Clinical trial NCT04402970
Conditions: SARS-CoV 2 ARDS
Sponsor: University of Missouri-Columbia
Start date: 2020-06-19; Completion date: 2020-12-31
Enrollment: 30 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This study is designed to evaluate a potential mechanism by which a hyperactive immune response may contribute to death from SARS-CoV-2; by an excessive neutrophil-mediated deposition of cell-free DNA in neutrophil extracellular traps (NET). Excessive amounts of NETs can increase rigidity of mucus, clog airways, and be agents for the development of acute respiratory distress (Narasaraju et al., Am J Pathol. 2011). Many aspects of this pathway have been observed in severe SARS-CoV-2 (Zhang et al., Respiratory research. 2020). Dornase alfa (DNAse I; Pulmozyme (Genentech) is a nebulized drug that works by degrading cell-free DNA and thus promoting airway clearance and recovery. The investigators hypothesize that by thinning mucus and degrading these NETs further lung damage may be prevented and a reduction in time to recovery may occur. The two aims of the study are to see if inhaled/nebulized dornase alfa will improve clinical outcome measures in SARS-CoV-2 related acute respiratory distress syndrome (ARDS) and to see if dornase alfa reduces the amount of bronchoalveolar lavage and blood markers of NET activity.

The study will recruit patients who are on mechanical ventilation for respiratory failure related to SARS-CoV-2 positive infection and have ARDS based upon Berlin criteria.

The investigators aim to recruit 10-20 patients for this study.

Detailed description:
Severe cases of SARS-CoV-2 infection have shown an inflammatory neutrophil and mucus-mediated airway exclusion pathway similar to previously described acute respiratory distress syndrome (ARDS) in other viral syndromes (Narasaraju et al., Am J Pathol. 2011). Lung neutrophilia in ARDS is related to significant neutrophil extracellular trap (NET) production and formation. Thus, NET production is likely contributing to the severe lung pathology in SARS-CoV-2 (Yu Zuo et al. Journal of Clinical Investigation Insight. 2020). Recent connections have been made between NET formation in SARS-CoV-2 patients and excessive thrombosis and the development of cytokine storm further warranting evaluation as a potential site for consideration of treatment (Barnes, Betsy et al. J exp Med. 2020). Dornase alfa (Pulmozyme) is a recombinant human deoxyribonuclease I, that acts as a mucolytic by cleaving extracellular chromosomal DNA from NETs and other cell-free DNA. Unknown are the effects of dornase alfa therapy on SARS-CoV-2 related ARDS and if therapy with dornase alfa truly reduces the amount of NETs in the severely damaged lungs.

This study is a non-randomized, single-center, open-label clinical trial to evaluate the potential benefit and cellular mechanism of nebulized dornase alfa administration in mechanically ventilated patients with SARS-CoV-2 related ARDS. Evaluation of dornase alfa effects at a cellular level will be measured by analysis of blood samples before and after the 3 days of therapy for cell-free DNA, quantification of citrullinated histone H3, quantification of Myeloperoxidase-DNA complexes and analysis of bronchoalveolar lavage samples for quantification of NETs and cell count and differential.

Arms: arm 1: Patient to receive inhaled/nebulized dornase alfa (Pulmozyme) 2.5 mg twice daily in the ventilator circuit for 3 days, along with standard of care for ARDS. arm 2: Standard of care provided for ARDS.
Interventions: intervention 1: Dornase Alfa Inhalation Solution
Intervention descriptions: intervention 1: Nebulized dornase alfa

Protocol documents:
Prot_SAP_002.pdf: 
Study Title: Dornase Alfa for ARDS in Patients 
with SARS-CoV-2 
 
NCT number: 04402970 
 
Document Date: Last approved/updated 
3/08/2021 


Background and Significance 
Health care systems across the world are being inundated with patients who are critically ill due to 
infection with Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) causing 
Coronavirus Disease 2019 (COVID-19). Around 10% of those infected will develop the most severe 
manifestation of the disease requiring admission to an intensive care unit1. Early reports suggested 
neutrophil extracellular traps (NETs) as being a potential contributor to the severity of disease in 
some patients with COVID-192. The primary innate immune role for NETs is to trap and kill invading 
microbes, but in severe cases of COVID-19, NETs appear to cause significant morbidity in the lungs 
with associated microthrombi formation, endothelial damage, capillaritis, neutrophilic mucositis and 
mucus accumulation3-6. Plasma levels of NET activity are increased in patients who requiring 
intubation and are inversely correlated with arterial blood oxygen content to fraction of inspired 
oxygen ratio (PaO2/FiO2)7. Dornase alfa, currently is in use in patients with Cystic Fibrosis, works by 
degrading large extracellular DNA in the airways8,9. We proposed a trial of using inhaled dornase alfa 
as a therapeutic target to reduce excess NETs in patients with acute respiratory distress syndrome 
(ARDS) secondary to COVID-19 pneumonia, with outcome aims including improved lung compliance 
and gas exchange10.  
 
