Investigating Differences in Flare Reaction Incidence and Intensity Following Trigger Finger Injections Using Betamethasone and Methylprednisolone
Phase: PHASE4
Conditions: Trigger Finger
Sponsor: West Virginia University

 
Protocol: 
 
Investigating Differences in Flare Reaction Incidence and Intensity Following 
Trigger Finger Injections Using Betamethasone and Methylprednisolone 
 
 
NCT04900220 
 
April 22, 2021 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

         Investigator Initiated Protocol 
Investigator Resources 
 
 
WVU+kc Protocol #: 2103263450 
PI: Shafic Sraj 
 
Protocol Number & Study Protocol Title 
 2103263450:  Investigating Differences in Flare Reaction Incidence and Intensity Following Trigger 
Finger Injections Using Betamethasone and Methylprednisolone 
 
Abbreviations List 
VAS: Visual Analog Scale 
 
Section I: Team and Research Summary 
 
Study Team Composition 
Principal Investigator –  
Dr. Shafic Sraj: ssraj@hsc.wvu.edu 
 
Co-Investigator(s) –  
Dr. Andrea Lese: andrea.lese@hsc.wvu.edu 
Dr. Joseph Prudhomme: joe.prudhomme@hsc.wvu.edu 
Dr. John Taras: john.taras@hsc.wvu.edu 
 
Study Personnel –  
Emily Ellis: eellis@hsc.wvu.edu 
Jennifer Eicher: jeicher@hsc.wvu.edu 
Anthony Siler: afs0020@hsc.wvu.edu 
Kareem Wasef: kw0045@mix.wvu.edu 
Nikolas Tasser: nikolas.tasser@wvumedicine.org 
Research Summary 
Study Population –  
80-100 patients to be recruited.  
Inclusion Criteria: 
Adult 
Single trigger injection 
First time for the digit 
No prior surgery on digit 
Exclusion Criteria: 
Current oral steroid use 
Rheumatoid arthritis 
                      More than one single digit involved 
                     Previous injection in same digit 
                     Prior surgery on same digit 
                     Other injections in the same clinic on the same day 
 

         Investigator Initiated Protocol 
Investigator Resources 
 
 
WVU+kc Protocol #: 2103263450 
PI: Shafic Sraj 
Study Design – The two standard of care corticosteroids used for trigger finger treatment are 
betamethasone and methylprednisolone. Both injections are effective in treating trigger finger and 
the decision of which to use in treatment is currently a matter of the current practice and physician 
preference. There is no literature comparing the side effects, specifically flare reactions between 
these two treatments. Our goal through this randomized trial is to see whether there is a difference 
between these two corticosteroids in inducing flare reactions and if there are any differences in the 
peak level of pain and its duration. We will carry out a double-blinded randomized trial enrolling 
patients into one of the two treatment groups. The volume of the doses of steroid to be given will be 
standardized to 1 cc of either methylprednisolone (40 mg) or betamethasone (6 mg). We will instruct 
patients who meet the inclusion criteria to complete a visual analog scale (VAS) of their pain (1-10) 
prior to the injection, immediately after the injection, five minutes after the injection, and once a day 
for a minimum of 7 days after the injection. The incidence, intensity, time to peak and time to 
resolution of the flare reactions (defined as a 2-point increase from pre-injection pain) will be 
assessed and compared between the two groups. Findings indicating a statistically significant 
difference in the incidence and/or intensity of the flare reactions would be clinically significant and 
would be evidence supporting the switch of current standard practice to one corticosteroid over the 
other. Patients will only receive a single, standard of care, trigger finger injection on the day they 
present to the clinic. The next 7 days, up to two weeks if needed, of follow-up will only be a single 
short survey question to determine pain level. 
Patients will be identified by the surgeon on the day they present to clinic, and will be recruited and 
consented by the study personnel. Data will be collected from the patient and stored in the REDCap 
server. There is not more than minimal risk involved. 
 
