Determining Optimal Dose of Corticosteroids in COPD Exacerbations: A Pilot Study
Phase: PHASE4
Conditions: COPD
Sponsor: Rutgers, The State University of New Jersey

Determining Optimal Dose of Corticosteroids in COPD Exacerbations: A Pilot Study 
NCT01742338 
March 5, 2018 

Protocol Number: 
PI Name: Jeffrey L Carson, MD 
Protocol Title: Determining Optimal Dose of 
Corticosteroids in COPD Exacerbations: A 
Pilot Study 
1 
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INTERVENTIONAL 
RESEARCH PROTOCOL TEMPLATE 
(HRP-503a) 
 
 
 
STUDY INFORMATION 
 
 
Title of Project: Determining Optimal Dose of Corticosteroids in COPD Exacerbations: A 
Pilot Study 
 
 
Principal Investigator: 
 
Jeffrey L. Carson, MD 
Division of General Internal Medicine 
Department of Medicine 
Rutgers Robert Wood Johnson Medical School 
125 Paterson Street 
New Brunswick, New Jersey 08901 
 
Office: 732-235-7122 
Cell: 908-616-3421 
carson@rwjms.rutgers.edu 
 
 
 
 
PROTOCOL VERSION AND DATE: Version 1 March 5, 2018 

Protocol Number: 
PI Name: Jeffrey L Carson, MD 
Protocol Title: Determining Optimal Dose of 
Corticosteroids in COPD Exacerbations: A 
Pilot Study 
2 
RESERVED FOR IRB STAMP 
DO NOT MODIFY THIS SPACE 
IRB Form Version v120116 
 
 
 
 
 
 
 
 
 
 
 
Table of Contents 
Skip To Section: Hold CTRL + Click (Below) To Follow Link in Blue 
1.0 
Research Introduction 
1.1 
Purpose/Specific Aims 
1.2 
Research Significance 
1.3 
Research Design and Methods 
1.4 
Preliminary Data 
1.5 
Sample Size Justification 
1.6 
Study Variables 
1.7 
Drugs/Devices/Biologics 
1.8 
Primary Specimen Collection 
1.9 
Interviews, Focus Groups, or Surveys 
1.10 
Timetable/Schedule of Events 
2.0 
Project Management 
2.1 
Research Staff and Qualifications 
2.2 
Resources Available 
2.3 
Research Sites 
3.0 
Multi-Site Research Communication & Coordination 
3.1 
Outside Research 
4.0 
Research Data Source/s 
4.1 
Primary Data – Subjects and Specimens 
4.2 
Subject Selection and Enrollment Considerations 
4.3 
Subject Randomization 
4.4 
Secondary Subjects 
4.5 
Number of Subjects 
4.6 
Consent Procedures 
4.7 
Special Consent Populations 
4.8 
Economic Burden and/or Compensation For Subjects 
4.9 
Risks to Subjects 
4.10 
Secondary Data – Record/Chart Reviews, Databases, Tissue Banks, Etc. 
4.11 
Chart/Record Review Selection 
4.12 
Secondary Specimen Collection 
5.0 
Special Considerations 
5.1 
Health Insurance Portability and Accountability Act (HIPAA) 
5.2 
Family Educational Rights and Privacy Act (FERPA) 
5.3 
NJ Access to Medical Research Act 

Protocol Number: 
PI Name: Jeffrey L Carson, MD 
Protocol Title: Determining Optimal Dose of 
Corticosteroids in COPD Exacerbations: A 
Pilot Study 
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5.4 
Code of Federal Regulations Title 45 Part 46 (Vulnerable Populations) 
6.0 
Research Data Protection and Reporting 
6.1 
Data Management and Confidentiality 
6.2 
Data Security 
6.3 
Data Safety And Monitoring 
6.4 
Reporting Results 
7.0 
Data and/or Specimen Banking 
8.0 
Other Approvals/Authorizations 
9.0 
Bibliography 
 
 
 
 
1.1 Purpose/Specific Aims 
 
The goal of the study is to determine whether a high-dose corticosteroid regimen in patients admitted 
to the hospital with COPD exacerbations is associated with better clinical outcomes and at acceptable 
risk of adverse effects compared to a low-dose corticosteroid regimen. The study population includes 
patients ≥ 40 years-old with a ≥ 10 pack-years smoking history and a diagnosis of COPD, emphysema, 
or chronic bronchitis who present to the emergency room with increased dyspnea, increased sputum, 
or increased cough that requires admission to the hospital. We will perform a prospective, 
randomized, double-blinded study to determine if a high-dose corticosteroid regimen, which is 
already in use in clinical practice, decreases treatment failure compared to a low-dose corticosteroid 
regimen that is based on national consensus guidelines. 
 
A. Objectives 
 
Primary Aim: To determine if a high-dose corticosteroid regimen is associated with decreased 
rates of treatment failure compared to a low-dose corticosteroid regimen. 
 
Secondary Aims: 
a) To determine if a high-dose corticosteroid regimen is associated with a reduced length of 
stay. 
b) To determine if a high-dose corticosteroid regimen is associated with better quality of life 
scores. 
 
Tertiary Aim: To determine if a high-dose corticosteroid regimen is associated with an 
increased risk of short-term adverse effects. 
 
B. Hypotheses / Research Question(s) 
1.0 Research Introduction 

Protocol Number: 
PI Name: Jeffrey L Carson, MD 
Protocol Title: Determining Optimal Dose of 
Corticosteroids in COPD Exacerbations: A 
Pilot Study 
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Our hypothesis is that high-dose corticosteroids are associated with a decreased rate of 
treatment failure, shorter length of hospital stay, and improved quality of life with similar risk 
of adverse effects. 
 
