Randomized Controlled Trial of Autologous Microbiome Reconstitution to Prevent Colonization by Antibiotic rEsistant Bacteria
Phase: PHASE1
Conditions: Antibiotic Resistant Strain
Sponsor: Microbiome Health Research Institute

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RACE: 
Randomized controlled trial of Autologous microbiome reconstitution to prevent 
Colonization by antibiotic rEsistant bacteria 
 
 
 
 
 
 
 
ClinicalTrials.gov Identifier: NCT03061097  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Statement of Compliance 
 
The study will be carried out in accordance with Good Clinical Practices (GCP) 
as required by the following: 
1. United States Code of Federal Regulations (CFR) applicable to clinical 
studies (45 CFR Part 46; 21 CFR Part 50, 21 CFR Part 54, 21 CFR Part 56, 
and 21 CFR Part 312); 
2. International Conference on Harmonization (ICH) E6; 62 Federal 
Register 25691 (1997); 
Compliance with these standards provides public assurance that the rights, 
safety and well-being of study subjects are protected, consistent with the 
principles that have their origin in the Declaration of Helsinki. 
 
All key personnel (all individuals responsible for the design and conduct of this 
study) have completed Human Subjects Protection Training. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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PRINCIPAL CLINICIAN SIGNATURE PAGE 
 
 
 
Protocol Title:  
Randomized controlled trial of Autologous microbiome 
reconstitution to prevent Colonization by antibiotic 
rEsistant bacteria 
 
 
Version Date:  
17 September 2019 
 
 
I acknowledge that I have read and understand the protocol named above 
and agree to conduct the study according to the protocol named above. I also 
agree and will adhere to terms and procedures in accordance with United 
States Food and Drug Administration (FDA)/International Council for 
Harmonisation (ICH) guidelines, including all federal and locally applicable 
regulations and laws. 
 
I assure that the study drug supplied by OpenBiome will be used only as 
described in the protocol named above. 
 
 
 
 ____________________________________________  
 _________________________  
 
 
Signature  
Date 
 
 
 
 ____________________________________________  
 
Print Name 
 
 
 
 
 
 
 
 
 

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APPENDIX C: TABLE OF CONTENTS 
Statement of Compliance ....................................................................................................... 2 
C.1. List of Abbreviations ......................................................................................................... 8 
C.2. Protocol Summary .......................................................................................................... 10 
C.3. Key Roles ........................................................................................................................ 13 
C.4. Background Information and Scientific Rationale ...................................................... 15 
C.4.1. Background Information .............................................................................................15 
C.4.1.1 Fecal Microbiota Transplantation for the Treatment of Recurrent 
Clostridium difficile Infection and Other ARB ............................................................15 
C.4.1.2. Rationale ........................................................................................................17 
C.4.1.3. Potential Impact ............................................................................................17 
C.4.2 Potential Risks and Benefits ..........................................................................................17 
C.4.2.1. Potential Risks .................................................................................................17 
C.4.2.2. Insufficient Enrollment Risk .............................................................................18 
C.4.2.3. Safety Risks .....................................................................................................18 
C.4.2.4. Baseline Geriatric Microbiome Risk ..............................................................19 
C.4.2.5. Known Potential Benefits...............................................................................19 
C.5. Objectives ...................................................................................................................... 20 
C.5.1 Study Objective ............................................................................................................20 
C.5.1.1. Study Objective .............................................................................................20 
C.5.1.2. Primary Objectives.........................................................................................20 
C.5.1.3. Secondary Objectives ..................................................................................20 
C.5.2. Endpoints ......................................................................................................................20 
C.5.2.1. Primary Endpoint ............................................................................................20 
C.5.2.2. Secondary Endpoints ....................................................................................20 
C.5.2.3. Possible Exploratory Endpoints ......................................................................21 
C.6. Study Design ................................................................................................................... 22 
C.6.1. Study Population ..........................................................................................................22 
C.6.2. Intervention...................................................................................................................22 
C.6.2.1. Dosing Rationale ...........................................................................................22 
C.6.3. Control ..........................................................................................................................22 
C.7. Inclusion and Exclusion Criteria .................................................................................... 23 
C.7.1. Inclusion Criteria ...........................................................................................................23 
C.7.1.1. Inclusion Criteria for Study Enrollment ..........................................................23 
C.7.1.2. Inclusion Criteria for Randomization ............................................................23 
C.7.2. Exclusion Criteria ..........................................................................................................23 
C.7.2.1. Exclusion Criteria for Study Enrollment .........................................................23 
C.7.2.2. Exclusion Criteria for Stool Collection ...........................................................23 
C.7.2.3. Exclusion Criteria for Randomization ............................................................24 
C.8. Treatment Assignment Procedures ............................................................................... 25 
C.8.1. Randomization Procedures .........................................................................................25 

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C.8.2. Masking Procedure ......................................................................................................25 
C.8.3. Interim Analysis .............................................................................................................25 
C.8.4. Participant Withdrawal ................................................................................................26 
C.8.5. Procedure for Handling Participant Withdrawal .......................................................26 
C.8.6. Study Termination .........................................................................................................26 
C.9. Study Interventions / Investigational Drug ................................................................... 27 
C.9.1. Interventional Product Description .............................................................................27 
C.9.1.1. Autologous Treatment Preparation .............................................................27 
C.9.1.2. Fecal Microbiota Transplant (FMT) ...............................................................27 
C.9.2. Formulation ...................................................................................................................27 
C.9.2.1. Auto-FMP Enema ...........................................................................................27 
C.9.2.2. Placebo Enema Preparation ........................................................................27 
C.9.3. Product Storage and Stability .....................................................................................27 
C.9.3.1. Auto-FMP Enema Preparation ......................................................................27 
C.9.4. Dosage, Preparation and Administration of Study Intervention ..............................28 
C.9.4.1. Auto-FMP Enema ...........................................................................................28 
C.9.5. Accountability Procedures for the Study Intervention/Investigational Product(s) .28 
C.9.6. Assessment of Participant Compliance with Study Intervention/Investigational 
Product ....................................................................................................................................28 
C.9.7. Concomitant Medications/Treatments......................................................................28 
C.9.8. Screening Visit and Patient Information (Visit 1) ........................................................29 
C.9.9. Collection and Processing (Visit 2) .............................................................................30 
C.9.10. Surveillance for Infectious Episodes ..........................................................................30 
C.9.11. Infectious Episode (Visit 3) .........................................................................................31 
C.9.12. Post-Antibiotic Stool Collection (Visit 4) ....................................................................31 
C.9.13. FMT Study Visit (Visit 5) ................................................................................................32 
C.9.13.1. Pre-FMT Procedure ......................................................................................32 
C.9.13.2. FMT Procedure: Day 0 .................................................................................33 
C.9.13.3. Post- FMT Procedure ....................................................................................33 
C.9.14 Follow-Up (Visit 6, 7, 8, 9) .............................................................................................33 
C.9.14.1. Study Visit 6: Day 3 Post-FMT (+/- 1 Day) ....................................................33 
C.9.14.2. Study Visit 7: Day 7 post-FMT (+/- 2 Day) - Primary End Point ...................34 
C.9.14.3. Study Visit 8: Day 28 (+/- 5 Day) - Intermediate Safety Assessment ........34 
C.9.14.4. Study Visit 9: Month 6 (+/- 14 Day) - Long Term Safety Assessment .........35 
C.9.15. Early Termination Visit .................................................................................................35 
C.9.16. Unscheduled Study Visit ............................................................................................36 
C.10. Study Procedures / Evaluations .................................................................................. 37 
C.10.1. Clinical Evaluation at Enrollment ..............................................................................37 
C.10.2. Evaluation at Follow-Up Study Visits ..........................................................................37 
C.10.3. Evaluation of Safety Outcome .................................................................................37 
C.10.4. Laboratory Evaluations ..............................................................................................37 
C.10.4.1. Enrollment .....................................................................................................37 
C.10.4.2. Screening Only Samples .............................................................................37 
C.10.4.3. Samples Processed into Enemas ................................................................38 

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C.10.4.4.Study Visit Stool Collection ...........................................................................38 
C.10.4.5. Rectal Swabs ...............................................................................................38 
C.10.5. Specimen Handling and Shipping ............................................................................38 
C.11. Assessment of Safety ................................................................................................... 40 
C.11.1. Definition of Adverse Events (AE) ..............................................................................40 
C.11.2. NIH Grading of Severity of the Event ........................................................................40 
C.11.3. Relatedness ................................................................................................................41 
C.11.4. Solicited Adverse Events After Auto-FMP .................................................................41 
C.11.5. Serious Adverse Events ..............................................................................................42 
C.11.6. Unsolicited Adverse Events ........................................................................................43 
C.11.7. Reporting of Adverse Events .....................................................................................43 
C.11.8. Follow-up of Participants After Adverse Events .......................................................45 
C.11.9. Halting Rules ...............................................................................................................45 
C.11.9.1. Study Halting Rules ......................................................................................45 
C.11.9.2. Individual’s Halting Rules .............................................................................45 
C.11.10. Safety Oversight .......................................................................................................46 
C.11.10.1 Data and Safety Monitoring Board (DSMB) ..............................................46 
C.12. Clinical Monitoring ....................................................................................................... 47 
C.12.1. Site Monitoring Plan ...................................................................................................47 
C.13. Statistical Considerations ............................................................................................ 48 
C.13.1. Study Objectives ........................................................................................................48 
C.13.2. Primary Endpoint of Short-Term Safety .....................................................................48 
C.13.3. Secondary Endpoints .................................................................................................48 
C.13.3.1.Clearance of ARB Among Patients Co-colonized at Day 3, Day 7, and 
Day 28 ..........................................................................................................................48 
C.13.3.2. Proportion Of Participants Who Develop ARB Associated Infections at 
Day 3, Day 7, Day 28, And Month 6 ..........................................................................48 
C.13.3.3. Proportion of Participants Who Develop AE’s by Day 28 .........................48 
C.13.4. Possible Exploratory Endpoint ...................................................................................48 
C.13.4.1. Microbiome Disruption Indices (16S rRNA sSequencing) ..........................48 
C.13.5. Sample Size .................................................................................................................49 
C.13.6. Final Analysis Plan .......................................................................................................49 
C.14. Source Documents and Access to Source Data/Documents .................................. 51 
C.15. Quality Control and Quality Assurance ..................................................................... 52 
C.15.1. Procedural Quality Control .......................................................................................52 
C.15.2. Database Quality Control .........................................................................................52 
C.16. Ethics/Protection of Human Participants .................................................................... 53 
C.16.1. Ethical Standard .........................................................................................................53 
C.16.2. Institutional Review Board .........................................................................................53 
C.16.3. Informed Consent Process ........................................................................................53 
C.16.4. Exclusion of Women, Minorities, and Children (Special Populations) ....................55 
C.16.5. Participant Confidentiality ........................................................................................55 

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C.16.6. Study Discontinuation ................................................................................................55 
C.16.7. Future Use of Stored Specimens ...............................................................................56 
C.16.8. Data Management Responsibilities ..........................................................................56 
C.16.9. Data Capture Methods .............................................................................................57 
C.16.10. Types of Data ...........................................................................................................57 
C.16.11. Timing/Reports ..........................................................................................................57 
C.16.12. Study Records Retention .........................................................................................57 
C.16.13. Protocol Deviations ..................................................................................................57 
C.17. References .................................................................................................................... 59 
C.18. Safety Reporting and Definitions ................................................................................. 63 
C.18.1. Investigational New Drug Safety Reporting Definitions ...........................................63 
C.18.2. Sample Adverse Event Reporting Form with NIH Severity Grading Scale .............64 
C.18.3. Adverse Event Assessment Flowchart ......................................................................65 
C.19. Study Design ................................................................................................................. 66 
C.19.1. Study Design Schematic ............................................................................................66 
C.19.2. Patient Enrollment Pipeline ........................................................................................67 
C.19.3. Study Schedule ..........................................................................................................68 
C.20. Common Conditions in the Geriatric Population ...................................................... 69 
 
 
 