Study Duration –  
Enrollment: could take up to a year, depending on how long it takes to recruit enough patients. 
Data Collection: 3-6 months after conclusion of patient enrollment 
Analysis: 3-6 months after conclusion of data collection 
 
Section II: Design 
 
Background & Significance  
Corticosteroid injections are effective non-surgical approach to treating trigger finger (stenosing 
tenosynovitis) with success rates reported as high as 92% after just one injection [1]. Among their side 
effects is a post-injection flare of increased pain that is attributed to crystal-induced synovitis [2]. 
Reports of these flares in the literature have been rare. Recent evidence their incidence can be as high 
as 33% [3]. We feel they are a more common clinical issue than traditionally reported and it would be 
beneficial to control and reduce their incidence if possible.  
 
Two common corticosteroids used for trigger finger treatment are betamethasone and 
methylprednisolone [4][5]. Both injections are effective in treating trigger finger and the decision of 
which to use in treatment is currently a matter of the current practice and physician preference. 
There is no literature comparing the side effects, specifically flare reactions between these two 
treatments. Our goal through this randomized trial is to see whether there is a difference between 

         Investigator Initiated Protocol 
Investigator Resources 
 
 
WVU+kc Protocol #: 2103263450 
PI: Shafic Sraj 
 
Objectives 
Two common corticosteroids used for trigger finger treatment are betamethasone and 
methylprednisolone. Both injections are effective in treating trigger finger and the decision of which 
to use in treatment is currently a matter of the current practice and physician preference. There is no 
literature comparing the side effects, specifically flare reactions between these two treatments. Our 
goal through this randomized trial is to see whether there is a difference between these two 
corticosteroids in inducing flare reactions and if there are any differences in the peak level of pain and 
their duration.  
Findings indicating a statistically significant difference in the incidence and/or intensity of the flare 
reactions would be clinically significant and would be evidence supporting the switch of current 
practice to one corticosteroid over the other. 
 
 
Study Design & Methodology 
The two standard of care corticosteroids used for trigger finger treatment are betamethasone and 
methylprednisolone. Both injections are effective in treating trigger finger and the decision of which 
to use in treatment is currently a matter of the current practice and physician preference. There is no 
literature comparing the side effects, specifically flare reactions between these two treatments. Our 
goal through this randomized trial is to see whether there is a difference between these two 
corticosteroids in inducing flare reactions and if there are any differences in the peak level of pain and 
its duration. We will carry out a double-blinded randomized trial enrolling patients into one of the two 
treatment groups. The volume of the doses of steroid to be given will be standardized to 1 cc of either 
methylprednisolone (40 mg) or betamethasone (6 mg). We will instruct patients who meet the 
inclusion criteria to complete a visual analog scale (VAS) of their pain (1-10) prior to the injection, 
immediately after the injection, five minutes after the injection, and once a day for a minimum of 7 
days after the injection. The incidence, intensity, time to peak and time to resolution of the flare 
these two corticosteroids in inducing flare reactions and if there are any differences in the peak level 
of pain and their duration.  
 
We will carry out a double-blinded randomized trial enrolling patients into one of the two treatment 
groups. The volume of the doses will be standardized to 1 cc of either methylprednisolone (40 mg) or 
betamethasone (6 mg).  We will instruct patients who meet the inclusion criteria to complete a visual 
analog scale (VAS) of their pain (1-10) prior to the injection, during the injection and once a day for 
the following 7 days after the injection. We estimate that we need a minimum of 30 patients in each 
group to achieve a minimum of 80% power and 0.05 significance. The incidence, intensity, time to 
peak and time to resolution of the flare reactions (defined as a 2-point increase from pre-injection 
pain [3]) will be assessed and compared between the two groups. Findings indicating a statistically 
significant difference in the incidence and/or intensity of the flare reactions would be clinically 
significant and would be evidence supporting the switch of current practice to one corticosteroid over 
the other. 
 