1.2 Research Significance 
 
Chronic obstructive pulmonary disease (COPD) is a preventable and treatable disease that is 
characterized by progressive airflow limitation that is not fully reversible. The airflow limitation is 
associated with an abnormal inflammatory response of the lung to noxious particles or gases, such as 
cigarette smoke.1 
Patients with COPD may come into the hospital with frequent acute exacerbations or flares of their 
disease, especially as the severity of their COPD increases.3 These acute exacerbations of COPD 
contribute significantly to morbidity and worsen quality of life.3 In patients with moderate to severe 
COPD, the in-hospital mortality rate was 9.9% with a 1-year mortality rate of 24.4% among those who 
were able to be discharged home.5 
Oral or intravenous corticosteroids are recommended as an addition to other therapies in the 
management of COPD exacerbations.1, 6-9 A 2008 Cochrane review confirms that there is a significant 
reduction in the risk of treatment failure and rate of relapse within a month of treatment with 
corticosteroids. In the steroid treated group, the length of hospital stay was also significantly reduced 
with an increased rate of improvement in lung function and dyspnea.9 The FEV1 measured after 
bronchodilation increased by 90 mL daily up to day 5 of the hospital stay.6 
While corticosteroids are required in the treatment of COPD exacerbations, the dose and duration of 
this treatment is still unclear and remains to be defined. Current consensus guidelines on the dose and 
duration of corticosteroid treatment vary. The Global Initiative for Chronic Obstructive Lung Disease 
(GOLD) recommends 30-40 mg of oral prednisolone daily for 7-10 days.1 The Canadian Thoracic Society 
recommends oral or intravenous 25-50 mg of prednisone equivalent per day for 14 days; however, 
shorter treatment periods of between 7 and 14 days may also be effective.10 In the UK, the National 
Institute for Health and Clinical Excellence (NICE) recommends prednisolone 30 mg orally for 7-14 days; 
although, their consensus guidelines also state, “there is still debate about the optimal dose and 
duration.”11 
Various studies have evaluated the route of administration, dose, and duration of corticosteroid 
treatment in COPD exacerbations. De Jong compared oral to intravenous administration of the same 
dose of prednisolone for 5 days and found no significant difference in treatment failure, length of 
hospital stay, or changes in spirometry and quality of life.12 A large cohort study evaluated different 
doses and found that oral low-dose steroids (prednisone 20-80 mg daily) were associated with a 
decreased risk of treatment failure and length of stay compared to intravenous high-dose therapy (120- 
800 mg prednisone equivalent daily).13 A VA Cooperative study compared placebo to a 2-week and an 8- 
week corticosteroid taper. Rates of treatment failure were significantly higher in the placebo group than 
in the two glucocorticoid groups, but the 8-week regimen was not superior to the 2-week one.7 The 

Protocol Number: 
PI Name: Jeffrey L Carson, MD 
Protocol Title: Determining Optimal Dose of 
Corticosteroids in COPD Exacerbations: A 
Pilot Study 
5 
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effectiveness of shorter corticosteroid regimens has been studied. A 10-day course of steroid treatment 
was more effective than a 3-day course in improving PaO2, FVC and FEV1, and symptom scores for 
dyspnea on exertion.14 Additionally, the REDUCE trial demonstrated non-inferiority of a 5-day regimen of 
prednisone 40mg daily when compared to an extended 14-day course.15 
This research protocol will help further delineate the optimal dose of corticosteroids when given over a 
10-day period consistent with prior research. 
 
 
1.3 Research Design and Methods 
 
We will perform a pilot study evaluating two commonly used doses of corticosteroids in the treatment of 
acute exacerbation of COPD. The study design is a randomized, double-blinded, prospective interventional 
trial. Our research staff will recruit, consent, and enroll patients admitted to the hospital with a diagnosis 
of COPD exacerbation. We will create randomization tables that will be provided to the research 
pharmacist. The research pharmacist will be telephoned, and they will randomly assign the patient to a 
low-dose or high-dose corticosteroid regimen. Medication will be prepared by a research pharmacist to 
maintain blinding. For in-hospital intravenous medication, the research pharmacist will provide to the 
nurses a container with the patient’s name and medication without the dose. For oral medication, the 
pills will be inserted into a capsule and provided to nurses for in-hospital administration. At the time of 
discharge, a container filled with the remaining oral medication will be provided to the patient. Subjects 
receiving intravenous corticosteroid may be discharged to a nursing home before completion of the IV 
component of the regimen. Their regimen will be converted to oral equivalents, and a container will be 
provided to the nursing home. Copies of the patient brochure, signed consent, and written discharge 
instructions will also be provided. All data will be collected by our research staff via chart review of index 
and subsequent hospitalizations within the 30-day follow up period, as well as a phone interview with the 
patient at 30-days. The Clinical COPD Questionnaire will be administered during the phone interview. A 
patient is considered lost to follow-up if the data collection is not collected within 14 days after the 30- 
day follow-up date. In the event that we are unable to contact the patient, we will telephone the 
participant’s personal medical doctor to confirm the patient’s status. If necessary, we will obtain medical 
records for any outpatient physician visits made during the 30-day follow up period. 
 
i. 
Primary Outcome: The composite of treatment failure defined as death, intubation, re-admission 
for COPD exacerbation, or intensification of therapy (increased steroid use, change of antibiotic 
therapy) within a 30-day follow-up period. 
 
ii. 
Secondary Outcomes: Length of hospital stay and quality of life measured by Clinical COPD 
Questionnaire. The CCQ consists of 10 questions about the severity of COPD symptoms and 
limitation of activities over the prior week. 
 
iii. 
Tertiary Outcome: Composite outcome of short-term adverse effects. Defined as hyperglycemia, 
hypertension, adrenal suppression, psychiatric disturbance, infection, and gastrointestinal bleed 
that require a consultation, an invasive procedure, or initiation of a specific therapy. 