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C.1. List of Abbreviations 
 
AE 
Adverse event 
ARB 
Antibiotic resistant bacteria 
BU-BMC 
Boston University – Boston Medical Center 
CDC 
Centers for Disease Control and Prevention 
CDI 
Clostridium difficile Infection 
CNA 
Certified nurse assistant  
CRE 
Carbapenem-resistant Enterobacteriaceae 
CRF 
Case report form 
DSMB 
Data and safety monitoring board 
eCRF 
Electronic case report form 
EIA 
Enzyme Linked ImmunoAssay 
ESBL 
Extended spectrum beta-lactamase producing organisms 
FMP 
Fecal microbiota product 
FMT 
Fecal Microbiome Transplant 
GCP 
Good clinical practice 
ICH 
International Conference on Harmonisation 
IND 
Investigational new drug 
IRB 
Institutional review board 
MDI 
Microbiome disruption indices 
MIT 
Massachusetts Institute of Technology 
NIH 
National Institute of Health 
NPO 
Nil per os / fasting 
OTU 
Operational taxonomic unit 
PCR 
polymerase chain reaction 
PI  
Principal investigator 
QA 
Quality assurance 
QC  
Quality control 
RACE 
Randomized controlled trial of Autologous microbiome 
reconstitution to prevent Colonization by antibiotic 
rEsistant bacteria (RACE) trial 
SAE 
Severe adverse event 
SOP 
Standard operating procedure 
VRE 
Vancomycin-resistant enterococci 
 
 
 
 
 

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C.2. Protocol Summary 
 
Title 
Randomized controlled trial of Autologous microbiome 
reconstitution to prevent Colonization by antibiotic rEsistant 
bacteria (RACE) trial 
Phase 
I/II 
Population 
Stool collection from long-term care facility residents 
(n=180) 
 
Key inclusion criteria: 
1. Long-term care residents associated with Boston 
University-Boston Medical Center nursing home 
consortium 
2. Adults (18 years or older) 
 
Key exclusion criteria: 
• Colostomy 
• Hospice 
 
Target sample size of n= 20* (14 in the FMT group and 6 in 
the placebo group, randomized 2:1) participants who 
develop an infection requiring antibiotic therapy. 
 
* Based on antibiotic resistant bacteria (ARB) prevalence 
and care-facility infection rates. 
Number of sites 
Up to 4 long-term care facilities in greater Boston area 
Study duration 
18 months 
Intervention 
Autologous fecal microbiota preparation, collected at 
enrollment, administered by enema delivery vehicle 
Study objectives 
To investigate the safety, feasibility and the role of 
autologous fecal microbiota transplantation (FMT) for the 
prevention of antibiotic resistant bacteria (ARB) through 
microbiome restoration. 
 
Primary objective: 
To evaluate the safety and feasibility of autologous FMT 
administered by enema delivery in an elderly, long-term 
care population. 
 
Secondary objectives: 

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1. Evaluate changes in microbial communities’ pre-
infection, post-antibiotic exposure and following FMT 
administration 
2. To examine the effect of autologous FMT on ARB 
colonization and associated infection 
Study endpoints 
Primary endpoint:  
• Safety (short-term) at Day 7 defined as NIH Grade 
≥2 adverse events 
 
Secondary endpoints: 
• Among patients with ARB colonization at Day 0 
(post-antibiotics), rate of ARB clearance at Day 3, 
Day 7, and Day 28 
o Carbapenem-resistant Enterobacteraciae 
(CRE) by PCR or culture-based assay 
o Extended spectrum beta-lactamase (ESBL)-
producing organisms by PCR or culture-based-
assay 
o Vancomycin-resistant enterococci (VRE) by 
PCR or culture-based assay 
o Clostridium difficile by PCR 
• Composite endpoint for presence of any ARB-
associated clinical infection at Day 3, Day 7, Day 28, 
and Month 6. 
• Safety (intermediate at Day 28 and long-term at 
Month 6) defined as NIH Grade ≥2 adverse events. 
 
Possible exploratory endpoint: 
• Microbiome disruption indices (16S rRNA 
sequencing): MDI-community and MDI-species at 
baseline (pre-infection on the date of stool 
collection), post-antibiotics on the 
intervention/placebo date (Day 0, Day 3, Day 7, and 
Day 28). MDI will be applied to pre- and post-
intervention communities in comparison to baseline 
and reference communities. 
 

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Study design 
A pilot, randomized, double-blind, placebo-controlled trial 
to assess the safety and feasibility of autologous FMT, its 
effect on the intestinal microbiome and the prevention of 
ARB colonization and infection. 
 
In order to yield the target sample size of n=20 participants 
who develop an infection requiring antibiotics, a total of 
180 participants will be enrolled for stool collection. After 
completion of the antibiotic course, participants (n=20) will 
be randomized (2:1) to placebo or autologous FMT enema 
if eligible. Once the antibiotics have finished and at least 
72 hours have passed, a  pre-FMT stool sample or rectal 
swabs will be collected. Both trial arms will have the 
treatment or placebo administered at least 72 hours post-
antibiotics (± renal/hepatic adjustment at the discretion of 
the treating physician to ensure specific antibiotics has 
been cleared and will not impact FMT). 
 
Follow-up: Follow-up and sample collection will occur at 
Day 3 (±1 day), Day 7 (±2 days), and Day 28 (±5 days). 
Additional follow-up for safety will occur at Month 6 (±14 
days) including a stool sample. All samples will be analyzed 
for 1) presence of ARBs using a PCR test and 2) 16S rRNA 
sequencing. 
 
 
 

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Data Analyst: Pratik Panchal, MD, 
MPH 
 
 
 

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C.4. Background Information and Scientific Rationale 
C.4.1. Background Information 
Antibiotic-resistant bacteria (ARB) pose an urgent public health threat, with over 
2 million Americans infected each year.1 Over half of these infections are 
transmitted in healthcare settings, where the widespread use of antibiotics 
selects for resistance and creates a stable pool of vectors, enabling the 
transmission of resistant organisms.1 
 
Elderly residents of long-term care facilities are particularly vulnerable to ARB 
colonization, and in turn, infection.2 Geriatric populations are commonly frail, 
immunocompromised and often possess multiple co-morbidities that increase 
their risk of infections.2 Furthermore, communal assisted living and frequent 
transfer between long-term residential facilities and acute care settings facilitate 
microbial transmission between high-ARB environments.2 
 
Antibiotic exposure is one of the greatest risk factors for ARB acquisition.3,4 While 
rates vary across facilities, up to 70% of nursing home residents receive at least 
one course of antibiotics per year, a rate approximately twice that of the 
general population.5,6 Exposure to antibiotics results in an immediate and 
substantial perturbation of the gut microbiome with only partial recovery of 
original taxonomic composition.7 A common working hypothesis is that intact 
microbial communities competitively exclude exogenous microbiota, providing 
‘colonization resistance.’ This hypothesis is supported by research that indicates 
disruption of the resident microbiota with antibiotics decreases the minimum 
infective dose and increases the colonization potential of enteric 
pathogens.8,9,10,11 
 
Efforts to decrease ARB transmission through infection control strategies and 
antimicrobial stewardship are underway; however, they have proven both 
expensive and ineffective.5 Point-prevalence studies report up to 43% of nursing 
home residents are colonized with at least one ARB at any given time, 
contributing to a high potential for dissemination.3 This reservoir of ARB in an 
already vulnerable population contributes to an estimated 23,000 ARB infection 
deaths and $20 billion in direct costs to the U.S. healthcare system annually.1 
 
C.4.1.1 Fecal Microbiota Transplantation for the Treatment of Recurrent 
Clostridium difficile Infection and Other ARB 
Allogeneic fecal microbiota transplantation (FMT), the introduction of colonic 
microbiota from a healthy donor into patients with gut dysbiosis, has been 
shown to be a highly effective and safe intervention for treatment of recurrent 
Clostridium difficile infection (CDI). A recent systematic review and pooled 

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analysis reports FMT as 83% effective in treatment of recurrent CDI, which 
commonly impacts the geriatric population, with few reported adverse 
events.12,13 A recent large case series of 146 elderly recurrent CDI patients 
supports the relative safety of allogeneic FMT.12,13 Although not fully elucidated, 
the hypothesized mechanism of FMT for CDI is that normal colonic microbiota 
outcompete and thereby competitively exclude C. difficile.14 
 
A recent commentary by Halpin and McDonald of the Centers for Disease 
Control and Prevention (CDC) highlights the ecological principles and 
preliminary research suggesting FMT may also be effective for eliminating 
enteric colonization with ARB such as vancomycin-resistant enterococci (VRE).15 
Similar to CDI, VRE colonization is known to be induced by microbial dysbiosis.16 
Furthermore, vancomycin-resistance is known to carry a fitness defect for the 
organism carrying this gene, making it a prime target for microbial intervention 
such as FMT that introduces new microbes that may competitively exclude VRE. 
In vitro competition assays with enterococci have demonstrated a 4% fitness 
defect of VanA relative to sensitive enterococci.17 Similarly, expression of VanB-
type resistance results in reduced fitness in vitro, as well as reduced colonization 
ability and dissemination in gnotobiotic mice.18 In another murine study, the 
transfer of healthy colonic microbiota from antibiotic-naive mice has been 
shown to reverse dysbiosis and eliminate VRE infection within 14 days.19 
 
In addition to this translational work, a number of case reports have suggested 
that FMT may be able to decolonize patients colonized with ARB. Several case 
reports have reported de-colonization of ARB following FMT, including 
carbapenem-resistant Enterobacteraciae (CRE), extended spectrum beta-
lactamase (ESBL)-producing Escherichia coli and methicillin-resistant 
Staphylococcus aureus (MRSA) enteritis.20,21,22,23,24 Our group has submitted work 
that supports the role of FMT for VRE decolonization (see Eysenbach et al. 
IDWeek 2016, Appendix A.2.). Our group performed a multicenter retrospective 
analysis was performed using stool samples from recurrent CDI patients treated 
with FMT (n=31) or autologous FMT as a control from a previous trial (n=18). VRE 
was assessed using a PCR-based assay targeting VanA (Acuitas® MDRO Gene 
Test). Colonization was defined as positive result at any dilution. VRE 
decolonization was defined as absence of VRE colonization post-FMT among a 
patient colonized with VRE pre-FMT. Among this cohort, 16 patients were VRE 
colonized; 9/9 (100%) in the FMT group tested VRE-negative compared to 3/7 
(43%) in the control group (p=0.02, Fisher's Exact Test). Two of these patients 
were treated with a single dose of 30 FMT capsules, while the rest received FMT 
via traditional modalities. 
 

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C.4.1.2. Rationale 
OpenBiome’s universal donors have been rigorously screened for both infectious 
and potentially microbiome-mediated chronic disease resulting in a 
qualification of only 2.8% of candidate donors.25 Additionally, among a large, 
multi-center cohort (n=2,050) who received allogeneic FMT from OpenBiome to 
treat C. difficile infection not responsive to standard therapy, only 42 adverse 
events (AE) were reported, none of which were determined to be “definitely 
related” to FMT. Three were “possibly related” to FMT and 39 cases were “not 
related” based on NIH criteria, suggesting a favorable short-term safety profile 
(See Osman et al. IDWeek 2016, Appendix A.1.). Despite this data, there remains 
important, yet theoretical, long-term risks associated with such a dramatic 
manipulation of the microbiome and the risk of transmitting currently unknown 
or untestable pathogens or other risk factors.26 For critically ill patients or those 
without effective treatment alternatives, such a risk is justified, but clinical 
equipoise becomes more challenging if FMT is to be used as a prophylactic 
intervention, for example, to restore colonization resistance following antibiotic 
exposure as a novel infection control and public health tool. 
 