Aims and Objectives 
Aim #1: Determine if use of nebulized dornase alfa in ARDS secondary to COVID-19 will lead to 
improved pulmonary mechanics as measured by surrogate values of PaO2/FiO2 and static lung 
compliance.  
Aim #2: Determine if use of nebulized dornase alfa in ARDS secondary to COVID-19 will lead to a 
reduction in alveolar and serum NET activity. 
 
 
 


 
Research Design 
A single center, non-randomized, controlled before-and-after clinical study was designed to examine 
the effects of inhaled dornase alfa in patients with acute respiratory distress syndrome secondary to 
COVID-19 pneumonia. A second standard of care patient population is to be collected as a case 
control group for comparison. After inclusion to the study and consent has been obtained, we will 
collect blood samples and perform diagnostic flexible bronchoscopy with bronchoalveolar lavage 
(BAL). Patients will then receive nebulized dornase alfa via vibrating mesh nebulizer through the 
ventilator circuit twice daily for 3 days. On day 4 after randomization, blood samples and BAL fluid 
samples will again be collected to determine change in serum and alveolar NET activity. Therapy will 
be discontinued in any patients who develop treatment failure defined as an increase in FiO2 by 20%, 
reduction in static lung compliance by more than 10 or need for rescue therapies such as 
extracorporeal membrane oxygenation (ECMO) or inhaled nitric oxide. Primary outcome measure will 
be change in arterial oxygen saturation to inhaled fraction of oxygen (PaO2/FiO2) before and after 
therapy. Secondary outcomes to be included will be change in static lung compliance, duration of 
mechanical ventilation, length of ICU stay, length of hospitalization, secondary bacterial infections, 
and mortality. 
Study Population and Data Collection 
Patients are to be recruited from the medical intensive care unit at the University of Missouri, a 250-
bed academic tertiary care medical center, after confirmation of ARDS secondary to SARS-CoV-2 
infection and progression of care to requiring mechanical ventilation. Inclusion criteria included age ≥ 
18 years, hospitalized, and mechanically ventilated for illness related to SARS-CoV-2 infection, with 
individual or surrogate ability to sign informed consent, and negative urine-based pregnancy test in 
female patients. Exclusion criteria included contraindication or intolerance to dornase alfa, length of 
mechanical ventilation expected to be less than 48 hours, life expectancy less than 24 hours based 
upon judgment of treatment physician, pregnancy, or inability to obtain informed consent. For the first 


5 days and at day 14 if applicable, daily measurements of PaO2/FiO2, static lung compliance, and 
positive end expiratory pressure (PEEP) will be collected. Demographic and clinical data of the 
patients to be obtained from electronic medical records at enrollment. Clinical study information will 
include age, sex, co-morbidities, therapies received, serological testing, ventilator data, bacterial and 
viral culture data, days of hospitalization, days in the intensive care unit, days of mechanical 
ventilation and mortality.  
 
Primary Statistical Plan and Analysis 
The primary hypothesis for this study is that by giving an inhaled medication targeting alveolar NET 
formation there will be an improvement in alveolar gas exchange. A control group for comparison is 
added who will have received standard of care. Improvement in alveolar gas exchange will be defined 
as a change in PF ratio from baseline for both the treatment and control groups with comparison of 
95% CI between groups. Secondary endpoints of change in static lung compliance and change in 
PEEP will be analyzed in a similar fashion to change in PF ratio. The study is not powered to 
determine additional secondary endpoints such as mortality and length of hospitalization, but values 
will be collected and analyzed as unpaired t-test with significant p-value < 0.05. Bronchoalveolar fluid 
analysis for MPO-DNA will be compared before and after therapy with paired t-test analysis with 
significant p-value < 0.05.  
 
Potential Impact 
 
Resources 
1. Emanuel EJ, Persad G, Upshur R, et al. . Fair allocation of scarce medical resources in the 
time of Covid-19. N Engl J Med. 2020;382(21):2049-2055. 
2. Earhart AP, Holliday ZM, Hofmann HV, Schrum AG. Consideration of dornase alfa for the 
treatment of severe COVID-19 acute respiratory distress syndrome. New Microbes New 
Infect. 2020;35:100689.  