Protocol Number: 
PI Name: Jeffrey L Carson, MD 
Protocol Title: Determining Optimal Dose of 
Corticosteroids in COPD Exacerbations: A 
Pilot Study 
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Subject participation in the study ends after the 30 day follow up period. Study staff will also maintain 
contact with the patient’s hospital physician and actively review the patient’s chart during the index 
hospitalization for safety and adverse effect monitoring. Please see the study data collection form for 
additional specific data points that will be collected. 
 
1.4 Preliminary Data 
 
No relevant preliminary data exists in our study. Interim analysis will not be performed on the data 
because of the relatively small sample size of this pilot study. 
 
1.5 Sample Size Justification 
 
This is a pilot study of 125 subjects to determine the rates of the outcomes so an adequate sample size 
can be determined and feasibility established. We do not anticipate including enough patients to have 
adequate power to definitively answer the hypothesis. 
 
1.6 Study Variables 
 
A. Independent Variables, Interventions, or Predictor Variables 
 
Our independent variable is the corticosteroid intervention. We chose to compare two 
commonly used corticosteroid regimens for COPD exacerbation that vary by dosage strength but 
not duration. Both of these regimens may be considered “standard of care.” 
 
B. Dependent Variables or Outcome Measures 
 
i. 
Primary Outcome: The composite of treatment failure defined as death, intubation, re- 
admission for COPD exacerbation, or intensification of therapy (increased steroid use, 
change of antibiotic therapy) within a 30-day follow-up period. 
ii. 
Secondary Outcomes: Length of hospital stay and quality of life measured by Clinical 
COPD Questionnaire. The CCQ consists of 10 questions about the severity of COPD 
symptoms and limitation of activities over the prior week. 
iii. 
Tertiary Outcome: Composite outcome of short-term adverse effects. Defined as 
hyperglycemia, hypertension, adrenal suppression, psychiatric disturbance, infection, and 
gastrointestinal bleed that require a consultation, an invasive procedure, or initiation of a 
specific therapy. 
 
1.7 Drugs/Devices/Biologics 
 
We chose to compare two commonly used corticosteroid regimens for COPD exacerbations, both of 
which might be considered “standard of care.” All corticosteroids will be prepared, stored, and 
dispensed at the RWJUH main pharmacy by the staff research pharmacist. 

Protocol Number: 
PI Name: Jeffrey L Carson, MD 
Protocol Title: Determining Optimal Dose of 
Corticosteroids in COPD Exacerbations: A 
Pilot Study 
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i. 
Low dose arm: Methylprednisolone 10 mg IV q8hrs for 3 days*, then prednisone 40 mg PO daily 
for 4 days, then prednisone 30 mg daily for 1 day, then prednisone 20 mg daily for 1 day, then 
prednisone 10 mg daily x 1 day, then stop. 
 
* If the patient is unable to receive IV medications, every three consecutive doses of 
methylprednisolone will be replaced with a single dose of prednisone 40 mg PO given daily. 
ii. 
High dose arm: Methylprednisolone 40 mg IV q8hrs for 3 days*, then prednisone 80 mg PO daily 
for 4 days, then prednisone 60 mg daily for 1 day, then prednisone 40 mg daily for 1 day, then 
prednisone 20 mg daily for 1 day, then stop. 
 
* If the patient is unable to receive IV medications, every three consecutive doses of 
methylprednisolone will be replaced with a single dose of prednisone 80 mg PO given daily. 
 
If patients in either group are discharged prior to day 4, IV methylprednisolone will be converted 
to PO as above. 
 
1.8 Primary Specimen Collection 
N/A 
 
1.9 Interviews, Focus Groups, or Surveys 
 
A. Administration 
 
The Clinical COPD Questionnaire (CCQ) will be administered by research staff during a telephone 
interview at 30 days following subject enrollment into the study. The patient will be provided 
this document in advance, at the time of hospital discharge, for reference. 
 
B. Study Instruments 
The CCQ is a validated tool utilized in prior literature to assess quality of life in patients with 
COPD. Higher scores indicate increased severity of symptoms and/or poorer quality of life, and 
are associated with increased mortality. 17, 18, 19, 20, 21 
 
In addition to the CCQ, research staff will query the patient about study endpoints during the 
follow-up telephone interview (re-admission, changes to steroid regimen, antibiotic therapy, 
and steroid-associated adverse effects that require a consultation, an invasive procedure, or 
initiation of a specific therapy). 
 
1.10 Timetable/Schedule of Events 
 
Patients will be enrolled and followed for a total of 30 days. If follow-up is still unable to be obtained 14 
days after the 30-day follow-up date, the patient will be considered lost to follow-up. The global 
timetable for the study is unknown, as the volume of patient recruitment is unclear. 