Accordingly, the use of autologous FMT, using fecal material collected from a 
patient at a previous time of relative health may significantly reduce the risks of 
FMT by limiting the recipient’s exposure to exogenous organisms and restoring 
their own healthy microbial community. The logistical feasibility of autologous 
FMT has been validated by OpenBiome’s PersonalBiome program and an 
ongoing pilot among bone marrow transplant recipients.27  
 
C.4.1.3. Potential Impact 
By mitigating the potential risks of allogenic FMT from universal donors, 
autologous prophylactic FMT carries with it transformative possibilities in 
addressing the threat presented by ARB. Should this trial suggest safety and yield 
promising translational results, we would plan to follow up with a fully-powered 
randomized controlled trial that has the potential to suggest prophylactic 
autologous FMT as a novel public health tool for preventing enteric ARB 
infections among high-risk patients. We envision a future where autologous FMT 
emerges to enable microbiome reconstitution following antibiotics, reducing the 
patient, public health, and economic burdens of nosocomial infections, and 
mitigating the risk of antibiotic resistance. 
 
C.4.2 Potential Risks and Benefits 
C.4.2.1. Potential Risks 
There are risks associated with conducting this study, including loss of 
confidentiality; however, our group possess a unique set of resources and 

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may due to the pressure required to administer the enema. To mitigate 
the risk of a perforation, only gentle pressure will be used to administer the 
enema. All persons who administer the enema will be instructed to stop if 
the patient begins to have severe abdominal pain or cramping during the 
enema, which would be a sign of possible perforation. In this case, we 
would immediately send the subject to the emergency room for further 
evaluation, as bowel perforation is a surgical emergency. Hemorrhoid 
bleeding may also occur due to the modest pressure required to 
administer the enema. To mitigate the risk of bleeding, only gentle 
pressure will be used to administer the enema. All persons who administer 
the enema will be instructed to stop if the patient begins to bleed during 
the enema to prevent further blood loss. 
 
C.4.2.4. Baseline Geriatric Microbiome Risk 
Compositional changes in the gut microbiota are associated with aging.32 
Mariat and colleagues demonstrated that the ratio of Firmicutes to 
Bacteriodetes evolves throughout an individual’s lifetime, and that the elderly 
have a higher count of E. coli than the adult population.33 Furthermore, 
Claesson and colleagues established that geriatric residents of long-term care 
facilities have lower gut microbial diversity than elderly individuals who live in the 
broader community.32 Autologous FMT derived from an inadequately diverse 
baseline microbial community may fail to confer protective benefits against 
ARB. We intend to mitigate this risk by making eligibility criteria as permissive as 
possible, recognizing that physical frailty is associated with lower microbial 
biodiversity.32 Furthermore, although likely underpowered, we plan on 
conducting an a priori sub-group analysis of patients with high versus low 
microbial diversity to determine if there is a correlation between study outcomes 
and baseline diversity. 
 
C.4.2.5. Known Potential Benefits 
Studies have suggested that FMT may be able to decolonize patients colonized 
with ARB. Several case reports have reported de-colonization of ARB following 
FMT, including carbapenem-resistant Enterobacteraciae (CRE), extended 
spectrum beta-lactamase (ESBL)-producing Escherichia coli and methicillin-
resistant Staphylococcus aureus (MRSA) enteritis.20,21,22,23,24 Participants enrolled 
in this study who have received an FMT may benefit from close health 
surveillance at follow up consultations in comparison to non-participants. 
 
 

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C.5.2.3. Possible Exploratory Endpoints 
• 
Microbiome disruption indices (16S rRNA sequencing): MDI-community 
and MDI-species at baseline (pre-infection on the date of enrollment 
stool collection), post-antibiotics on the intervention/placebo date 
(Day 0, Day 3, Day 7, Day 28 and Month 6). MDI will be applied to pre- 
and post-intervention communities in comparison to baseline and 
reference communities. 
 
 
 
 

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C.7. Inclusion and Exclusion Criteria 
C.7.1. Inclusion Criteria 
C.7.1.1. Inclusion Criteria for Study Enrollment 
1. Long-term care residents associated with Boston University-Boston Medical 
Center nursing home consortium 
2. Adults (18 years or older)  
 
C.7.1.2. Inclusion Criteria for Randomization 
1. Infection requiring antimicrobial treatment at the discretion of the treating 
physician 
 
C.7.2. Exclusion Criteria 
C.7.2.1. Exclusion Criteria for Study Enrollment 
1. Pregnant. Participants of childbearing age will undergo urine pregnancy 
testing. 
2. Participant or substitute decision maker unable to provide informed 
consent  
3. Allergies to following ingredients generally recognized as safe: glycerol 
and sodium chloride 
4. Current enrollment in hospice 
5. Colostomy 
6. Unable to adhere to protocol requirements 
7. Any condition that the physician investigators deems unsafe, including 
other conditions or medications that the investigator determines puts the 
participant at greater risk from FMT 
8. Recent travel (last six months) to high risk regions based on the 
International SOS Medical Risk Rating system 
9. Recent exposure (last six months) to unsafe drinking water 
 
C.7.2.2. Exclusion Criteria for Stool Collection 
Enrollment stool sample will be tested for ARBs and processed into autologous 
FMT treatment (if of qualifying size). Sample will not be collected if any of the 
following are true: 
1. Oral or intravenous antibiotic exposure within previous 6 weeks of stool 
collection date (topical antibiotic will be permitted) 
2. Active gastrointestinal infection at stool collection 
3. Fever at the time of stool collection 
4. Currently ill or complaining of any of the following signs or symptoms of 
illness: fever, diarrhea, blood stools and/or vomiting 
5. Participants with a history of gastrointestinal (GI) illness within the past 30 
days prior to enrollment stool collection, that at the discretion of the site 

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investigator could reasonably be caused by one of the following 
pathogens 1) Vibrio spp. 2) Norovirus 3) Rotavirus 4) Adenovirus 5) Shiga 
toxin. 
 
C.7.2.3. Exclusion Criteria for Randomization  
• Colonized with CRE (assessed by PCR or culture assay during enrollment 
phase) 
• Colonized with VRE (assessed by PCR or culture assay during enrollment 
phase) 
• Colonized with ESBL (assessed by PCR or culture assay during enrollment 
phase) 
• Colonized with CDI (assessed by EIA assay on stool collected at 
enrollment phase) 
• Treatment with antibiotics that are active against MRSA (i.e. vancomycin 
or linezolid) prior to randomization to FMT intervention or placebo 
• Stool culture positive for common enteric pathogens (Salmonella spp., 
Shigella spp., Campylobacter spp.) 
o Participants who develop a GI illness with symptoms such as (but 
not limited to) vomiting or diarrhea within 30 days after collection of 
enrollment stool will be evaluated by the site investigator. If the site 
investigator determines that the symptoms were most likely caused 
by 1)Vibrio spp. 2) Norovirus, 3) Rotavirus, 4) Adenovirus, or 5) Shiga 
toxin, the enrollment stool will be sent out to test for these organisms. 
If the culture is positive for any of these organisms, the participant 
will be excluded from randomization 
• Any condition that the physician investigators deems unsafe, including 
other conditions or medications that the investigator determines puts the 
participant at greater risk from FMT 
• Participants who become severely immunocompromised, as defined by 
the investigator or treating physician, will be excluded prior to receiving 
intervention 
 
 
 

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C.8. Treatment Assignment Procedures 
C.8.1. Randomization Procedures 
Participants who fulfil the criteria for randomization (infection requiring antibiotic 
treatment), will be randomized on a 2:1 basis with a random permuted block 
sizes of 3 or 6 to receive FMT or placebo. Participant’s randomization will be 
carried out by the data coordination center chair using random number 
generation software to create a randomization schedule. 
 
The randomized, blinded treatment assignment will be sent via email to the site 
by the data coordination center chair after site confirmation that the 
participant has been treated with antibiotics and is eligible for randomization. 
This assignment will inform the site, in a blinded manner, about which treatment 
(active or placebo) the participant will be administered. 
 
C.8.2. Masking Procedure 
This is a randomized, double blind, placebo-controlled trial where both the 
participant and treating physicians will be blinded. Autologous fecal microbiota 
product (auto-FMP) enemas or placebo will be dispensed by Finch Therapeutics 
thereby maintaining blinding of study physicians and nurse practitioners. 
Placebo enemas will be packaged identical to auto-FMPs and consist of the 
same saline and glycerol buffer used in auto-FMP processing without the 
addition of stool. 
 
The data coordination center will maintain the randomization schedule and 
study participants and their health care proxies will remain blinded and not be 
provided any information until all participants have completed the trial and the 
database has been locked. 
 
Under normal circumstances, the blind should not be broken. The blind should 
be broken only if specific emergency treatment would be dictated by providing 
the treatment the participant was receiving. In such cases, the site PI must 
contact the Medical Monitor to request that the blind be broken. For 
participants who require unblinding, this information will be captured in the case 
report form (CRF). 
 
C.8.3. Interim Analysis 
An interim analysis will be performed by the unblinded study’s data coordination 
center chair after randomization of the first 10 participants. The purpose of this 
interim analysis is to assess safety and feasibility. 
 

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C.8.4. Participant Withdrawal 
A participant may choose to withdraw from this study at any time for any 
reason, without consequence. 
 
A participant may be withdrawn from the study by the site PI for any of the 
following reasons*: 
• Severe or intolerable adverse event  
• Lack of participant cooperation 
o Participants request to withdraw from study 
o Lack of compliance (fails to attend the follow-up visits as agreed) 
o Technical / logistical reasons (relocation) 
• Inclusion criterion not fulfilled 
• Other reasons (must be noted) 
 
*Treated participants should be followed in the study through their 6-month 
safety visit as long as feasible or as long as they are willing. 
 
C.8.5. Procedure for Handling Participant Withdrawal 
The primary reason for participant withdrawal should be noted on the 
‘participant withdrawal’ CRF. Participants will be encouraged to attend an Early 
Termination Visit where the final examination will be documented in the CRF. If 
possible, a final stool sample will be collected at this visit. 
 
Participants who are withdrawn from the study after randomization, but before 
intervention or placebo will be replaced. Possible reasons for participant 
withdrawal after randomization include but are not limited to: 
• Participants who are started on a new course of antibiotics after 
randomization and before intervention/placebo 
• Unrelated participant death 
 
Intention-to-treat analysis will be utilized according to best practices in clinical 
trials. 
 
C.8.6. Study Termination 
In the unlikely event that significant safety concerns arise, the PIs can terminate 
or halt the study pending review by the DSMB. In addition, this study may be 
halted early based on the DSMB charter or FDA recommendations. 

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C.9.4. Dosage, Preparation and Administration of Study Intervention 
C.9.4.1. Auto-FMP Enema 
The study physician/nurse practitioner will evaluate participants prior to 
administration of the enema specifically focusing on any contraindications for 
an enema. The study physician/nurse practitioner will ensure that participants 
are clinically well prior to enema administration. The auto-FMP enema will be 
thawed over the course of 1 hour in a warm water bath (approximately 30°C) or 
at room temperature for 4.5 hours. After thawing, the clinician will swirl 
moderately for 10 seconds to resuspend particulates and using a 50ml sterile 
disposable syringe the thawed material will be transferred into an enema 
administration bottle. The auto-FMP enema (up to 125ml) will be slowly 
administered rectally by retention enema, in keeping with standard of care, with 
a target dwell time of 1 hour if feasible. Participants will lie in the left lateral 
decubitus position but if mobility permits will rotate to supine and right lateral 
decubitus position. A 125ml enema will be administered using an enema 
‘squeeze’ bottle (similar to a sodium phosphate enema) but administration will 
be discontinued if there is any participant distress. 
 
C.9.5. Accountability Procedures for the Study Intervention/Investigational 
Product(s) 
The site PI (or designee) will maintain an accurate record of the receipt of the 
test materials, including the date received. The data coordination center chair 
or designee will maintain a log of all clinical trial materials (enema auto-FMP 
and placebo) dispensed. This clinical trial material accountability record will be 
available for inspection at any time. 
 
C.9.6. Assessment of Participant Compliance with Study 
Intervention/Investigational Product 
The retention enema will be administered by study staff and will be performed 
according to the enema administration SOP. 
 