3. Barnes BJ, Adrover JM, Baxter-Stoltzfus A, et al. Targeting potential drivers of COVID-19: 
Neutrophil extracellular traps. J Exp Med. 2020;217(6):e20200652. doi:10.1084/jem.20200652 
4. Schönrich G, Raftery MJ. Neutrophil extracellular traps go viral. Front Immunol. 2016;7:366. 
5. Kambas K, Chrysanthopoulou A, Vassilopoulos D, et al. Tissue factor expression in neutrophil 
extracellular traps and neutrophil derived microparticles in antineutrophil cytoplasmic antibody 
associated vasculitis may promote thromboinflammation and the thrombophilic state 
associated with the disease. Ann Rheum Dis. 2014;73(10):1854-1863. 
doi:10.1136/annrheumdis-2013-203430 
6. Brinkmann V, Reichard U, Goosmann C, et al. Neutrophil extracellular traps kill bacteria. 
Science. 2004;303(5663):1532-1535. doi:10.1126/science.1092385 
7. Middleton EA, He XY, Denorme F, et al. Neutrophil extracellular traps contribute to 
immunothrombosis in COVID-19 acute respiratory distress syndrome. Blood. 2020; 136(10): 
1169-1179. doi:10.1182/blood.2020007008 
8. Shak S, Capon DJ, Hellmiss R, Marsters SA, Baker CL. Recombinant human DNase I 
reduces the viscosity of cystic fibrosis sputum. Proc Natl Acad Sci U S A. 1990;87(23):9188-
9192. doi:10.1073/pnas.87.23.9188 
9. Ramsey BW, Astley SJ, Aitken ML, et al. Efficacy and safety of short-term administration of 
aerosolized recombinant human deoxyribonuclease in patients with cystic fibrosis. Am Rev 
Respir Dis. 1993;148(1):145-151. doi:10.1164/ajrccm/148.1.145 
10. Wang, Q., C. M. Doerschuk, and J. P. Mizgerd.  Neutrophils in innate immunity. Semin Respir  
Crit. Care Med. 2004. 25:33-41. 
 

ICF_004.pdf: 
Study Title: Dornase Alfa for ARDS in Patients 
with SARS-CoV-2 
 
NCT number: 04402970 
 
Document Date: Last approved/updated 
4/30/2020 


 
 
 
 
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CONSENT FORM AND HIPAA AUTHORIZATION FOR PARTICIPATION IN A RESEARCH 
STUDY  
 
INVESTIGATOR’S NAME: ZACH HOLLIDAY  
 
 
PROJECT IRB #:  2022206 
 
STUDY TITLE: INHALED DORNASE ALFA FOR TREATMENT OF ARDS IN PATIENTS 
WITH SARS-COV-2  
 
We invite you to take part in this research study. This consent form tells you why we are doing 
the study, what will happen if you join the study, and other important information about the 
study. 
 
If you are reading this as the person legally authorized to consent on the participant’s behalf, 
“you” refers to the participant. 
 
Please take as much time as you need to read this consent form. You can discuss it with your 
family, friends, or personal doctor. If there is anything you do not understand, please ask us to 
explain. Then you can decide if you want to take part in the study or not.  
 
The Principal Investigator (also called the study doctor) is Zach Holliday, MD. The people 
working with Zach Holliday, MD on this study are called the study team. 
 
WHAT SHOULD I KNOW BEFORE I DECIDE WHETHER TO TAKE PART IN THIS 
STUDY?  
• Research studies help us to learn new things and test new ideas about treating certain 
conditions/diseases.  
• Taking part in a research study is voluntary. You decide if you want to take part, and you 
can stop taking part at any time. Your regular medical care at the University of Missouri 


 
 
 
 