Protocol Number: 
PI Name: Jeffrey L Carson, MD 
Protocol Title: Determining Optimal Dose of 
Corticosteroids in COPD Exacerbations: A 
Pilot Study 
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2.0 Project Management 
 
 
2.1 Research Staff and Qualifications 
 
Jeffrey L Carson, MD, the study Principal Investigator, is the Provost-New Brunswick, Rutgers Biomedical 
Health Sciences, Professor of Medicine Rutgers, Robert Wood Johnson Medical School. Dr Carson has 
extensive experience in leading and conducting randomized clinical trials including the NIH funded 
Transfusion Trigger Trial for Functional Outcomes in Cardiovascular Patients Undergoing Surgical Hip 
Fracture Repair (FOCUS) trial, which enrolled patients from 47 centers from the United States and 
Canada. He is currently the Study Chairman and Principal Investigator of the NIH funded Myocardial 
Ischemia and Transfusion (MINT) trial, which will enroll 3500 patients from over 50 centers in the United 
States and Canada. 
 
James Prister, MD is the Associate Program Director of the Internal Medicine Residency Program Rutgers 
Robert Wood Johnson Medical School and an attending physician Robert Wood Johnson University 
Hospital. Dr Prister is the study co-Investigator who is directly responsible for the ongoing conduct of 
the study. 
 
Helaine Noveck, MPH is a research teaching specialist in the Division of General Internal Medicine, 
Department of Medicine, Rutgers Robert Wood Johnson Medical School. Ms Noveck was the Deputy 
Director of the Clinical Coordinating Center for FOCUS and currently serves in that role for MINT. She is 
experienced in both data management and analysis, having worked on Dr Carson’s research projects for 
the past 24 years. Ms Noveck will serve as the data analyst. 
 
 
2.2 Resources Available 
 
The study will utilize locked file cabinets and a password protected workstation in the GIM office, CAB 
suite 2300. Ms Noveck will keep the key for the file cabinet. 
All research co-investigators undergo initial two-hour training sessions regarding study protocol, 
procedures, and duties. On-going research procedures are supervised by James Prister and the data 
analyst to ensure protocol compliance. 
2.3 Research Sites 
 
Robert Wood Johnson University Hospital 
 
3.0 Multi-Site Research Communication & Coordination 
 
 
N/A 
 
3.1 Outside Research 
 
N/A 

Protocol Number: 
PI Name: Jeffrey L Carson, MD 
Protocol Title: Determining Optimal Dose of 
Corticosteroids in COPD Exacerbations: A 
Pilot Study 
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4.0 Research Data Source/s 
 
 
4.1 Primary Data-Subjects and Specimens 
 
Thirty day follow is obtained from patient/proxy via telephone contact (see data collection form). 
 
4.2 Subject Selection and Enrollment Considerations 
A. Recruitment Details 
Emergency room and medical staff will be informed about the study objectives, eligibility 
criteria, and protocol requirements prior to the initiation of the study. We will only recruit 
patients of physicians who are willing to follow the study protocol. Study staff will be notified of 
potential subjects that are identified by the emergency room staff and physicians. Study staff 
can also access a list of patients in the hospital who are being treated with prednisone or 
methylprednisolone to identify additional potential study subjects. Study staff will assess the 
medical records of each of the potential study subjects and, if they meet all eligibility criteria, 
approach the patient for consent. Eligible patients would have a diagnosis of COPD, 
emphysema, or chronic bronchitis with a presentation of increased dyspnea, increased sputum, 
or increased cough. 
 
B. Source of Subjects 
 
Subjects will be recruited from the RWJUH emergency room and general medical ward. 
 
C. Method to Identify Potential Subjects 
See section A above. 
 
D. Subject Screening 
Individuals will be screened for study inclusion by study staff using the eligibility and screening 
form. 
▪ Inclusion Criteria 
o Patients with a diagnosis of COPD, emphysema, or chronic bronchitis 
o Age ≥ 40 years-old 
o Smoking history ≥ 10 pack-years 
o Presentation to the emergency room with increased dyspnea, increased 
sputum, or increased cough 
o Admission to the hospital 
▪ Exclusion Criteria 
o Alternative diagnosis for cause of dyspnea, increased sputum or cough 
o Patients who require intubation at time of recruitment 
o Patients who are unable to give consent 
o Patients who are pregnant or could be pregnant or are currently breast- 
feeding 

Protocol Number: 
PI Name: Jeffrey L Carson, MD 
Protocol Title: Determining Optimal Dose of 
Corticosteroids in COPD Exacerbations: A 
Pilot Study 
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RESERVED FOR IRB STAMP 
DO NOT MODIFY THIS SPACE 
IRB Form Version v120116 
 
 
 
o Women of child-bearing age who cannot use methods of contraception as 
described in the consent, including condoms, female condoms, cervical 
caps, diaphragms, and IUDs. 
o Patients who were previously entered into the trial and are re-admitted to 
the hospital with a new COPD exacerbation. 
 
A younger population is excluded because COPD is primarily an adult disease. 
 
E. Recruitment Materials 
 
Subjects will be given a copy of the informed consent as well as a short patient brochure 
describing the salient points of the study. 
 
F. Lead Site Recruitment Methods 
 
N/A 
 
4.3 Subject Randomization 
 
At the time of recruitment, subjects are assigned a consecutively numbered patient identifier by the 
study staff. This patient identifier is communicated to the research pharmacy. The research pharmacy 
then assigns a separate randomization identifier based on a previously computer generated 
randomization chart. The randomization identifier is communicated back to the study staff. This 
randomization identifier is associated with a specific treatment arm (low-dose or high-dose) on the 
randomization chart. The treatment arm associated with the randomization identifier is not 
communicated to the research staff because this is a double-blinded study. Study drug is prepared by 
the research pharmacy based on the assigned treatment arm. 
 