C.9.7. Concomitant Medications/Treatments 
Given the patient population is elderly with multiple comorbidities, all 
medications will be accepted in this study at the discretion of the treating 
physician. This includes (but is not limited to): 
• Anti-hypertensives 
• Heart failure medications 
• Diuretics 
• Laxatives 
• Topical medications 
• Anti-depressants 

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• Statins 
• Diabetic medication 
• NSAID 
• Anti-neoplastics 
• Acid-blockers 
• Anticoagulants 
• Opioids 
• Iron supplementation 
 
Patients who receive antibiotics within the previous 6 weeks will be excluded 
from stool collection. 
 
C.9.8. Screening Visit and Patient Information (Visit 1) 
A diagrammatic representation of the study schedule can be found in C.19.1.  
 
All residents living in participating long-term care facilities will be equally eligible 
for enrollment into this study, provided they fulfill the eligibility criteria. Awareness 
about the study will be raised by standard, approved recruitment techniques. A 
detailed consent process will be administered by study staff who are trained in 
consenting procedures. 
 
Participants who agree to enroll in the study will complete the following: 
• Informed consent will be obtained from the participant. If the participant 
is judged to be cognitively impaired, consent will be obtained from their 
healthcare proxy/substitute decision maker. The purpose of the study, 
outcomes and its contribution to advancing healthcare in the elderly 
population will be explained. Each participant or substitute decision 
maker/proxy must provide written signed consent before proceeding with 
any study procedures. 
 
After informed consent is obtained, study staff will perform a detailed data 
collection via record review, which will include demographics, medical history, 
dietary information and current medications. Participants will also undergo a 
brief clinical assessment by a study physician/nurse practitioner. 
 
Data points to be collected: 
• Informed consent procedure 
• Verification of inclusion and exclusion criteria 
• General parameters: 
o Date of birth 
o Sex 

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o Smoking status 
o Race  
o Ethnicity 
• Past medical history and allergies  
o A focused collection of past medical history (list of common 
infectious and chronic inflammatory diseases) 
o Charlson Comorbidity Index 
• Current medication list 
• Dietary history will be collected using a structured institutional dietary 
record or similar tool 
• Social history 
o Alcohol, substance abuse, smoking history 
o Country of birth, duration living in the U.S. 
• Travel history 
• Family history  
• Level of mobility (ADL/IADL) and grip strength  
• Examination findings 
o Vital signs: temperature, height (measured or abstracted from 
medical records), weight (measured or abstracted from medical 
records), heart rate, blood pressure, O2 saturation, and waist 
circumference 
o Relevant review of systems 
o Overall assessment of current health 
 
C.9.9. Collection and Processing (Visit 2) 
At the collection and processing visit, study staff will collect stool and a rectal 
swab from participants. The stool and rectal swab will be labelled and 
transported within 12 hours to the laboratory and subsequently tested for CRE, 
VRE, ESBL, C. difficile and common enteric pathogens (Salmonella spp., Shigella 
spp., Campylobacter spp.). Ideally the swab will be collected at the same time 
as the stool sample. However, to encourage collection, the swab may also be 
collected up to 12 hours post stool collection, if the participant is willing. 
 
Only participants whose stool test negative for the above organisms will have 
their stool banked and processed into autologous enema. Any stool samples 
that test positive will be destroyed (although a research aliquot will be retained 
for future analysis and the site PI will be notified). 
 
C.9.10. Surveillance for Infectious Episodes 
Enrolled participants will undergo surveillance by study staff through bi-weekly 
review of patient medical records, review of facility logs or telephone/on-site/in-

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person ward rounds aimed at identifying participants who develop infections 
requiring antibiotics. The study data team will provide study site staff with a 
weekly updated log of participants who are eligible for randomization. 
• Study staff (nurse practitioners and physicians) based at the long-term 
care facilities will perform ongoing surveillance for development of new 
infections among study participants by monitoring nursing, hospital and 
long-term care facility logs. They will therefore be able to cross-reference 
all new infections with a list of study participants. 
 
C.9.11. Infectious Episode (Visit 3) 
Study staff will complete an infection CRF for each infection episode. This CRF 
will be used to track duration of the episode, dosage and duration of antibiotics. 
• Data points for infectious episode: 
o Date 
o Preliminary diagnosis 
o Antibiotic(s) 
 Name 
 Formulation (IV, suspension, capsules) 
 Dosage 
 Prescribed duration 
 Final (actual) duration of antibiotics 
 Change in antibiotics regime 
o Concomitant medication (Name, dose, route of administration, 
duration) 
o Hospital admission (yes/no) 
 Name of facility 
 Department where participant was admitted (ward / step 
down/ ICU) 
 Relevant medical procedures 
• Colonoscopy (including preparation) 
• Intestinal surgery 
• Dialysis 
• Other 
o Final diagnosis 
 
C.9.12. Post-Antibiotic Stool Collection (Visit 4) 
Once participants have completed their antibiotic course, the site PI or 
designee will be notified. Subsequently, a stool sample for microbial sequencing 
and ARB testing will be collected post-antibiotics, but prior to the FMT visit, which 
will occur after a minimum of 72 hours (+/- renal/hepatic adjustment at 
discretion of treating physician) after cessation of antibiotics. 

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If a stool sample is not available (for example due to constipation), then rectal 
swabs will be collected from the participant and processed, as per SOP, for 
microbiome sequence analysis and ARB testing. 
 
C.9.13. FMT Study Visit (Visit 5): Day 0 
At the FMT study visit, the participant will undergo a clinical examination by the 
study physician/nurse practitioner in order to confirm the participant is still 
eligible for randomization. Participants who become severely 
immunocompromised, as defined by the investigator/treating physician, will be 
excluded prior to receiving intervention. Once eligibility is confirmed, 
participants will receive their autologous FMT by auto-FMP enema or placebo 
enema. The FMT procedure will be conducted by the blinded study 
physician/nurse practitioner. Participants will be observed for 30 minutes 
following the FMT procedure. Participants and the nursing staff at the long-term 
care facility will be provided with information to assist with monitoring for 
adverse events. 
 
Data collection at FMT visit 
1. Confirm inclusion/exclusion criteria: each participant will be re-assessed 
for inclusion and exclusion criteria before administering treatment. 
• Interim medical history 
• The study physician/nurse practitioner will iterate through a list of 
common medical conditions in this patient population (See 
C.20).  
2. Prior and concomitant medications 
• The study physician/nurse practitioner will confirm that the 
patient has not received treatment with an antibiotic active 
against MRSA (i.e. vancomycin, linezolid) after collection of 
autologous fecal transplant material 
3. Clinical examination findings: 
• Vital signs: Temperature, heart rate, blood pressure, weight 
• Systemic examination 
• Overall health assessment 
• Safe to receive FMT (yes/no) 
• Immediate post FMT assessment 
• Adverse events (NIH criteria) 
 
C.9.13.1. Pre-FMT Procedure 
• A stool sample and rectal swabs will be collected just before the FMT 
administration for microbial sequencing and ARB testing, If a stool sample 

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is not available (for example due to constipation), then only the rectal 
swabs should be processed, as per SOP, for microbial sequencing and 
ARB testing 
• Study physician/nurse practitioner will perform a clinical assessment prior 
to FMT administration 
 
C.9.13.2. FMT Procedure 
• Participants undergo FMT delivery by retention enema delivery at the 
discretion of the treating physician. 
• Auto-FMP enemas (or placebo) will be administered according to the 
study’s SOP. 
 
C.9.13.3. Post- FMT Procedure 
• All participants will be observed for 30 minutes following the FMT 
procedure for immediate adverse reactions. Oral nutrition may 
commence immediately after enema administration. 
• Participants will be provided with information regarding monitoring for 
minor and severe adverse events related to the FMT procedure. 
Participants and their care team will be encouraged to report any 
concerning symptoms to staff at their long-term care facility. 
 
C.9.14 Follow-Up (Visit 6, 7, 8, 9) 
At the 3-day and 7-day post FMT visits, the study physician/nurse practitioner will 
perform a clinical assessment and administer a study questionnaire which will 
specifically inquire about solicited and unsolicited symptoms of AEs. Access to 
the medical records may be utilized to capture salient changes in healthcare 
status. Participants will have a stool sample and rectal swabs collected for 
microbial sequencing and ARB testing at their next available bowel movement 
within each follow-up window. If a stool sample is not available (for example 
due to constipation), then only the rectal swabs will be processed, as per SOP, 
for microbiome sequence analysis and ARB testing. 
 
At the 28-day and 6-month study visits, participants will undergo a similarly 
structured study visit which includes a clinical assessment, an AE focused 
questionnaire administration and collection of a stool sample and rectal swabs 
for ARB and 16S rRNA sequencing and analysis. 
 
C.9.14.1. Study Visit 6: Day 3 Post-FMT (+/- 1 Day) 
• Clinical assessment by study nurse/physician, specifically enquiring about 
adverse events related to the FMT 
• Data collection at visit: 

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o Interim medical history (See C.19.3) 
o Concomitant medication 
o Significant changes in diet 
o Changes in stool consistency (Bristol Stool Scale) and frequency 
o Clinical evaluation using standard, structured assessment 
o Vital signs: Temperature, heart rate, blood pressure, weight 
o General health status 
o Adverse events (NIH criteria) 
• Stool samples and rectal swabs will be collected for 16S sequencing and 
ARB testing. If a stool sample is not available (for example due to 
constipation), then only the rectal swabs will be processed, as per SOP, for 
microbiome sequence analysis and ARB testing 
 
C.9.14.2. Study Visit 7: Day 7 post-FMT (+/- 2 Day)- Primary End Point 
• Clinical assessment by study nurse / physician, specifically enquiring about 
adverse events related to the FMT. 
• Data collection at visit: 
o Interim medical history (See C.19.3) 
o Concomitant medication 
o Significant changes in diet 
o Changes in stool consistency (Bristol Stool Scale) and frequency 
o Clinical assessment findings 
o Vital signs: Temperature, heart rate, blood pressure, weight 
o General health status 
o Adverse events (NIH criteria) 
• Stool samples and rectal swabs will be collected for 16S sequencing and 
ARB testing. If a stool sample is not available (for example due to 
constipation), rectal swabs should be collected, as per SOP, from the 
participant for microbiome sequence analysis and ARB testing 
 
C.9.14.3. Study Visit 8: Day 28 (+/- 5 Day) - Intermediate Safety Assessment 
• Clinical assessment by study nurse/physician, specifically enquiring about 
adverse events related to the FMT 
• Data collection at visit: 
o Interim medical history (See C.19.3) 
o Concomitant medication 
o Significant changes in diet 
o Changes in stool consistency (Bristol Stool Scale) and 
frequency 
o Clinical assessment findings 
o Vital signs: Temperature, heart rate, blood pressure, weight  

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o General health status 
o Adverse events (NIH criteria) 
• Stool samples and rectal swabs will be collected for 16S sequencing and 
ARB testing. If a stool sample is not available (for example due to 
constipation), rectal swabs should be collected, as per SOP, from the 
participant for microbiome sequence analysis and ARB testing 
 
C.9.14.4. Study Visit 9: Month 6 (+/- 14 Day) - Long Term Safety Assessment 
• Telephonic interview by study nurse/doctor, specifically enquiring about 
adverse events related to the FMT 
• Data collection at visit: 
o Interim medical history (See C.19.3 ) 
o Concomitant medication 
o Significant changes in diet 
o Changes in stool consistency (Bristol Stool Scale) and frequency 
o Clinical assessment findings 
o Vital signs: Temperature, heart rate, blood pressure, weight 
o General health status 
o Adverse events (NIH criteria) 
• Stool samples and rectal swabs will be collected for 16S sequencing and 
ARB testing. If a stool sample is not available (for example due to 
constipation), rectal swabs should be collected, as per SOP, from the 
participant for microbiome sequence analysis and ARB testing 
 
C.9.15. Early Termination Visit 
If the participant terminates the study early, if feasible the study staff should 
perform an early termination study visit. Ideally, this will include an in-person 
clinical assessment, but if not feasible (i.e. participant leaves facility), the 
remaining data should be obtained from the medical record if available. 
 