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Hospitals and Clinics will not be affected now or in the future if you decide you do not 
want to be in this study. 
• We are doing this study because there is evidence that using inhaled dornase alfa may 
improve respiratory outcomes in patients with SARS-CoV-2 respiratory failure. We hope 
to learn if this intervention will indeed improve outcomes and if so, by what cellular 
mechanism. 
• We invite you to take part in this study because you have been effected by SARS-CoV-2 
related respiratory failure.  
• About 5-10 people will take part in this study at the University of Missouri. 
• If you take part in this study, you will have blood tests and flexible bronchoscopy with 
sampling. You will also receive dornase alfa as an inhaled medication. We will explain 
these procedures in this form. 
• If you join this study, you will not have to stop your condition treatment for as long as 
you are in the study. 
• The total amount of time you could be in this study is about 3 months.   
• Taking part in this study may or may not make your health better. We hope that the 
information we learn from this study will help in the future treatment of people with 
SARS-CoV-2 related respiratory failure.  There is no guarantee that taking part in this 
research will result in any improvement in your condition. 
• The specimens we take from you for this study may be used to develop new products that 
the sponsor would sell. You will not receive any money from these sales. 
• As with any research study, there are risks that we know about and there may be some we 
don’t know about. We will explain these risks in this form. 
• We will only include you in this study if you give us your permission first by signing this 
consent form. 
 
WHY ARE THE RESEARCHERS DOING THIS STUDY? 
In this study, we want to find out if a drug called dornase alfa (also called the study drug in this 
form), is effective at improving respiratory symptoms in people with SARS-CoV-2.  
 


 
 
 
 
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Dornase alfa is approved by the U.S. Food and Drug Administration (FDA) for use in patients 
with respiratory disease such as cystic fibrosis but is not approved in patients with SARS Co-V 
2. Dornase alfa  may help patients recover more quickly t we won’t know until we do more 
research studies. 
 
We don’t know if this study will help you. Your condition may get better, but it could stay the 
same or even get worse. We hope the information we get from this study will help us to develop 
better treatment for SARS C0-V 2 in the future. 
 
WHAT WILL HAPPEN IF I TAKE PART IN THIS STUDY? 
Screening Tests 
If you decide to join this study, you will sign this form and then you will have some screening 
tests to see if you qualify to be in the study. These are the screening tests: 
• Medical Chart Review: The study doctors will review your medical chart. 
• Blood Tests: We will take about 5 teaspoons of blood from a vein in your arm for some 
tests. 
• Pregnancy Tests: The drug used in this study may affect unborn babies. For this reason, 
pregnant women cannot take part in this study. If you are a female who can become 
pregnant (you have had your first period and have not reached menopause), we will do a 
urine pregnancy test to make sure you are not pregnant. 
 
If the results of these tests show that you can be in the study, you will start in the study the next 
day. If you do not qualify to be in the study, the study doctor will discuss other options with you 
and/or refer you back to your regular doctor. 
 
 
 
 
 
 


 
 
 
 
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Study Tests and Procedures 
If you take part in this study, you will have the following tests and procedures: 
• Prior to starting therapy, you will undergo blood sampling and flexible bronchoscopy 
with bronchoalveolar lavage which will already be a part of your routine care.  
• After baseline samples have been obtained you will receive inhaled dornase alfa 2.5 mg 
twice daily for 3 days (6 doses).  
• After all doses have been completed, follow up blood sampling and flexible 
bronchoscopy with bronchoalveolar lavage will be obtained to determine the effects of 
therapy; these sampling studies may or may not be a part of your routine care. We will 
use excess blood not used in clinical testing at each time point so no additional blood 
sampling will be required. The amount of bronchoalveolar lavage fluid to be collected per 
time point (2 sampling time points) will be 10-20 cc. All procedures and blood draws will 
be performed in the medical intensive care unit in your room. The follow up (72 hours 
after starting therapy) flexible bronchoscopy is an optional procedure. You do not have to 
agree to the 72-hour bronchoalveolar lavage, if performed not as part of your clinic care, 
to take part in this study. At the end of this consent form, we will ask you if we can keep 
your samples and store them for future testing. No further samples will be obtained after 
hospitalization.  
 
Collection of the follow up 72-hour bronchoalveolar lavage are optional to be apart of the study 
and are not required for participation. These samples though will be helpful in determining if the 
drug has a meaningful effect.  
 
We will keep the information and samples we collect from you for this study to use in future 
research/to share with other investigators to use in future studies without asking for your consent 
again. Information that could identify you will be removed from your research data/samples so 
no one will know that it/they belong to you. Agreeing to future use of information and samples is 
optional and is not required to be a part of the study.  
 


 
 
 
 
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Your samples may be used by the investigator to develop new treatments that may be sold 
commercially for profit. You will not share in these profits. 
  
 
 
We will tell you if we learn information from these procedures that may be important for you to 
know. It is possible that this will mean you need more testing or treatment for a new or existing 
medical condition.  You and/or your health plan/insurance will be responsible for the costs of 
this extra testing and/or treatment. 
 
