / http://www.unmc.edu/irb