Study staff will complete an ‘Early Termination CRF’ and the following clinical 
assessments: 
• Clinical assessment by study nurse/physician, specifically enquiring about 
adverse events related to the FMT 
• Data collection at visit: 
o Reason/s for withdrawing from study 
o Interim medical history (See C.19.3) 
o Concomitant medication 
o Significant changes in diet 
o Changes in stool consistency and frequency 
o Clinical assessment findings 

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o Vitals: Heart rate, blood pressure, temperature, weight 
o General health status 
o Adverse events (NIH criteria v 5.0) 
• If permitted by the participant, stool biobank stool samples and/or rectal 
swabs will be collected for 16s sequencing and ARB testing. If a stool 
sample is not available (for example due to constipation), rectal swabs 
should be collected, as per SOP, from the participant for microbiome 
sequence analysis and ARB testing 
 
C.9.16. Unscheduled Study Visit 
In the event that a participant develops an ARB associated infection or if 
believed to be in the participant’s best interest by the site PI, study staff will 
complete an ‘Unscheduled Study Visit CRF’ and the following clinical 
assessments: 
• Data collection at visit (if applicable): 
o Onset of infectious episode 
o Method of confirmation of ARB infection 
o Site from which organism was isolated 
o Prescribed antibiotics 
o Interim medical history (C.19.3) 
o Concomitant medication 
o Changes in stool consistency and frequency 
o Clinical assessment findings 
o Vitals: Heart rate, blood pressure, temperature, weight 
o Adverse events (NIH criteria) 
• Stool and/or rectal swab collection for 16S sequencing and ARB testing 
 
 

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C.10. Study Procedures / Evaluations 
C.10.1. Clinical Evaluation at Enrollment 
Enrollment: A comprehensive past medical history will be obtained from all 
participants. Study physician/nurse practitioner will conduct a clinical 
examination on all participants at enrollment and at FMT study visit (D0). 
 
C.10.2. Evaluation at Follow-Up Study Visits 
The study physician/nurse practitioner will conduct the clinical assessment at all 
follow-up study visits. 
 
Vital signs that will be recorded at each study visit include temperature, blood 
pressure and pulse rate measurement. Height and weight will be measured at 
enrollment if feasible for the patient; otherwise this will be abstracted from the 
medical record.  
 
Study physician/nurse practitioner will enquire about adverse events at each 
study visit following the FMT (i.e. starting at visit 6). All adverse events including 
solicited and unsolicited, minor and severe adverse events will be recorded at 
each study visit beginning with study visit number 6. All adverse events will be 
recorded on the study’s adverse event CRF and all serious adverse events will 
be recorded on the study’s serious adverse event form and must be reported to 
the sponsor within 24 hours of knowledge of the event. 
 
C.10.3. Evaluation of Safety Outcome 
All adverse events both unrelated and related to the FMT procedure will be 
recorded during the course of this study. The primary outcome of this study is to 
evaluate the safety (short-term) of FMT in this study population at day 7 that is 
defined as the absence of NIH Grade ≥2 adverse events. This primary outcome 
will be evaluated using the study adverse event CRFs. 
 
C.10.4. Laboratory Evaluations 
C.10.4.1. Enrollment 
Stool samples and rectal swabs should be collected from all participants. 
 
C.10.4.2. Screening Only Samples 
Samples greater than 10g but less than 40g will be screened for CRE, VRE , ESBL, 
C. difficile and common enteric pathogens (Salmonella spp., Shigella spp., 
Campylobacter spp.), but will NOT be processed into enema.  
 

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C.10.4.3. Samples Processed into Enemas 
Stool samples meeting a minimum enema processing weight threshold of 40 
grams will be tested for CRE, VRE, ESBL, C. difficile and common enteric 
pathogens (Salmonella spp., Shigella spp., Campylobacter spp.), using either a 
PCR test or culture-based assay. These stool samples will then be processed into 
an auto-FMP enema. The participants who test positive for ARB at this stage will 
be excluded from the randomization portion of the study. A portion of stool from 
all participants will be aliquoted into 4 equal aliquots and stored at -80°C for 
future DNA extraction and 16S rRNA sequencing. Stool will be homogenized 
 
and filtered 
. 
 
C.10.4.4. Study Visit Stool Collection 
Stool from each study visit will be collected for biobanking, ARB testing and 
planned future calculation of the microbial disruption index (MDI). 
 
C.10.4.5. Rectal Swabs 
Rectal swabs should be collected pre-FMT and at all post-FMT study visits (visits 4 
through 9) for 16S rRNA sequencing and ARB testing. All swabs will be processed 
according to the sample collection SOP. 
a. MRDO testing: Swabs that are collected for MDRO testing will be sent 
 at room temperature within 2 days of collection. 
b. CDI testing: Swabs that are collected for CDI (PCR) testing will be sent 
 on dry ice. 
c. 16S rRNA sequencing: Swabs for 16s rRNA sequencing will be stored in 
in -80˚C freezer for biobanking purposes. 
 
 
C.10.5. Specimen Handling and Shipping 
All patients will be assigned a unique barcode number/participant ID. Each floor 
in a long-term care facility has a dedicated nurse manager and team of 
certified nurse assistants (CNA), who will be informed about the study and the 
participants who are enrolled into the study. Study staff will collect the stool and 
rectal swabs at the bedside and label the specimens. All specimens and swabs 
will be treated under strict infection control procedures, which include gloves to 
be worn at all times when handling samples and strict hand sanitizing before 
and after handling specimens. The labeled stool and rectal swab specimens will 
then be packaged and transported. 
 
Courier services will be utilized to transport specimens on the day of collection. 
Specimens will be closely tracked during transportation using the labeling and 
log books. Formal hand-overs with recording of specimen labels in tracking 

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logbooks will be required during the transport of specimens (i.e. study staff 
handover to courier service, courier service handover to laboratory staff). 
 
Stool to be used for the autologous FMT will be processed under aseptic 
conditions in the laboratory into an auto-FMP enema and stored in a -80°C 
freezer. Once a participant has been identified as requiring a course of 
antibiotics for an infection, their auto-FMP enema will be dispatched to the 
study site. Specific laboratory software will be used to track location of all 
collected specimen at all times. 
 
Once an FMT date has been scheduled, the enema treatment for that patient 
will be dispensed by the study staff. A ‘double check system’ will be employed 
when dispensing auto-FMP product from freezer storage and before 
administration of auto-FMP product to recipients. Two staff members (duplicate) 
are required to check that the specimen barcode matches the donor study 
identification. 
 

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C.11. Assessment of Safety 
Safety will be assessed by the frequency and severity of adverse events (AE). For 
additional information, see Section C18 ‘Safety Reporting and Definitions’. 
 
C.11.1. Definition of Adverse Events (AE) 
Adverse events (AEs) will be recorded at each regular scheduled study visit 
starting with the FMT visit (visit number 5) in the study patient record (source 
document) as well as on a specific AE case report form (CRF). 
 
An AE is any untoward medical occurrence in a study patient or clinical 
investigation participant who is administered a pharmaceutical product. An AE 
does not necessarily have a causal relationship with this treatment. An AE can 
therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease temporally associated with the use of a 
medicinal product, whether or not related to the medicinal product, e.g.: 
• Any new clinical diagnosis 
• Any symptom that requires medical clarification or leads to in-patient 
admission (surgery or accident) 
• Any suspected adverse drug reaction (ADR) 
• Any symptom that appears on the study patient’s medical records 
• Any event related in time with the application of the study medication 
and affecting the health of the study patient (including laboratory value 
changes) 
 
If there is any doubt as to whether a clinical observation is an AE, the event 
should be reported. AEs must be graded for severity and relationship to study 
product. 
 
C.11.2. NIH Grading of Severity of the Event 
AEs will be assessed by the clinician using the NIH Common Terminology Criteria 
for Adverse Events (CTCAE) defined grading system version 5.0 (see C.18.2). 
Briefly, the criteria for estimating adverse event severity grade: 
• Grade 1, Mild: Asymptomatic or mild symptoms; clinical or diagnostic 
observations only; intervention not indicated 
• Grade 2, Moderate: Minimal, local or noninvasive intervention 
indicated; limiting age-appropriate instrumental activities of daily living 
(ADL) 
• Grade 3, Severe: Severe or medically significant but not immediately 
life-threatening; hospitalization or prolongation of hospitalization 
indicated; disabling; limiting self-care ADL 

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• Grade 4, Life threatening: Places the patient or subject at immediate 
risk of death. It does not include an adverse event that, had it 
occurred in a more severe form, might have caused death 
• Grade 5, Death 
 
C.11.3. Relatedness 
All adverse events, regardless of relatedness should be reported. All adverse 
events should be evaluated for relatedness when reporting and documenting 
on the CRF. 
 
The following guidelines of relatedness are used, modified from the NIH 
guidelines: 
• Related: The adverse event is related to the FMT material – i.e. an 
event that follows a reasonable temporal sequence from 
administration of the FMT material, and that could not be reasonably 
explained by the known characteristics of the patient’s clinical state. 
• Not Related: The adverse event is not related to the FMT material. – i.e. 
another cause of the event is most plausible; and/or a clinically 
plausible temporal sequence is inconsistent with the onset of the event 
and the study intervention and/or a causal relationship is considered 
biologically implausible. 
 
C.11.4. Solicited Adverse Events After Auto-FMP 
In addition to open-ended questions on adverse events meeting the above 
definitions, specific potential adverse events will be inquired about during the 
follow up period (following FMT through to 6 months after FMT): 
Symptoms 
clinically more 
severe than at 
participant’s 
baseline 
Severity 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Grade 5 
Fever 
38.0 - 39.0 
degrees C 
(100.4 - 102.2 
degrees F) 
>39.0 - 40.0 
degrees C 
(102.3 - 104.0 
degrees F) 
>40.0 degrees 
C (>104.0 
degrees F) for 
<=24 hrs 
>40.0 degrees 
C (>104.0 
degrees F) for 
>24 hrs 
Death 
Diarrhea 
Increase of 
<4 stools per 
day over 
baseline pre-
FMT; mild 
increase in 
ostomy 
Increase of 4 
- 6 stools per 
day over 
baseline; 
moderate 
increase in 
ostomy 
Increase of 
>=7 stools per 
day over 
baseline; 
incontinence; 
hospitalization 
indicated; 
Life-
threatening 
consequence
s; urgent 
intervention 
indicated 
Death 

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C.11.5. Serious Adverse Events 
An adverse event or suspected adverse reaction is considered “serious” if, in the 
view of the PIs, it results in any of the following outcomes: 
• Death 
• Life-threatening adverse event* 
• Inpatient hospitalization or prolongation of existing hospitalization 
• A congenital anomaly/birth defect 
• Persistent or significant disability or incapacity or substantial disruption 
of the ability to conduct normal life function 
• Important medical events that may not result in death, be life-
threatening, or require hospitalization may be considered serious when, 
output 
compared to 
baseline 
output 
compared to 
baseline; 
limiting 
instrumental 
ADL 
severe 
increase in 
ostomy output 
compared to 
baseline; 
limiting self-
care ADL 
Vomiting 
1 - 2 episodes 
(separated 
by 5 minutes) 
in 24 hrs 
3 - 5 
episodes 
(separated 
by 5 minutes) 
in 24 hrs 
>=6 episodes 
(separated by 
5 minutes) in 
24 hrs; tube 
feeding, TPN 
or 
hospitalization 
indicated 
Life-
threatening 
consequence
s; urgent 
intervention 
indicated 
Death 
Abdominal pain 
Mild pain 
 
Moderate 
pain; limiting 
instrumental 
activities of 
daily living 
Severe pain; 
limiting self-
care activities 
of daily living 
n/a 
n/a 
Constipation 
Occasional 
or 
intermittent 
symptoms; 
occasional 
use of stool 
softeners, 
laxatives, 
dietary 
modification, 
or enema 
Persistent 
symptoms 
with regular 
use of 
laxatives or 
enemas; 
limited 
instrumental 
activities of 
daily living 
Obstipation 
with manual 
evacuation 
indicated; 
limiting self-
care activities 
of daily living 
 
Life-
threatening 
consequence
s; urgent 
intervention 
indicated 
Death 
Bloating 
Mild 
symptoms; 
intervention 
not indicated 
Moderate; 
persistent; 
psychosocial 
sequelae 
n/a 
n/a 
n/a 

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based upon appropriate medical judgment, they may jeopardize the 
patient or subject and may require medical or surgical intervention to 
prevent one of the outcomes listed in this definition. 
 