HOW LONG WILL I BE IN THE STUDY? 
You will be in this study for about 90 days.  
You will take the inhaled dornase alfa for at least 3 days. 
After the drug is finished, we want to keep in touch with you to follow your health over time. We 
will call you monthly for 3 months and ask about symptoms. 
 
CAN I STOP BEING IN THE STUDY? 
You can stop being in the study at any time without giving a reason. If you stop being in the 
study, your regular medical care will not change. Leaving the study will not affect your future 
medical care at the University of Missouri.  
 
There is no penalty to you if you do not join the study or if you leave it early. You will not 
lose any benefits you are entitled to if you leave the study. 
 
If you decide to stop participating in the study, you should discuss your decision with the study 
doctor. Early termination will have no effect on your clinical care and will only consist of not 
receiving additional doses of the drug.  
 


 
 
 
 
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The study doctor may decide to take you off this study at any time, even if you want to stay in 
the study. The study doctor will tell you the reason why you need to stop being in the study. 
These reasons may be: 
• If it is in your best medical interest 
• Your condition gets worse 
• The whole study is stopped 
• New information becomes available about the study drug 
 
If necessary, the study doctor will arrange for you to continue your medical care with your 
regular doctor. 
 
WHAT HEALTH RISKS OR PROBLEMS CAN I EXPECT FROM THE STUDY? 
There are risks to taking part in any research study. There is a risk that you may get a drug that 
does not help your condition or makes it worse. There may also be problems (also called side 
effects) we do not know about yet. If we learn about new important risks and side effects, we 
will tell you. We will tell you about any new information we learn that may affect your decision 
to continue taking part in the study. 
 
Dornase alfa can affect people in different ways. Not everyone gets the same side effects. Side 
effects may be mild or very serious. Many go away soon after you stop taking the drug. Some 
side effects can last a long time or never go away. You may receive other drugs to make side 
effects less severe and uncomfortable.  Complications of some of the side effects listed below 
may lead to life-threatening events such as anaphylactic reaction.  
 
We will closely watch everyone in the study for side effects. You need to tell the study doctor 
immediately if you have any problems, side effects, or changes in your health.  Investigator’s 
telephone number is 573-884-2696.  For more information about risks and side effects, ask the 
investigator or contact Zach Holliday at 573-884-2696 


 
 
 
 
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• Dornase alfa risks: In other studies, the side effects that other people have experienced 
so far with dornase alfa are: rash, temporary voice change, or very rarely, anaphylactic 
reaction to the drug.  
• Blood testing risks: Taking blood from you may cause some discomfort from the needle 
stick, bruising, or very rarely, infection. 
• Procedural risks: Performed flexible bronchoscopy with bronchoalveolar lavage has a 
small risk of airway trauma, fever, infection, or very rarely, pneumothorax.  
• Unknown risks: The experimental drug in this study may have side effects that no one 
knows about yet. The study team will tell you if they learn anything that might make you 
change your mind about being in the study. 
 
ARE THERE BENEFITS TO TAKING PART IN THE STUDY? 
We don’t know if this study will help you. Your condition may get better, but it could stay the 
same or even get worse. We hope the drug will improve the respiratory status of those on 
mechanical ventilation related to SARS-CoV-2 and reduce the number of days on mechanical 
ventilation, days in the hospital and mortality. We hope that this study will help us to learn more 
about SARS-CoV-2 pneumonia and respiratory failure/ARDS, and to develop new treatments for 
respiratory failure/ARDS related to SARS-CoV-2 in the future. 
 
WHAT OTHER CHOICES DO I HAVE? 
You do not have to take part in this study. You are free to say yes or no. If you do not want to 
join this study, your doctor will discuss other choices with you. 
 
Your other choices include: 
• There is no known effective treatment for your condition, but there are cares deemed 
standard of care for your condition 
• Joining another research study 
• The drug offered on this study may also be available to you without being in this study 
• Not joining this study and continuing your regular medical care 
 


 
 
 
 
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The study doctor can discuss the possible benefits and risks of the other options available to you. 
 
WHAT ABOUT PRIVACY AND CONFIDENTIALITY? 
The study team needs to access/collect/use some of your health/personal information. This 
information comes from questions we ask you, forms you fill out, and/or your medical record. 
One risk of taking part in a research study is that more people will handle your personal health 
information. We are committed to respecting your privacy and to keeping your personal 
information confidential. The study team will make every effort to protect your information and 
keep it confidential to the extent allowed by law. However, it is possible that an unauthorized 
person will see it.  
 