REFERENCES: See References section 
 

         Investigator Initiated Protocol 
Investigator Resources 
 
 
WVU+kc Protocol #: 2103263450 
PI: Shafic Sraj 
reactions (defined as a 2-point increase from pre-injection pain) will be assessed and compared 
between the two groups. Findings indicating a statistically significant difference in the incidence 
and/or intensity of the flare reactions would be clinically significant and would be evidence supporting 
the switch of current standard practice to one corticosteroid over the other. Patients will only receive 
a single, standard of care, trigger finger injection on the day they present to the clinic. The next 7 
days, up to two weeks if needed, of follow-up will only be a single short survey question to determine 
pain level. 
All survey data will be collected from the patient in real-time, but the study will include a 
retrospective chart review to collect demographic information, injection specifics, etc.  
Data to be collected: information from your existing medical records, and new information about you 
that is created or collected during this study, such as: history and physical information pertaining to 
trigger finger, nursing and staff notes pertaining to trigger finger, identifiers (name, MRN), 
demographic data (age/date of birth, sex, dominant hand), patient reported outcome measures 
scores, comorbidities (tobacco use, diabetes, fibromyalgia).  
This study does not involve more than minimal risk. Risks from participation in this study include 
typical risks associated with a trigger finger injection: pain at injection site, soreness, etc. 
The subject will receive no direct benefits. Knowledge gained from this study could help change 
standard of care procedures for trigger finger injections to best limit flare reactions afterward. 
 
Target Population & Recruitment Methods  
We will recruit a minimum of 30-40 patients into each treatment group. Power analysis shows that at 
least 30 patients are needed to show a difference of 2-point difference between the two groups 
which corresponds to the minimal clinically important difference on the VAS scale assuming a 
standard deviation of 2.5 points. Accounting for the potential of patient data loss during follow-up 
surveys, we expect to need to consent and enroll 80-100 patients 
Inclusion & Exclusion Criteria –  
Inclusion: Adult, Single trigger injection, First time for the digit to be injected, No prior surgery on digit 
Exclusion: Current oral steroid use, Rheumatoid arthritis, More than one single digit involved, Previous 
injection in same digit, Prior surgery on same digit, Other injections in the same clinic on the same 
day, Under 18, Cognitively impaired individuals, Pregnant women, Prisoners, WVU/WHUH/UHA 
Employees or students 
 
Recruitment –  
Prospective subjects will be identified by the surgeon at the time of their appointment. The surgeon 
will inform the study coordinator of a potential participant, and the study coordinator will approach 
the patient for consent. 
There will be n flyers or other advertisements.  
 
Risk & Benefit 
Risk – Risks from participation in this study include typical risks associated with a trigger finger 
injection: pain at injection site, soreness, etc. 
 
Benefit – The subject will receive no direct benefits. Knowledge gained from this study could help 
change standard of care procedures for trigger finger injections to best limit flare reactions afterward. 

         Investigator Initiated Protocol 
Investigator Resources 
 
 
WVU+kc Protocol #: 2103263450 
PI: Shafic Sraj 
 
Statistical Analysis Plan 
Power analysis showed that a minimum of 30 patients are needed to show a difference of 2-point 
difference between the two groups which corresponds to the minimal clinically important difference 
on the VAS scale assuming a standard deviation of 2.5 points. We will compare the incidence, 
intensity, and time to flare reactions and time to resolution between the two groups using t-test and 
chi square tests as appropriate. 
 
Data Safety Monitoring – Yes, there is a data safety monitoring plan in place for this study. 
 
Safety Monitoring & Unanticipated Event Reporting 
Adverse events will be evaluated regarding their relevance and significance to the study.  
Unanticipated adverse events will be reported to the IRB if the AE is unexpected, serious, and has 
implications for the conduct of the study.  The relationship of the unanticipated, serious adverse 
event to research participation will be determined by the PI.  The PI will report promptly to the IRB 
any adverse events that are unanticipated and involve direct harm to subjects and any unanticipated 
events that involve risk but not direct harm to the subject according the ORIC SOPs.   
An SAE that is study related, unexpected, fatal or life-threatening will be reported to the IRB as soon 
as possible but no later than 5 calendar days of becoming aware of the event.  An SAE that is 
unexpected but not fatal or life-threatening will be reported to the IRB as soon as possible but no 
later than 10 calendar days after first knowledge.  The clinical research coordinator will be monitoring 
and collecting all adverse events. 
 
Study Duration & Timeline 
Enrollment: could take up to a year, depending on how long it takes to recruit enough patients. 
Data Collection: 3-6 months after conclusion of patient enrollment 
Analysis: 3-6 months after conclusion of data collection 
Approximate end date: Two years after IRB approval. 
 