*Life-threatening adverse event. An adverse event is considered “life-threatening” if, in the view 
of the PIs, it places the patient or participant at immediate risk of death. It does not include an 
adverse event which, had it occurred in a more severe form, might have caused death. 
 
Any adverse event or suspected adverse reaction that meets the criteria for 
serious adverse event will be (regardless of relatedness): 
• Reported to the sponsor within 24 hours of knowledge of the event 
• Recorded on the appropriate SAE CRF. In the event the eCRF system is 
unavailable, the site will notify the sponsor using an alternative means 
of encrypted communication and record the information in the CRFs 
once the system is back online 
• Followed through resolution by a study clinician 
• Reviewed and evaluated by a study clinician 
 
C.11.6. Unsolicited Adverse Events 
Upon enrollment in the study, the study patients will be instructed to contact the 
site PI if an AE occurs. These unsolicited, unrelated non-serious adverse events 
occurring from the time of FMT until 6 months following FMT. 
 
C.11.7. Reporting of Adverse Events 
Study participants will be instructed to contact the study nurse or physician if 
any serious or unexpected adverse event occurs. Study staff will enquire about 
AEs at each study visit. Reported AE’s will be recorded in detail in an AE CRF. 
 
AE information to be collected in the AE CRF: 
• Nature of the event (diagnosis) 
• Date of onset 
• Concomitant treatment: product (generic name), indication, dosage, 
dosage interval, presentation, mode of administration, administration 
regimen – this information is captured in a separate concomitant 
medication log that is linked to the AE 
• Duration of the AE 
• Severity 
• Seriousness 
• Causality or relatedness 
• Action taken with study drug 
• Outcome 
 

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The course and outcome of the adverse event will be noted as follows: 
• Recovered without sequelae 
• Not yet recovered 
• Recovered with sequelae 
• Fatal 
 
Any SAE (including death, irrespective of the cause) occurring during the study 
will be immediately reviewed by the site PI, i.e. within 24 hours and reported to 
the Sponsor. 
 
A specific SAE CRF will be provided similar to C.18.2. The report must contain a 
detailed description of the symptoms observed and the concomitant treatment 
administered. Furthermore, the report must comment on a possible causative 
relationship between the AE and the trial medication. Each SAE must be 
followed until it is resolved or can be explained satisfactorily, or until the end of 
the 6-month follow-up period, whichever comes first (unless additional follow-up 
is specifically requested by the medical safety monitor or the DSMB). 
 
If determined to be a SUSAR (suspected unexpected serious adverse reaction – 
SUSAR; C.18.2 and C.18.3) by the site PI, study medical monitor or lead PI, the 
event will be reviewed by the DSMB. Regulatory filing to the FDA or local IRB as 
per standard practices will occur. 
 
The DSMB will review all SAEs every 6 months or ad hoc depending on the 
clinical case at the discretion of the site PI, study medical monitor and lead PI. 
 
For non-serious adverse reactions (related or not related) the site PI will 
complete a report and submit it to the medical monitor and lead PI. All non-
serious adverse reactions will be reviewed by the DSMB every 6 months or ad 
hoc depending on the clinical case at the discretion of the site PI, study medical 
monitor and lead PI. 
 
In accordance with safety requirements, the PIs will inform the IRB of the study at 
the Boston University-Boston Medical Center and will make sure that the 
involved persons will obtain adequate information. The following instructions 
must be heeded: 
• In the case of an intolerable SAE, the study patient must, at the decision of 
the site PI, be withdrawn from further treatment/placebo, and 
symptomatic treatment must be administered. The participant may opt to 
voluntarily provide sample for duration of study 
• The measures taken must be recorded on the CRF 

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• In accordance with local legislation, the site PI will submit copies of the 
final SAE-report to their local IRB, if necessary 
• The site PI will submit a copy of the final SAE-report to the Sponsor 
 
C.11.8. Follow-up of Participants After Adverse Events 
AEs will be followed until resolution or until the 6-month follow-up visit, whichever 
occurs first. Resolution of an AE is defined as the return to pretreatment status or 
stabilization of the condition with the expectation that it will remain chronic. 
 
Follow-up procedures, evaluations, and outcomes will be recorded on the 
participant's CRF. 
 
C.11.9. Halting Rules 
C.11.9.1. Study Halting Rules 
Enrollment and administration of study intervention will be suspended pending a 
safety review by the DSMB to determine whether the study will be terminated or 
re-initiated in the following situations: 
• Three or more of the randomized participants in a study treatment group 
have a Grade 3 AE of the same organ system deemed related to the 
study intervention. 
• Any serious adverse event of an enrolled participant related to the study 
intervention. 
• An overall pattern of symptomatic, clinical, or laboratory events that the 
Medical Monitor considers related to study product and that may appear 
minor in terms of individual events, but that may collectively represent a 
serious potential concern for safety. 
 
CBER will be notified of any study halt that occurs as a result of any of the above 
halting criteria. 
 
C.11.9.2. Individual’s Halting Rules 
Participants who meet any of the following criteria must be assessed by the PIs 
to determine if it is in the participant’s best interest to stop the study product(s): 
• Participant choice (Withdrawal of consent) 
• Participant’s non-compliance 
• Development of a significant medical condition and/or participation in 
the study is no longer in the best interest of the participant 
 

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C.11.10. Safety Oversight 
C.11.10.1 Data and Safety Monitoring Board (DSMB) 
Safety oversight will be under the direction of a DSMB. The DSMB is an 
independent group of experts who will advise the study PIs. The primary 
responsibilities of the DSMB are to 1) periodically review and evaluate the 
accumulated study data for participant safety, study conduct and progress, 
and when appropriate, efficacy, and 2) make recommendations to the 
continuation, modification or termination of the trial. The DSMB will be 
composed of at least 3 voting members. The membership will include a 
chairperson who has prior DSMB experience. One member will be an 
experienced gastroenterologist and one member will be an experienced 
geriatric specialist. All DSMB members will be separate and independent of 
study personnel participating in this trial and should not have scientific, financial 
or other conflict of interest related to the trial. Procedures for DSMB data reviews 
will be defined in the DSMB Charter that will include DSMB membership, 
responsibilities, and the scope and frequency of data reviews. The DSMB will 
have access to unblinded treatment assignments during the closed session of 
their meetings. The study should be reviewed by the DSMB at least bi-annually. 
The DSMB may conduct a safety interim analysis after 50% of patients have 
enrolled in the treatment arm. 
 
 

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C.12. Clinical Monitoring 
C.12.1. Site Monitoring Plan 
Site monitoring is conducted to ensure that the human participant protection, 
study and laboratory procedures, study intervention administration, and data 
collection processes are of high quality. The lead PI (or delegate) will conduct a 
site-monitoring visit(s) as detailed in a monitoring plan. The PIs will permit 
authorized representatives 
, regulatory agency and/or an auditing body 
to inspect facilities and records relevant to this study, if needed. 
 
Monitoring visits will include, but are not limited to, review of regulatory files, 
accountability records, eCRFs, informed consent forms, medical and laboratory 
reports, and protocol compliance. Study monitors will meet with site PIs to 
discuss any problems and actions to be taken and document visit findings and 
discussions. 
 
 

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C.13. Statistical Considerations 
This is a pilot, randomized double blinded placebo controlled clinical trial to 
determine the safety and efficacy of autologous FMT on the intestinal 
microbiome and the prevention of ABR colonization and infection. 
 
C.13.1. Study Objectives 
To investigate the safety and the role of autologous fecal microbiota 
transplantation (FMT) for the prevention of antibiotic resistant infections through 
microbiome restoration. 
 
C.13.2. Primary Endpoint of Short-Term Safety  
Proportion of participants with AEs (NIH Grade ≥2) at Day 7 following autologous 
FMT. 
 
C.13.3. Secondary Endpoints 
C.13.3.1. Clearance of ARB among Patients Co-colonized at Day 3, Day 7, Day 
28 and Month 6 
Proportion of co-colonized participants who clear the ARB following autologous 
FMT. 
 
C.13.3.2. Proportion of Participants Who Develop ARB Associated Infections at 
Day 3, Day 7, Day 28, and Month 6  
Proportion of participants who develop ARB associated infections following 
autologous FMT. 
 
C.13.3.3. Proportion of Participants Who Develop AE’s by Day 28  
Proportion of participants who develop AE’s by Day 28 following autologous 
FMT. 
 
C.13.4. Possible Exploratory Endpoint 
C.13.4.1. Microbiome Disruption Indices (16S rRNA sequencing) 
Description of severity of microbial community disruption following antibiotic 
administration. Microbiome disruption indices (MDI) will be developed by Finch 
Therapeutics, using 16S rRNA sequence data from samples collected pre- and 
post-FMT. We will assess the suitability of two measures of disruption, applied to 
pre- and post-intervention communities in comparison to baseline and 
reference communities, and determine which of these metrics best correlates 
with clinical outcomes. These measures will comprise: 1) MDI-community which 
assesses community-level divergence, as measured by the Jensen-Shannon 
divergence from a reference; and 2) MDI-species, which assesses species-level 
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the baseline (or reference) community lost due to disruption (i.e. the percent of 
the reference community that is represented by OTUs missing in the disrupted 
community). The reference data set will consist of a metacommunity that we will 
build using healthy OpenBiome donors. MDI will be assessed as the deviation 
from the healthy metacommunity. 
 
C.13.5. Sample Size 
As this is a pilot proof-of-concept study, no formal power calculation is possible 
and a sample size of convenience was utilized (n=20). In order to yield the 
target sample size, a total of 180 participants is predicted to be required 
assuming: 
1. 40% exclusion for positive ARB in stool per Trick and colleagues study3 
2. 35% of residents will develop an infection requiring antibiotics annually 
based on direct historical observations at these sites (C.19.2) 
3. Adjusted for 7.5-month treatment window to meet target study period 
(C.19.3) 
4. An anticipated drop-out rate of 15% 
 
Given that the 4 nursing homes participating in the study house a total of 866 
residents, the total enrollment of 180 participants can be achieved with a 20.8% 
enrollment rate. The sites feel this is realistic given that most participants will only 
need to undergo informed consent and provide a stool sample for processing 
and testing. See C.19.2 for a schematic of this process. 
 
C.13.6. Final Analysis Plan 
Categorical data will be described using descriptive statistics (proportions and 
percentages). Continuous data will be described using means and standard 
deviations (normally distributed data) or using medians and interquartile range 
(non-parametric data). Appropriate comparative statistical tests will be chosen 
based in the variable types (categorical, dichotomous, continuous) and 
distribution (parametric, non-parametric) and will be used to describe significant 
differences between intervention and control groups. Where appropriate, point 
estimates and confidence intervals will be reported. The p-value will be two 
tailed with a significance level of 0.05. 
 
For the primary outcome of AEs at day 7, the proportion of AEs occurring in the 
intervention group will be compared to the proportion of AEs occurring in the 
control group at day 7, using the Z-score test for two populations with 95% 
confidence intervals. Given the limited sample size, the confidence intervals will 
likely be quite wide. The p-value will be two tailed with a significance level of 
0.05. 

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For the secondary outcome of ARB colonization at days 3, 7, and 28, the 
proportion of ARB colonizations occurring in the intervention group will be 
compared to the proportion of ARB infections occurring in the control group at 
each time point, using the Z-score test for two populations with 95% confidence 
intervals. Given the limited sample size, the confidence intervals will likely be 
quite wide. The p-value will be two tailed with a significance level of 0.05.  
 