State and federal privacy laws (HIPAA) protect the use and release of your health information. If 
you decide to take part in this study, you also give us your permission to use your private health 
information, including the health information in your medical records and information that can 
identify you.  
You have the right to refuse to give us your permission for us to use your health information. 
However, doing so would mean that you could not take part in this study.  
 
The following identifiers will be obtained from your health records: 
Name 
 
 
 
 
 
Address 
Dates related to you 
 
 
 
Telephone number(s) 
Fax Number 
 
 
 
 
Email Address 
Social Security Number 
 
 
 
Medical Record Number 
Health Plan Beneficiary Number  
 
Account Numbers 
Certificate or License Numbers 
 
 
Any vehicle or device serial number 
Web Address (URL) 
 
 
 
Internet Protocol (IP) Address(es) 
Biometric Identifiers (finger/voice print)  
Photographic images 
Any other characteristic that could identify you 
 
The following is the type of protected health information that will be used in the study:  
Radiology Images  
 
 
 
Discharge Summaries 


 
 
 
 
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Radiology Reports  
 
 
 
Health Care Billing or Financial Records 
EKG Recordings/Reports  
 
 
Consultations 
Progress Notes 
 
 
 
 
Medications 
History and Physical Exams 
 
 
Emergency Medicine Reports 
Operative Reports  
 
 
 
Dental Records 
Pathology Reports  
 
 
 
Demographics (age, race, etc.) 
Laboratory Reports 
 
 
 
Questionnaires, Surveys, Diaries 
Photographs/Video Recordings 
 
 
Audio Recordings 
Social Security Number (This is only collected for billing/payment purposes and will not be 
shared with the study sponsor) 
Other: 
 
Certain sensitive information about you can only be released if you give your specific 
permission. This includes information such alcohol or drug abuse, HIV/AIDS testing, and mental 
health records. We will ask you to indicate your permission to release this information at the end 
of this consent form. This is your specific permission for release of this information. Federal 
rules do not allow any use of the information to criminally investigate or prosecute any alcohol 
or drug abuse. Federal rules do not allow any use of the information to criminally investigate or 
prosecute any alcohol or drug abuse. 
 
We may share any of this information with the following:  
• Authorized members and staff of the University of Missouri Institutional Review Board 
(IRB).  
• Laboratories and other individuals and organizations that may need to see your health  
information in connection with this study. 
• Study monitors and auditors who make sure that the study is being done properly.  
• Government agencies and public health authorities, such as the Food and Drug  
Administration (FDA), the Department of Health and Human Services (DHHS), and the 
Office for Human Research Protections (OHRP) 
 


 
 
 
 
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Any research information shared with outside entities will not contain your name, address, 
telephone or social security number, or any other personal identifier unless it is necessary for 
review or required by law. 
The people who get your health information may not be required by Federal privacy laws (such 
as the HIPAA Privacy Rule) to protect it. Some of those people may be able to share your 
information with others without your separate permission. 
 
Your permission for us to use and/or release your information will last until 2 years after 
completion of the study unless you cancel your permission.  
 
 
 
You can cancel your permission at any time by writing to:  
Investigator’s Name: Zach Holliday 
Institution: University of Missouri 
Department: Internal Medicine 
Address: 1 Hospital Dr., Columbia, MO, 65212 
 
The information we have already collected may still be used for this research study, but we will 
not collect anymore information after we receive your letter.  
 
You will not be allowed to access your protected health information that is obtained or created 
during this research project until the end of the study. 
 
If you have not already received a copy of the University of Missouri Healthcare Privacy Notice, 
you may request one. If you have any questions or concerns about your privacy rights, you may 
contact the Privacy Officer at 573-882-9054. 
 
We will scan a copy of this consent form into your medical record. We may also record your 
research information, including the results of tests and procedures, in your medical record. The 


 
 
 
 
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medical information produced by this study will become part of your hospital medical record, 
and people allowed to look at your medical records may see this research information.  
 
Information that does not become part of your medical record will be stored in the investigator’s 
electronic/computer or paper files. Computer files are protected with a password and the 
computer is in a locked office that only study team members can open. Paper files are kept in a 
locked drawer in a locked office that only study team members can open. 
 
Your records will be given a code number and will not contain your name or other information 
that could identify you.  The code number that connects your name to your information will be 
kept in a separate, secure location.  Information that may identify you may not be given to 
anyone who is not working on this study without your written consent, or if required by law.   
 
The people who may use and/or release your research information include: 
• Those working on the study team at the University of Missouri 
• The members of the University of Missouri Institutional Review Board (IRB) 
• Those who check on research activities to make sure it is being done correctly and safely  
• The FDA  
• Other government or inspection agencies  
 
If the study investigator is not your regular doctor, he/she must ask your permission before 
contacting your regular doctor for your health history. 
 