4.4 Secondary Subjects 
 
N/A 
 
4.5 Number of Subjects 
A. Total Number of Subjects: 125 
B. Total Number of Subjects If Multicenter Study: N/A 
C. Require Number of Subjects to Complete Research: This is a pilot study and our goal is to 
recruit as close to 125 subjects as possible. 
D. Feasibility Of Recruiting: COPD exacerbation is a common reason for inpatient admission, 
however recruiting may be limited to unquantifiable external factors (ie. patient interest, 
physician participation, etc.). 
 
4.6 Consent Procedures 
A. Consent 
▪ Documenting Consent 

Protocol Number: 
PI Name: Jeffrey L Carson, MD 
Protocol Title: Determining Optimal Dose of 
Corticosteroids in COPD Exacerbations: A 
Pilot Study 
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Informed consent will be obtained directly from the participant using study informed 
consent. If the patient agrees to participate in the trial, the signed IRB approved 
consent form will be placed in the subject’s study file and the recruiter will keep make a 
copy to be placed in the patient’s medical record and a copy to provide to the 
participant. 
 
▪ Waiver of Documentation Of Consent 
 
N/A, all consent will be documented. 
 
▪ Waiver or Alteration of Consent Process 
 
N/A 
 
B. Consent Process 
▪ Location of Consent Process 
 
Consent will take place in the patient’s hospital room. 
 
▪ Ongoing Consent 
The patient will be spoken with daily by the study staff while hospitalized to address any 
patient concerns regarding ongoing consent and potential adverse effects. 
 
▪ Individual Roles for Researchers Involved in Consent 
 
1. Consent Discussion Duration 
The consent discussion is expected to take an average of 15-30 minutes 
depending on the level of subject understanding. 
2. Coercion or Undue Influence 
Vulnerable subjects that are unable to give consent or do not adequately 
understand the study are excluded from recruitment. Aside from paid-for trial 
medication, the study does not incentivize subject participation in any way, 
minimizing undue influence on indigent populations. 
3. Subject Understanding 
After the study is explained to the subjects, study staff will administer the 
Evaluation to Sign Consent which will document the subject’s understanding of 
the study protocol. Only who provide acceptable responses to the Evaluation to 
Sign Consent will be enrolled. 
 
4.7 Special Consent/Populations 
A. Minors-Subjects Who Are Not Yet Adults 
▪ Criteria for Consent of Minors 
N/A 
▪ Wards of the State 

Protocol Number: 
PI Name: Jeffrey L Carson, MD 
Protocol Title: Determining Optimal Dose of 
Corticosteroids in COPD Exacerbations: A 
Pilot Study 
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N/A  
1. Research in NJ Involving Minors 
N/A 
2. Research Outside of NJ Involving Minors 
N/A 
▪ Parental Permission 
N/A 
▪ Non-Parental Permission 
N/A 
▪ Assent Process 
N/A 
1. Documentation of Assent 
N/A 
▪ 
Non-English Speaking Subjects 
 
Non-English speakers will not be recruited 
 
1. Process for Non-English Speaking Subjects 
N/A 
▪ 
Short Form Consent for Non-English Speakers 
No one will be enrolled using the short form consent 
 
B. Adults Unable to Consent / Cognitively Impaired Adults (for interventional studies) 
▪ 
NJ Law-Assessment of Regaining the Capacity To Consent 
N/A, subjects unable to give consent are excluded from this study. 
▪ 
Capacity To Consent 
N/A 
▪ 
NJ Law-Selecting A Witness 
N/A 
▪ 
Removing a Subject 
N/A 
 
4.8 Economic Burden and/or Compensation for Subjects 
A. Expenses 
Subjects will not incur any additional expenses as a result of study participation. 
B. Compensation/Incentives 
Subjects will not be incentivized in any way for participation in the study, with the exception that 
trial medication will be provided at no cost to the subjects. 
 
4.9 Risks to Subjects 
A. Description of Subject Risk 
Patients entered into this study would have received corticosteroids regardless of study 
participation. The optimal dose of corticosteroids in the treatment of COPD exacerbations in 
patients admitted to the hospital is unknown. The proposed regimen for the low-dose 

Protocol Number: 
PI Name: Jeffrey L Carson, MD 
Protocol Title: Determining Optimal Dose of 
Corticosteroids in COPD Exacerbations: A 
Pilot Study 
13 
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IRB Form Version v120116 
 
 
 
corticosteroid group is based on national consensus guidelines, and the regimen for the high- 
dose group, on current clinical practices. Thus, the risks to subjects from study participation are 
comparable to current standard of care. Any patient who does not clinically improve 
appropriately can have their regimen intensified based on the clinical judgement of his/her 
physician. Additionally, if the treating physician feels that the patient is experiencing undue 
adverse effects from study corticosteroid, the patient may be withdrawn from the study at any 
time. Minor side effects (ie. hyperglycemia) from short-term systemic corticosteroids are 
common and generally limited in duration to the duration of treatment. They are an accepted 
consequence of the standard of care for COPD exacerbation. Major adverse effects are 
uncommon. 
B. Procedures for Risks to Embryo, Fetus, and/or Pregnant Subjects 
N/A, these subjects are excluded from the study. 
 