 

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C.14. Source Documents and Access to Source Data/Documents 
Each participating site will maintain appropriate medical and research records 
for this trial, in compliance with ICH E6 GCP, Section 4.9, and regulatory and 
institutional requirements for the protection of confidentiality of participants. 
Forms for use as source documents will be derived from the electronic CRFs. 
Additional source data include records of clinical findings, observations, or other 
activities in a clinical trial necessary for the reconstruction and evaluation of the 
trial. Examples of these documents and data records include, but are not limited 
to, hospital records, clinical and office charts, laboratory notes, memoranda, 
pharmacy dispensing records, recorded data from automated instruments, 
copies or transcriptions certified after verification as being accurate and 
complete, microfiches, photographic negatives, microfilm or magnetic media, 
imaging, and participant files and records kept at the pharmacy, laboratories, 
and medico-technical departments involved in the clinical trial. 
 
 
 

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C.15. Quality Control and Quality Assurance 
The site PI or delegate is responsible for conducting routine quality assurance 
(QA) and quality control (QC) activities to internally monitor study progress and 
protocol compliance. The site PI will provide direct access to all trial-related sites, 
source data/documents, and reports for the purpose of monitoring and 
auditing, and inspection by local and regulatory authorities. The site PI will 
ensure all study personnel are appropriately trained and applicable 
documentations are maintained on site. 
 
The site PI will verify that the clinical trial is conducted and data are generated, 
documented (recorded), and reported in compliance with the protocol, GCP, 
and the applicable regulatory requirements. 
 
C.15.1. Procedural Quality Control 
Data coordination center chair in conjunction with site PIs will implement quality 
control procedures including a ‘double-check’ procedures when 
collecting/labeling stool and rectal swab specimens and administering FMTs at 
study sites. 
 
Study personnel will be required to verify that specimens have been labelled 
appropriately at collection. Similar, stringent tracking and labelling processes will 
be implemented while stool specimens are being processed. Two study 
personnel will be required to verify identification of the participant during the 
administration of fecal microbiota to recipients, thereby ensuring that the 
recipient receives their own donated stool during the FMT. 
 
C.15.2. Database Quality Control 
QC procedures regarding data entry will be implemented. Regular data quality 
control checks will be run on the database. Any missing data or data anomalies 
will be communicated to the site(s) for clarification and resolution. 
 
 

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C.16. Ethics/Protection of Human Participants 
C.16.1. Ethical Standard 
The PIs will ensure that this study is conducted in full conformity with principles of 
the Belmont Report: Ethical Principles and Guidelines for the Protection of 
Human Subjects of Research of the National Commission for the Protection of 
Human Subjects of Biomedical and Behavioral Research (April 18, 1979) and 
codified in 45 CFR 46, 21 CFR 50 and 56, and ICH E6; 62 Federal Regulations 
25691 (1997), if applicable. 
 
C.16.2. Institutional Review Board 
Each participating institution will provide for the review and approval of this 
protocol and the associated informed consent documents, by an appropriate 
ethics review committee or IRB. Any amendments to the protocol or consent 
materials must also be approved before they are placed into use unless change 
is for the safety of the participant. Only those IRB members who are 
independent of the PIs should provide an opinion on study related matters. 
Verification of IRB approval of the protocol and the written informed consent will 
be transmitted by the PIs or designee prior to the shipment of clinical trial 
material. No deviations from or changes to the protocol will be initiated without 
prior approval of an appropriate amendment unless change is for the safety of 
the participant. Each participating institution is responsible for ensuring 
Continuing Review at least once a year and for keeping the IRB apprised of the 
progress of the study and any changes to the protocol. 
 
C.16.3. Informed Consent Process 
The written consent document will embody the elements of informed consent as 
described in the Declaration of Helsinki and will adhere to the ICH Harmonised 
Tripartite Guideline for Good Clinical Practice. Informed consent should be 
implemented before any protocol-specified procedures or interventions are 
carried out. Informed consent will be obtained in accordance with 21 CFR 50.25 
and 45 CFR 46. Information should be presented both orally and in written form. 
A site PI or designee will describe the protocol to potential participants and/or 
substitute decision maker/proxy guardian face-to-face, over the phone, and/or 
by email. The Participant Information and Consent Form may be read to the 
participants, but in any event, the site PI shall give the participants ample 
opportunity to inquire about details of the study and ask any questions before 
the signing and dating the consent form. 
 
Study staff must inform participants and/or substitute decision maker/proxy that 
the trial involves research, and explain the purpose of the trial, those aspects of 
the trial that are experimental, any expected benefits, all possible risks (including 

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a statement that the particular treatment or procedure may involve risks to the 
participant or to the embryo or fetus, if the participant is or may fathers a child, 
that are currently unforeseeable), the expected duration of the participant’s 
participation in the trial, the procedures of the research study, including all 
invasive procedures, and the probability for random assignment to treatment 
groups. Participants and/or substitute decision maker/proxy will be informed that 
they will be notified in a timely manner if information becomes available that 
may be relevant to their willingness to continue participation in the trial. They 
must also be informed of alternative procedures that may be available, and the 
important potential benefits and risks of these available alternative procedures. 
Participants and/or legal guardian must receive an explanation as to whether 
any compensation and any medical treatments are available if injury occurs, 
and, if so, what they consist of, or where further information may be obtained. 
Participants and/or substitute decision maker/proxy guardian must be informed 
of the anticipated financial expenses, if any, to the participant for participating 
in the trial, as well as any anticipated prorated payments, if any, to the 
participant for participating in the trial. They must be informed of whom to 
contact (e.g., the PI or study physician/nurse practitioner) for answers to any 
questions relating to the research project. Information will also include the 
foreseeable circumstances and/or reasons under which the participant’s 
participation in the trial may be terminated. The participants and/or substitute 
decision maker/proxy must be informed that participation is voluntary and that 
they are free to withdraw from the study for any reason at any time without 
penalty or loss of benefits to which the participant is otherwise entitled. 
 
Neither the site PI nor the trial staff should coerce or unduly influence a 
participant to participate or continue to participate in the trial. The extent of the 
confidentiality of the participants’ records must be defined, and participants 
must be informed that applicable data protection legislation will be followed. 
Participants and/or substitute decision maker/proxy must be informed that the 
monitor(s), auditors(s), IRB and regulatory authority(ies) will be granted direct 
access to the participant’s medical records for verification of clinical trial 
procedures and/or data without violating the confidentiality of the participant, 
to the extent permitted by the applicable laws and regulations, and that, by 
signing a written informed consent form, the participant is authorizing such 
access. Participants and/or substitute decision maker/proxy must be informed 
that records identifying the participant will be kept confidential, and, to the 
extent permitted by the applicable laws and/or regulations, will not be made 
publicly available and, if the results of the trial are published, the participant’s 
identity will remain confidential. 
 

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Consent forms must be in a language fully comprehensible to the prospective 
participants. Informed consent shall be documented by the use of a written 
consent form approved by the IRB and signed and dated by the participant or 
substitute decision maker/proxy and the person who conducted the informed 
consent discussion. The signature confirms that the consent is based on 
information that has been provided and all questions have been answered to 
the prospective participant’s satisfaction. Each participant’s signed informed 
consent form must be kept on file by the PIs for possible inspection by Regulatory 
Authorities and/or the Sponsor and Regulatory Compliance persons. The 
participant should receive a copy of the signed and dated written informed 
consent form and any other written information provided to the participants 
and should receive copies of any signed and dated consent form updates and 
any amendments to the written information provided to participants. 
 
C.16.4. Exclusion of Women, Minorities, and Children (Special Populations) 
Children and pregnant women are excluded for safety reasons. 
 
C.16.5. Participant Confidentiality 
Participant confidentiality is held strictly in trust by the site PIs and their 
designees. This confidentiality is extended to cover testing of biological samples 
in addition to the clinical information relating to participating participants. 
 
The study protocol, documentation, data, and all other information generated 
will be held in strict confidence. No information concerning the study or the 
data will be released to any unauthorized third party without prior written 
approval from the Sponsor. 
 
The study monitor or other authorized representatives of the PIs and FDA may 
inspect all documents and records required to be maintained by the site PI, 
including, but not limited to, medical records (office, clinic, or hospital) and 
pharmacy records for the participants in this study. The clinical study site will 
permit access to such records. 
 
C.16.6. Study Discontinuation 
The Sponsor has the right to terminate this study or an individual site’s 
participation at any time. Reasons for terminating the study may include, but 
are not limited to, the following: 
• Incidence or severity of adverse events indicates a potential health 
hazard 
• Data recording is inaccurate or incomplete 

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• Site PI does not adhere to the protocol or applicable regulatory guidelines 
in conducting the study 
 
C.16.7. Future Use of Stored Specimens 
Any leftover specimens will be stored and may be used for future research. 
These specimens will be stored indefinitely after the study is completed. In the 
informed consent document, participants will be given an opportunity to 
choose whether or not their de-identified barcoded specimens are stored for 
future use. For participants who choose not to allow storage of their samples for 
future use, their samples will be destroyed at the end of the study. 
 
There are no benefits to participants in the collection, storage and subsequent 
research use of specimens. Reports about future research done with 
participant’s samples will NOT be kept in their health records, but participant’s 
samples may be kept with the study records or in other secure areas. 
Participants can decide if they want their samples to be used for future research 
or have their samples destroyed at the end of the study. A participant’s decision 
can be changed at any time before the end of the study by notifying the study 
doctors or nurses in writing. However, if a participant consents to future use and 
some of their stool has already been used for research purposes, the information 
from that research may still be used. 
 
Samples may be shared with other investigators at other institutions with the 
consent of the lead PI. Each sample will be encoded (labeled) only with a 
barcode and a unique tracking number to protect participant’s confidentiality. 
 
Research using stored specimens may be conducted by other institutions. Any 
specimens and data provided to the receiving-institution will be coded. 
Unequivocally, neither individual personal identifiers nor the key linking coded 
data to individuals will be released to the receiving-institution. The use of any of 
these specimens for any future studies will only be performed after the lead PI 
has authorized the use of these specimens. 
 
C.16.8. Data Management Responsibilities 
All source documents and laboratory reports must be reviewed by the clinical 
team and data entry staff, who will ensure that they are accurate and 
complete. Adverse Events must be graded, assessed for severity and causality, 
and reviewed by the site PI or designee and reported to the sponsor. 
 

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Data collection is the responsibility of the clinical trial staff at the site under the 
supervision of the site PI. During the study, the site PI must maintain complete 
and accurate documentation for the study. 
 
C.16.9. Data Capture Methods 
Clinical data (including AEs, concomitant medications, and solicited events 
data) and clinical laboratory data will be entered into a 21CFR11-compliant 
Internet Data Entry System, REDCap. The data system includes password 
protection and internal quality checks, such as automatic range checks, to 
identify data that appear inconsistent, incomplete, or inaccurate. Clinical data 
will be entered directly from the source documents. 
 
C.16.10. Types of Data 
Data for this study will include clinical, safety and microbiological outcome 
measures. 
 
C.16.11. Timing/Reports 
Interim reports for the DSMB will be prepared when approximately 50% of 
treating participants complete enrollment and every 6 months. Interim statistical 
reports may be generated as deemed necessary and appropriate by the lead 
PI. Other safety summary reports may be generated for the DSMB. A final report 
will be prepared following the availability of all the clinical, safety and efficacy 
data. 
 
C.16.12. Study Records Retention 
Study files (except for future use consent forms) must be maintained for a 
minimum of two years after the last approval of a marketing application in an 
ICH region and until there are no pending or contemplated marketing 
applications in and ICH region or at least 2 years have elapsed since the formal 
discontinuation of clinical development of the investigational product. These 
documents should be retained for a longer period, however, if required by local 
regulations. No records will be destroyed without the written consent of the lead 
PI, if applicable. It is the responsibility of the lead PI to inform the site PI when 
these documents no longer need to be retained. Consent forms for future use 
will be maintained as long as the sample exists. 
 
C.16.13. Protocol Deviations 
A protocol deviation is any noncompliance with the clinical trial protocol, GCP, 
or protocol-specific MOP requirements. The noncompliance may be either on 
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deviations, corrective actions are to be developed by the site and 
implemented promptly. 
 