Section III: Informed Consent Process 
 
Protected Health Information (PHI) 
Identify whether your research will deal with protected health information (PHI).  PHI is any 
information in the medical record or designated record set that can be used to identify an individual 
and that was created, used, or disclosed in the course of providing a health care service such as 
diagnosis or treatment. PHI:  This is not limited to only retrospective studies and chart reviews; 
prospective surveys may also be contain questions regarding PHI.  
1. Names 
 
2. All elements of dates (except year) – this includes dates directly related to an individual, 
including birth date, admission date, discharge date, date of death; and all ages over 89 and 
all elements of dates (including year) indicative of such age, except that such ages and 

         Investigator Initiated Protocol 
Investigator Resources 
 
 
WVU+kc Protocol #: 2103263450 
PI: Shafic Sraj 
elements may be aggregated into a single category of age 90 or older 
 
3. Phone number(s) 
 
4. Electronic mail (E-mail) addresses 
 
5. Medical Record numbers   
 
6. Sex 
 
7. Dominant Hand 
 
8. Patient Reported Outcome Measures Scores 
 
9. Comorbidities: Tobacco Use, Diabetes, Fibromyalgia 
 
10. Related to trigger finger: history and physical information, nursing and other staff notes 
 
 
Informed Consent Process 
Prospective subjects will be identified by the surgeon at the time of their appointment. The surgeon 
will inform the study coordinator of a potential participant, and the study coordinator will approach 
the patient for consent. Consent will occur at the WVU Medicine UTC Orthopaedic clinic, in the 
patient's room, at the time of the patient's appointment. Patients will be given a copy of the study 
informed consent form to review before signing, as well as having the study coordinator go over it 
with them. They will be able to ask questions at any time during the process. 
 
 
Confidentiality & Privacy  
Confidentiality –  
The data will be stored in the study REDCap, maintained by the WVCTSI. Identifiers will be stored in a 
separate location from the record ID and only study team members will have access to the 
information. Data will be destroyed 3 years after study closure. All study activity, such as medical 
record reviews, patient phone calls for survey responses, ets will be conducted in a private location 
where incidental viewing could not occur. Any physical copies of patient data collected will be stored 
in a locked desk drawer or fila cabinet at the University Town Center clinic. 
 
 
Section IV: Other Considerations 
 
Conflict of Interest  
No conflicts of interest 
 

         Investigator Initiated Protocol 
Investigator Resources 
 
 
WVU+kc Protocol #: 2103263450 
PI: Shafic Sraj 
Publications, Presentations, & References 
To be determined 
 
References  
 
REFERENCES:  
1.  
Marks MR, Gunther SF. Efficacy of cortisone injection in treatment of trigger fingers and thumbs. 
J Hand Surg Am. 1989 Jul;14(4):722-7. doi: 10.1016/0363-5023(89)90199-8. PMID: 2754207. 
2.  
MCCARTY DJ Jr, HOGAN JM. INFLAMMATORY REACTION AFTER INTRASYNOVIAL INJECTION OF 
MICROCRYSTALLINE ADRENOCORTICOSTEROID ESTERS. Arthritis Rheum. 1964 Aug;7:359-67. doi: 
10.1002/art.1780070402. PMID: 14202574. 
3. Goldfarb CA, Gelberman RH, McKeon K, Chia B, Boyer MI. Extra-articular steroid injection: early 
patient response and the incidence of flare reaction. J Hand Surg Am. 2007 Dec;32(10):1513-20. doi: 
10.1016/j.jhsa.2007.08.002. PMID: 18070637. 
4. Kazuki K, Egi T, Okada M, Takaoka K. Clinical outcome of extrasynovial steroid injection for trigger 
finger. Hand Surg. 2006;11(1-2):1-4. doi: 10.1142/S0218810406003115. PMID: 17080520. 
5. Cecen GS, Gulabi D, Saglam F, Tanju NU, Bekler HI. Corticosteroid injection for trigger finger: blinded 
or ultrasound-guided injection? Arch Orthop Trauma Surg. 2015 Jan;135(1):125-31. doi: 
10.1007/s00402-014-2110-9. Epub 2014 Nov 9. PMID: 25381472.