We may present the results of this study in public talks or written articles, but we will not use 
information that can identify you.   
 
ARE THERE ANY COSTS TO BEING IN THE STUDY? 
 
There is no additional cost to you for taking part in this study. 


 
 
 
 
MU IRB: BIOMEDICAL CONSENT FOR FEDERALLY FUNDED  
RESEARCH, CLINICAL TRIALS, AND/OR GREATER THAN MINIMAL 
RISK RESEARCH 
(JAN 2019) 
 
 
 
12 of 16
HS IRB USE ONLY 
Approval Date:  
The study will pay for all research tests and performed flexible bronchoscopy with fluid analysis 
that is not part of your routine clinical care.  
You and/or your health plan/insurance will be billed for all other tests and procedures you need 
for your routine health care while you are in this study.  
 
Some health plans/insurance companies will not pay for these costs for people who are in 
research studies. Check with your health plan/insurance company to find out what they will pay 
for. If you have any questions about which tests/procedures will be billed to you and/or your 
health plan/insurance, please ask us. 
 
 
WILL I BE PAID FOR TAKING PART IN THIS STUDY? 
There is no payment to you for taking part in this study. 
 
 
Possible Commercial Products 
All tissue and body fluid samples are important to this research study. Your samples will be 
owned by University of Missouri. These people may make products from this study that can be 
sold. If they sell these products, you will not receive any money.  
 
 
 
WHAT HAPPENS IF I AM INJURED DURING THE STUDY?  
It is not the policy of the University of Missouri to compensate human subjects in the event the 
research results in injury.  The University of Missouri, in fulfilling its public responsibility, has 
provided medical, professional and general liability insurance coverage for any injury in the event 
such injury is caused by the negligence of the University of Missouri, its faculty and staff.   
The University of Missouri also will provide, within the limitations of the laws of the State of 
Missouri, facilities and medical attention to subjects who suffer injuries while participating in the 
research projects of the University of Missouri.   
 


 
 
 
 
MU IRB: BIOMEDICAL CONSENT FOR FEDERALLY FUNDED  
RESEARCH, CLINICAL TRIALS, AND/OR GREATER THAN MINIMAL 
RISK RESEARCH 
(JAN 2019) 
 
 
 
13 of 16
HS IRB USE ONLY 
Approval Date:  
In the event you have suffered injury as the result of participation in this research program, you are 
to contact the Risk Management Officer, telephone number (573) 882-1181, at the Health Sciences 
Center, who can review the matter and provide further information.   
This statement is not to be construed as an admission of liability. 
 
 
WHAT ARE MY RIGHTS AS A STUDY PARTICIPANT? 
Taking part in this study is voluntary.  You do not have to take part.  Your present or future 
medical care will not be affected if you decide not to take part.   
 
If you do decide to take part, you can change your mind and drop out of the study at any time. 
This will not affect your current or future care at the University of Missouri Hospitals and 
Clinics. There is no penalty for leaving the study and you will not lose any benefits that you are 
entitled to receive. 
 
If the study investigator decides to take you off the study, he/she will explain the reasons and 
help arrange for your continued care by your own doctor, if needed.   
 
We will tell you about any new information discovered during this study that might affect your 
health, welfare, or change your mind about taking part.  
 
 
WHERE CAN I GET MORE INFORMATION ABOUT THIS STUDY? 
 
A description of this clinical trial will be available on www.ClinicalTrials.gov, as required by 
U.S. law. This Web site will not include information that can identify you. At most, the Web site 
will include a summary of the results. You can search this Web site at any time. 
 
WHO CAN ANSWER MY QUESTIONS ABOUT THE STUDY? 
If you have more questions about this study at any time, you can call Dr. Holliday at 573-884-
2696. 


 
 
 
 
MU IRB: BIOMEDICAL CONSENT FOR FEDERALLY FUNDED  
RESEARCH, CLINICAL TRIALS, AND/OR GREATER THAN MINIMAL 
RISK RESEARCH 
(JAN 2019) 
 
 
 
14 of 16
HS IRB USE ONLY 
Approval Date:  
You may also contact the University of Missouri Institutional Review Board (IRB) if you: 
• Have any questions about your rights as a study participant; 
• Want to report any problems or complaints; or 
• Feel under any pressure to take part or stay in this study.  
 