C. Risks to Non-Subjects 
N/A 
 
D. Assessment of Social Behavior Considerations 
Temporary psychiatric symptoms or exacerbation of pre-existing psychiatric disease are 
uncommon but potential side effects of corticosteroid therapy. The duration of these side 
effects are limited to the duration of corticosteroid therapy. Patients entered into this study 
would have received corticosteroids regardless of study participation. Thus, study 
participation is unlikely to increase risk of these side effects. 
▪ Reasonably Foreseeable Risks 
There are no other reasonably foreseeable social behavior risks of participation in this 
study. 
▪ Risk Of Imposing An Intervention On Subject With Existing Condition 
See above. 
▪ Other Foreseeable Risks 
N/A 
▪ Observation And Sensitive Information 
N/A 
E. Minimizing Risks 
Strict measures are in place to ensure patient confidentiality. Direct patient identifiers (names, 
addresses, and telephone numbers) will be collected on a separate form from the clinical data 
and will be kept in a locked file cabinet in the Department of General Internal Medicine, CAB 
suite 2300. The identifiers will never be entered into an electronic database. Subjects will be 
given a sequential study identification number that will be used on all forms that collect clinical 
data and in the electronic database. 
 
 
The treatment regimens being compared are commonly used in current clinical care and would 
have been prescribed for the patients regardless of study participation. If the patient’s 

Protocol Number: 
PI Name: Jeffrey L Carson, MD 
Protocol Title: Determining Optimal Dose of 
Corticosteroids in COPD Exacerbations: A 
Pilot Study 
14 
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IRB Form Version v120116 
 
 
 
symptoms are not adequately relieved by the study medication, the treating physician is 
permitted to administer supplemental steroid as needed. 
 
 
Patients will be followed while in the hospital (for up to 30 days) and at 30 days following study 
entry. All serious adverse events that have occurred will be identified and reported to the 
Institutional Review Board. 
 
 
Any subject deaths will be reported within 24 hours of identification. Serious events will be 
defined as any event that is life threatening requires or prolongs hospitalization, produces a 
disability, results in a congenital anomaly/birth defect, or other conditions which in the 
judgment of the investigators represent significant hazards. All serious adverse events will be 
reported within one week of identification. All unexpected events meeting will be reported 
within two weeks of identification if they meet the following criteria: 
 
 
Unexpected: not identified in nature, severity or frequency in the current IRB-approved 
research protocol, the informed consent document, the package insert for a given drug 
or the investigator’s brochure. 
Associated with the study intervention: there is a reasonable possibility that the event 
may have been caused by the research intervention. 
F. Certificate of Confidentiality 
N/A 
G. Potential Benefits to Subjects 
There is no direct benefit to study participants. 
H. Provisions to Protect the Privacy Interests of Subjects 
Subjects will interact with a limited number of study staff, primarily during the initial 
recruitment/inpatient follow-up period. Any privacy interests will be honored by study staff. 
 
I. Research Team Access To Subject Data 
Study participants will be asked to sign a Release of Medical Record form, allowing the research 
team to access medical information from all subsequent hospitalizations and outpatient 
physician visits within the 30-day follow up period. 
 
4.10 Secondary Data – Records/Chart Reviews/Databases/Tissue Banks/etc. 
 
4.11 Chart/Record Review Selection 
For the index hospitalization, study staff will review the hospital medical record (paper and electronic) at 
the time of discharge for each outcome. The electronic record system is Sunrise Clinical Manager. Paper 
data collection forms that contain personal identifiers and health information will be kept locked in a 

Protocol Number: 
PI Name: Jeffrey L Carson, MD 
Protocol Title: Determining Optimal Dose of 
Corticosteroids in COPD Exacerbations: A 
Pilot Study 
15 
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filing cabinet in the Department of General Internal Medicine, CAB suite 2300. Study variables and 
outcomes will be entered into an electronic database using identification numbers for the study 
subjects. With the exception of dates, the database will not contain personal identifiers. Only study staff 
will have access to the paper data collection forms and electronic database. In addition, all electronic 
data will be password-protected and stored on a HIPAA compliant university computer in the 
Department of General Internal Medicine. Please see the Data Collection Form for variables that will be 
collected/analyzed. Any forms linking collected data with patient identifiers will be destroyed at the 
completion of the study (2 years following termination of patient enrollment). 
 
4.12 Secondary Specimen Collection 
 
N/A 
 
5.0 Special Considerations 
 
 
5.1 Health Insurance Portability and Accountability Act (HIPAA) 
HIPAA data (patient identifiers) will be collected as part of the data collection process. This data will not 
be disclosed and all patient identifiers will be destroyed at the completion of the study following data 
analysis. Authorization for study staff to obtain/analyze HIPAA data is included in the consent form. 
 
5.2 Family Educational Rights and Privacy Act (FERPA) 
N/A 
 
 
5.3 NJ Access to Medical Research Act 
N/A 
 
5.4 Code of Federal Regulations Title 45 Part 46 (Vulnerable Populations) 
A. “Special" Classes Of Subjects 
(1) Pregnant Women: N/A, these subjects are excluded from the study. 
(2) Neonates: N/A, these subjects are excluded from the study. 
(3) Neonates of Uncertain Viability: N/A, these subjects are excluded from the study. 
(4) Prisoners: N/A, these subjects are excluded from the study. 
(5) Children: N/A, these subjects are excluded from the study. 
(6) Cognitively Impaired Adults: N/A, these subjects are excluded from the study. 
 
6.0 Research Data Protection and Reporting 
 
 
6.1 Data Management and Confidentiality 
A. Descriptive statistics (e.g., means, standard deviations, ranges, frequency distributions) will 
be examined for all relevant measures, and transformations of measures will be considered on 
the bases of distribution diagnostics and outlier analysis. The baseline characteristics of the 
patients in each of the two arms of the trial will be described and compared using chi-square 
statistics for categorical variables and t-tests or Wilcoxon statistics for continuous variables. 

Protocol Number: 
PI Name: Jeffrey L Carson, MD 
Protocol Title: Determining Optimal Dose of 
Corticosteroids in COPD Exacerbations: A 
Pilot Study 
16 
RESERVED FOR IRB STAMP 
DO NOT MODIFY THIS SPACE 
IRB Form Version v120116 
 
 
 
 
The intention-to-treat principle will be used for all randomized comparisons of study outcomes. 
The event rates for the primary, secondary, and tertiary clinical outcomes will be compared 
according to assigned corticosteroid group using chi-square statistics. The test for differences 
between groups in the composite primary outcome will be conducted at an alpha level of 0.05. 
The event rates for the individual clinical events and the additional pre-specified clinical events 
will be tested by treatment group with an alpha=0.01 to adjust for multiple comparisons. Event 
rates, absolute differences, and relative risks will be estimated, and 95% confidence intervals 
will be calculated. 
B. This is a pilot study to establish an adequate sample size for a larger scale study as well as 
baseline event rates, thus a power analysis is not included in this submission. 
C. Paper data will be stored in a locked filing cabinet in the Department of General Internal 
Medicine. A password-protected electronic database (that does not contain patient identifiers) 
will be stored on a HIPAA-compliant university computer at the same location. Helaine Noveck 
will have sole access to this data until the study enters the data analysis phase. All study 
personnel are already trained in HIPAA procedures and have signed HIPAA confidentiality 
agreements as part of obtaining access to the Sunrise Clinical Manager system. 
 
D. Collected data will be reviewed for quality and internal consistency by study staff after initial 
collection and before the data analysis phase of the study. 
 
E. Data to be collected includes patient identifiers and can be found in the data collection form. 
This data will be stored on paper and in an electronic database as detailed above. Paper data 
will be transported by research staff involved in patient recruitment/data collection to the 
central data repository at the General Internal Medicine office. Patient identifying data will be 
stored for 2 years following termination of patient enrollment (completion of the study), at 
which point all patient identifiers will be permanently destroyed. De-identified data will be 
retained indefinitely for future research purposes. All co-investigators will potentially have 
access to research data for data analysis/quality control purposes. Access to the data is 
controlled by the study data analyst, who maintains the central repository of paper/electronic 
data. 
 
6.2 Data Security 
Paper data collection forms that contain personal identifiers and health information will be kept locked 
in a filing cabinet in the Department of General Internal Medicine. Study variables and outcomes will be 
entered into an electronic database using identification numbers for the study subjects. With the 
exception of dates, the database will not contain personal identifiers. Only study staff will have access to 
the paper data collection forms and electronic database. In addition, all electronic data will be 
password-protected and stored on a HIPAA compliant university computer in the Department of 
General Internal Medicine. Any forms linking collected data with patient identifiers will be destroyed at 
the completion of the study (2 years following termination of patient enrollment). 
 
6.3 Data and Safety Monitoring 
A. Periodic Data Evaluation 

Protocol Number: 
PI Name: Jeffrey L Carson, MD 
Protocol Title: Determining Optimal Dose of 
Corticosteroids in COPD Exacerbations: A 
Pilot Study 
17 
RESERVED FOR IRB STAMP 
DO NOT MODIFY THIS SPACE 
IRB Form Version v120116 
 
 
 
Study staff responsible for data collection will review that data for potential corticosteroid 
adverse effects / unexpected patient outcomes and report problems to Helaine Noveck, James 
Prister, and Jeff Carson. Study policies involving adverse effect / death reporting to the IRB are 
in place and detailed above. 
B. Type of Data Evaluated 
Data reviewed includes predefined corticosteroid adverse effects in the data collection form and 
unexpected patient outcomes discovered by study staff. 
C. Collection of Safety Information 
Safety information is collected by study staff interviewing the patient and reviewing their chart 
while hospitalized, as well as phone interview and final chart review of index hospitalization and 
subsequent healthcare encounters at 30-day follow up. 
D. Frequency Of Data Collection 
Safety information is collected daily while the subject is hospitalized, starting at the point of 
patient recruitment. It is collected once more at the 30-day subject follow up. 
E. Reviewer of Data 
Study staff (co-investigators) responsible for patient recruitment/data collection/patient follow 
up will conduct an initial review of the data. Potential problems are reported to Helaine Noveck, 
James Prister, and Jeff Carson who will provide secondary review. 
F. Schedule Of Review Of Cumulative Data 
Cumulative data is not reviewed in this study, as it is a pilot study with a small sample size and is 
not powered to attain statistical significance for secondary safety outcomes. 
G. Tests for Safety Data 
N/A, see section F above. 
H. Suspension of Research 
Research will be immediately suspended if a serious, unexpected adverse effect is reported that 
is reasonably thought to be a direct result of the study drug and is thought to pose a risk to 
other study subjects beyond that of receiving standard-of-care doses of corticosteroids. 
 
6.4 Reporting Results 
A. Sharing of Results with Subjects 
Results will not be shared with study subjects since no data is collected that is not ordered by 
the patient’s treating physician. 
B. Individual Results 
N/A, see section A above. 
C. Aggregate Results 
Aggregate results will not be available for an extended period of time following study 
completion and will not be shared on an individual basis with study subjects. The study results 
will be published in a scientific journal for public consumption. 
D. Professional Reporting 
The study results will be published in a scientific journal for public consumption. 
E. ClinicalTrials.Gov Registration And Data Reporting 
The study is registered on ClinicalTrials.gov. 
 