The IRB is a group of people who review research studies to make sure the rights of participants 
are protected. Their phone number is 573- 882-3181.  
 
If you want to talk privately about your rights or any issues related to your participation in this 
study, you can contact University of Missouri Research Participant Advocacy by calling 888-
280-5002 (a free call), or emailing MUResearchRPA@missouri.edu. 
 
We will give you a copy of this consent form. Please keep it where you can find it easily. It will 
help you to remember what we discussed today. 
 
 
 
 
SIGNATURE OF STUDY PARTICIPANT  
My initials below indicate my choice about the optional tests in this study: 
 
I agree to the optional flexible bronchoscopy with bronchoalveolar lavage 
 
 
Yes ___________ 
 
No ____________ 
 
 
 
My initials below indicate my choice about using my data/samples for future research: 
 
 
My data/samples may be stored and used for future research. 
 
 
Yes ___________ 
 
No ____________ 
 
My initials below indicate my permission to release the sensitive information listed below:  
____I agree to the release of information about drug and alcohol abuse, diagnosis or treatment. 


 
 
 
 
MU IRB: BIOMEDICAL CONSENT FOR FEDERALLY FUNDED  
RESEARCH, CLINICAL TRIALS, AND/OR GREATER THAN MINIMAL 
RISK RESEARCH 
(JAN 2019) 
 
 
 
15 of 16
HS IRB USE ONLY 
Approval Date:  
____I agree to the release of HIV/AIDS testing information. 
 
Consent to Participate in Research 
 
By signing my name below, I confirm the following: 
• I have read/had read to me this entire consent form. 
• All of my questions were answered to my satisfaction. 
• The study’s purpose, procedures, risks and possible benefits were explained to me. 
• I voluntarily agree to take part in this research study. I have been told that I can stop at 
any time. 
 
 
 
Subject’s Signature 
Date  
 
 
 
 
 
 
SIGNATURE OF PERSON AUTHORIZED TO OBTAIN CONSENT*  
I have explained the purpose of the research, the study procedures (identifying those that are 
investigational), the possible risks and discomforts and potential benefits of the study, and have 
answered questions regarding the study to the best of my ability. 
 
 
 
 
 
IF THE PARTICIPANT IS DECISIONALLY IMPAIRED, THE LEGALLY AUTHORIZED 
REPRESENTATIVE (LAR) SHOULD READ AND SIGN BELOW: 
 
By signing my name below, I confirm the following: 
• I have read/had read to me this entire consent form. 
• All of my questions were answered to my satisfaction. 
• The study’s purpose, procedures, risks and possible benefits were explained to me. 
 
 
 
Signature of Witness (if applicable)* 
Date  
 
 
 
Signature of Person Authorized to Obtain Consent 
Date  


 
 
 
 
MU IRB: BIOMEDICAL CONSENT FOR FEDERALLY FUNDED  
RESEARCH, CLINICAL TRIALS, AND/OR GREATER THAN MINIMAL 
RISK RESEARCH 
(JAN 2019) 
 
 
 
16 of 16
HS IRB USE ONLY 
Approval Date:  
• I voluntarily agree to this participant taking part in this research study. I have been told 
that they can stop participating at any time. 
 
 
 
Signature of legally authorized representative 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
MO Rev Stat 431.064: Experimental treatment, tests, and drugs, consent to administer by third party — life-
threatening emergencies, consent by whom. —  
1. When an adult person, because of a medical condition, is treated by a teaching hospital for a medical school 
accredited by the American Osteopathic Association or the American Medical Association and such person is 
incapable of giving informed consent for an experimental treatment, test or drug, then such treatment, test or drug 
may proceed upon obtaining consent of a legal guardian, attorney-in-fact, or a family member in the following 
order of priority: 
(1) Spouse unless the patient has no spouse, or is separated, or the spouse is physically or mentally incapable of 
giving consent, or the spouse's whereabouts is unknown or the spouse is overseas; 
(2) Adult child; 
(3) Parent; 
(4) Brother or sister; 
(5) Relative by blood or marriage. 
 
2. Nothing in this section shall authorize such legal guardian, attorney-in-fact, or family member to consent to 
treatment in contravention to such incapacitated person's expressed permission regarding such treatment. 
 
 (L. 1993 H.B. 564 § 33, A.L. 2003 S.B. 431, A.L. 2006 H.B. 1601 merged with S.B. 765) 
 
 
 
 
Relationship of LAR to Participant 
Date  
 
 
 
Signature of Witness 
Date  
 
 
 
Signature of Person Authorized to Obtain Consent* 
Date