7.0 Data and/or Specimen Banking 
 

Protocol Number: 
PI Name: Jeffrey L Carson, MD 
Protocol Title: Determining Optimal Dose of 
Corticosteroids in COPD Exacerbations: A 
Pilot Study 
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N/A 
 
8.0 Other Approvals/Authorizations 
 
N/A 
 
9.0 Bibliography 
 
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obstructive pulmonary disease: GOLD executive summary.” Am J Respir Crit Care Med. 176.6 
(2007): 532-55. 
2. “Chronic obstructive pulmonary disease, data fact sheet.” U.S. Department of Health and 
Human Services, National Institutes of Health, National Heart, Lung, and Blood Institute. NIH 
Publication No. 03-5229. March 2003. Web. 20 Nov. 2011. < 
http://www.uptakemedical.com/pdfs/copd_fact.pdf>. 
3. Hurst JR, et al. “Susceptibility to exacerbation in chronic obstructive pulmonary disease.” N Engl 
J Med. 363.12 (2010): 1128-38. 
4. Seemungal TA, Hurst JR, Wedzicha JA. “Exacerbation rate, health status and mortality in COPD – 
a review of potential interventions.” Int J Chron Obstruct Pulmon Dis. 4 (2009): 203-23. 
5. Wang, Q, and J Bourbeau. “Outcomes and health-related quality of life following hospitalizations 
for an acute exacerbation of COPD.” Respirology. 10.3 (2005): 334-40. 
6. Davies L, Angus RM, Calverley PM. “Oral corticosteroids in patients admitted to hospital with 
exacerbations of chronic obstructive pulmonary disease: a prospective randomised controlled 
trial.” Lancet. 354 (1999): 456-60. 
7. Niewoehner DE, et al. “Effect of systemic glucocorticoids on exacerbations of chronic 
obstructive pulmonary disease. Department of Veterans Affairs Cooperative Study Group.” N 
Engl J Med. 340 (1999): 1941-7. 
8. Aaron SD, et al. “Outpatient oral prednisone after emergency treatment of chronic obstructive 
pulmonary disease.” N Engl J Med. 348.26 (2003): 2618-25. 
9. Walters JA, et al. “Systemic corticosteroids for acute exacerbations of chronic obstructive 
pulmonary disease.” Cochrane Database Syst Rev. 1 (2009): CD001288. 
10. Tunks M, and D Miller. “Canadian Thoracic Society recommendations for management of 
chronic obstructive pulmonary disease – 2008 update – highlights for primary care.” Can Respir 
J. 15.4 (2008): 219. 
11. National Clinical Guideline Centre. (2010) Chronic obstructive pulmonary disease: management 
of chronic obstructive pulmonary disease in adults in primary and secondary care. London: 
National Clinical Guideline Centre. Available from: 
http://guidance.nice.org.uk/CG101/Guidance/pdf/English. 
12. De Jong YP, et al. “Oral or IV prednisolone in the treatment of COPD exacerbations: a 
randomized, controlled, double-blind study.” Chest. 132.6 (2007): 1741-7. 
13. Lindenauer PK, et al. “Association of corticosteroid dose and route of administration with risk of 
treatment failure in acute exacerbation of chronic obstructive pulmonary disease.” JAMA. 
303.23 (2010): 2359-67. 
14. Sayiner A, et al. “Systemic glucocorticoids in severe exacerbations of COPD.” Chest. 119.3 
(2001): 726-30. 

Protocol Number: 
PI Name: Jeffrey L Carson, MD 
Protocol Title: Determining Optimal Dose of 
Corticosteroids in COPD Exacerbations: A 
Pilot Study 
19 
RESERVED FOR IRB STAMP 
DO NOT MODIFY THIS SPACE 
IRB Form Version v120116 
 
 
 
15. Schuetz P, et al. “Short versus conventional term glucocorticoid therapy in acute exacerbation of 
chronic obstructive pulmonary disease – the “REDUCE” trial.” Swiss Med Wkly. 140 (2010): 
w13109. 
16. National Asthma Education and Prevention Program Expert Panel. “National Asthma Education 
and Prevention Program Expert Panel Report II: guidelines for the diagnosis and management of 
asthma.” NIH Publication 97-4051. Bethesda, MD: National Institutes of Health; 1997. 
17. van der Molen T, et al. “Development, validity and responsiveness of the Clinical COPD 
Questionnaire.” Health Qual Life Outcomes. 2003 Apr 28;1:13. 
18. Reda AA, et al. “Reliability and validity of the clinical COPD questionniare and chronic respiratory 
questionnaire.” Respir Med. 2010 Nov;104(11):1675-82. Epub 2010 Jun 11. 
19. Kocks JW, et al. “Health status measurement in COPD: the minimal clinically important 
difference of the clinical COPD questionnaire.” Respir Res. 2006 Apr 7;7:62. 
20. Kocks JW, et al. “Health status in routine clinical practice: validity of the clinical COPD 
questionnaire at the individual patient level.” Health Qual Life Outcomes. 2010 Nov 16;8:135. 
21. Josefin Sundh, et al. “Clinical COPD Questionnaire score (CCQ) and mortality.” Int J Chron 
Obstruct Pulmon Dis. 2012; 7: 833–842.