These practices are consistent with ICH E6: 
• 4.5. Compliance with Protocol, Sections 4.5.1, 4.5.2, and 4.5.3 
• 5.1. Quality Assurance and Quality Control, Section 5.1.1 
• 5.20 Noncompliance, Sections 5.20.1, and 5.20.2 
 
It is the responsibility of the site PI to use continuous vigilance to identify and 
report deviations within five working days of identification of the protocol 
deviation, or within five working days of the scheduled protocol-required 
activity. All deviations must be promptly reported to the lead PI or designated 
personnel. 
 
All protocol deviations, as defined above, must be addressed in study 
participant source documents. A completed copy of the Protocol Deviation 
Form must be maintained in the Regulatory File. Protocol deviations must be sent 
to the local IRB/IEC per their guidelines. The site PI/study staff is responsible for 
knowing and adhering to their IRB requirements. 
All protocol deviations must also be reported to the sponsor. A report of all 
deviations should be sent via email to the sponsor on a monthly basis. Any 
deviation that per site guidelines is considered a major deviation should be 
reported to the sponsor within 24 hours of knowledge of the deviation. 
 
 

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C.17. References 
1.  
CDC. Antibiotic Resistance Threats in the United States, 2013. Atlanta, GA: 
US Department of Health and Human Services, CDC; 2013. 
2.  
Lim CJ, Kong DC, Stuart RL. Reducing inappropriate antibiotic prescribing 
in the residential care setting: Current perspectives. Clin Interv Aging. 
2014;9:165-177. doi:10.2147/CIA.S46058. 
3.  
Trick WE, Weinstein RA, DeMarais PL, et al. Colonization of skilled-care 
facility residents with antimicrobial-resistant pathogens. J Am Geriatr Soc. 
2001;49(3):270-276. 
4.  
Loeb MB, Craven S, McGeer AJ, et al. Risk factors for resistance to 
antimicrobial agents among nursing home residents. Am J Epidemiol. 
2003;157(1):40-47. doi:10.1093/aje/kwf173. 
5.  
CDC. Core Elements of Antibiotic Stewardship for Nursing Homes. Atlanta, 
GA: US Department of Health and Human Services, CDC; 2015. 
6.  
Yates M, Horan MA, Clague JE, Gonsalkorale M, Chadwick PR, Pendleton 
N. A study of infection in elderly nursing/residential home and community-
based residents. J Hosp Infect. 1999;43(2):123-129. 
doi:10.1053/jhin.1999.0739. 
7.  
Relman DA. The human microbiome: Ecosystem resilience and health. Nutr 
Rev. 2012;70(Suppl 1):S2-S9. doi:10.1111/j.1753-4887.2012.00489.x. 
8.  
Becattini S, Taur Y, Pamer EG. Antibiotic-induced changes in the intestinal 
microbiota and disease. Trends Mol Med. 2016;22(6):458-478. 
doi:10.1016/j.molmed.2016.04.003. 
9.  
Hentges DJ, Freter R. In vivo and in vitro antagonism of intestinal bacteria 
against Shigella flexneri: I. Correlation between various tests. J Infect Dis. 
1962;110(1):30-37. doi:10.1093/infdis/110.1.30. 
10.  Freter R. In vivo and in vitro antagonism of Intestinal bacteria against 
Shigella flexneri: II. The inhibitory mechanism. J Infect Dis. 1962;110(1):38-46. 
11.  Bohnhoff M, Miller CP. Enhanced susceptibility to Salmonella infection in 
Streptomycin-treated mice. J Infect Dis. 1962;111(2):117-127. 
12.  Drekonja D, Reich J, Gezahegn S, et al. Fecal microbiota transplantation 

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for Clostridium difficile infection: A systematic review. Ann Intern Med. 
2015;162(9):630-638. doi:10.7326/M14-2693. 
13.  Agrawal M, Aroniadis OC, Brandt LJ, et al. The long-term efficacy and 
safety of fecal microbiota yransplant for recurrent, severe, and 
complicated Clostridium difficile infection in 146 elderly individuals. J Clin 
Gastroenterol. 2016;50(5):403-407. doi:10.1097/MCG.0000000000000410. 
14.  Pamer EG. Resurrecting the intestinal microbiota to combat antibiotic-
resistant pathogens. Science (80- ). 2016;352(6285):535-538. 
doi:10.1126/science.aad9382. 
15.  Halpin AL, McDonald LC. The Dawning of Microbiome Remediation for 
Addressing Antibiotic Resistance. Clin Infect Dis. March 2016:ciw187. 
doi:10.1093/cid/ciw187. 
16.  Donskey CJ, Chowdhry TK, Hecker MT, et al. Effect of antibiotic therapy on 
the density of vancomycin-resistant enterococci in the stool of colonized 
patients. N Engl J Med. 2000;343(26):1925-1932. 
doi:10.1056/NEJM200012283432604. 
17.  Johnsen PJ, Simonsen GS, Olsvik O, Midtvedt T, Sundsfjord A. Stability, 
persistence, and evolution of plasmid-encoded VanA glycopeptide 
resistance in enterococci in the absence of antibiotic selection in vitro and 
in gnotobiotic mice. Microb Drug Resist. 2002;8(3):161-170. 
doi:10.1089/107662902760326869. 
18.  Foucault M-L, Depardieu F, Courvalin P, Grillot-Courvalin C. Inducible 
expression eliminates the fitness cost of vancomycin resistance in 
enterococci. Proc Natl Acad Sci U S A. 2010;107(39):16964-16969. 
doi:10.1073/pnas.1006855107. 
19.  Ubeda C, Bucci V, Caballero S, et al. Intestinal microbiota containing 
Barnesiella species cures vancomycin-resistant Enterococcus faecium 
colonization. Infect Immun. 2013;81(3):965-973. doi:10.1128/IAI.01197-12. 
20.  Crum-Cianflone NF, Sullivan E, Ballon-Landa G. Fecal microbiota 
transplantation and successful resolution of multidrug-resistant-organism 
colonization. J Clin Microbiol. 2015;53(6):1986-1989. doi:10.1128/JCM.00820-
15. 
21.  Freedman A. Use of stool transplant to clear fecal colonization with 
carbapenem-resistant enterobacteraciae (CRE): Proof of concept. In: 

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IDSA. ; 2014. 
22.  Singh R, van Nood E, Nieuwdorp M, et al. Donor feces infusion for 
eradication of Extended Spectrum beta-Lactamase producing Escherichia 
coli in a patient with end stage renal disease. Clin Microbiol Infect Off Publ 
Eur Soc Clin Microbiol Infect Dis. 2014;20(11):O977-978. doi:10.1111/1469-
0691.12683. 
23.  Wei Y, Gong J, Zhu W, et al. Fecal microbiota transplantation restores 
dysbiosis in patients with methicillin resistant Staphylococcus aureus 
enterocolitis. BMC Infect Dis. 2015;15:265. doi:10.1186/s12879-015-0973-1. 
24.  Lombardo M-J. Vancomycin-resistant enterococcal (VRE) titers diminish 
among patients with recurrent Clostridium difficile infection after 
administration of SER-109, a novel microbiome agent. In: IDSA; 2015. 
25.  Dubois N, Ling K, Osman M, et al. Prospective assessment of donor eligibility 
for Fecal Microbiota Transplantation at a public stool bank: results from the 
evaluation of 1,387 candidate donors. In: San Diego: IDSA; 2015. 
26.  Kassam Z, Lee CH, Yuan Y, Hunt RH. Navigating long-term safety in fecal 
microbiota transplantation. Am J Gastroenterol. 2013;108(9):1538. 
doi:10.1038/ajg.2013.214. 
27.  Taur Y, Pamer EG. Autologous Fecal Microbiota Transplantation (Auto-FMT) 
for prophylaxis of Clostridium difficile infection in recipients of allogeneic 
hematopoietic stem cell transplantation. Clinical Trials Registry 
(NCT02269150). 
28.  Fischer M, Allegretti JR, Smith M, et al. A multi-center, cluster randomized 
dose-finding study of fecal microbiota transplantation capsules for 
recurrent Clostridium difficile infection. In: ; 2016. 
29.  Zipursky JS, Sidorsky TI, Freedman CA, Sidorsky MN, Kirkland KB. Patient 
attitudes toward the use of fecal microbiota transplantation in the 
treatment of recurrent Clostridium difficile infection. Clin Infect Dis. 
2012;55(12):1652-1658. doi:10.1093/cid/cis809. 
30.  Hochberg NS, Rekhtman S, Burns J, et al. The complexity of diagnosing 
latent tuberculosis infection in older adults in long-term care facilities. Int J 
Infect Dis IJID Off Publ Int Soc Infect Dis. 2016;44:37-43. 
doi:10.1016/j.ijid.2016.01.007. 

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31.  Crobach MJT, Planche T, Eckert C, et al. European Society of Clinical 
Microbiology and Infectious Diseases: update of the diagnostic guidance 
document for Clostridium difficile infection. Clin Microbiol Infect. 2016;20 
Suppl 2(Cdi):1-26. doi:10.1016/j.cmi.2016.03.010. 
32.  Claesson MJ, Jeffery IB, Conde S, et al. Gut microbiota composition 
correlates with diet and health in the elderly. Nature. 2012;488(7410):178-
184. doi:10.1038/nature11319. 
33.  Mariat D, Firmesse O, Levenez F, et al. The Firmicutes/Bacteroidetes ratio of 
the human microbiota changes with age. BMC Microbiol. 2009;9:123. 
doi:10.1186/1471-2180-9-123. 
34.  Hamilton MJ, Weingarden AR, Sadowsky MJ, Khoruts A. Standardized 
frozen preparation for transplantation of fecal microbiota for recurrent 
Clostridium difficile infection. Am J Gastroenterol. 2012;107(5):761-767. 
doi:10.1038/ajg.2011.482. 
35.  Youngster I, Mahabamunuge J, Systrom HK, et al. Oral, frozen fecal 
microbiota transplant (FMT) capsules for recurrent Clostridium difficile 
infection. BMC Med. 2016;14(1):134. doi:10.1186/s12916-016-0680-9. 
 
 
 

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C.18. Safety Reporting and Definitions 
C.18.1. Investigational New Drug Safety Reporting Definitions 
21 CFR §312.32 IND safety reporting. 
(a) Definitions. The following definitions of terms apply to this section: 
Adverse event means any untoward medical occurrence associated with 
the use of a drug in humans, whether or not considered drug related. 
Life-threatening adverse event or life-threatening suspected adverse 
reaction. An adverse event or suspected adverse reaction is considered “life-
threatening” if, in the view of the PIs, its occurrence places the patient or 
participant at immediate risk of death. It does not include an adverse event or 
suspected adverse reaction that, had it occurred in a more severe form, might 
have caused death. 
Serious adverse event or serious suspected adverse reaction. An adverse 
event or suspected adverse reaction is considered “serious” if, in the view of 
either the investigator or sponsor, it results in any of the following outcomes: 
Death, a life-threatening adverse event, inpatient hospitalization or prolongation 
of existing hospitalization, a persistent or significant incapacity or substantial 
disruption of the ability to conduct normal life functions, or a congenital 
anomaly/birth defect. Important medical events that may not result in death, 
be life-threatening, or require hospitalization may be considered serious when, 
based upon appropriate medical judgment, they may jeopardize the patient or 
participant and may require medical or surgical intervention to prevent one of 
the outcomes listed in this definition. Examples of such medical events include 
allergic bronchospasm requiring intensive treatment in an emergency room or 
at home, blood dyscrasias or convulsions that do not result in inpatient 
hospitalization, or the development of drug dependency or drug abuse. 
Suspected adverse reaction means any adverse event for which there is a 
reasonable possibility that the drug caused the adverse event. For the purposes 
of IND safety reporting, “reasonable possibility” means there is evidence to 
suggest a causal relationship between the drug and the adverse event. 
Suspected adverse reaction implies a lesser degree of certainty about causality 
than adverse reaction, which means any adverse event caused by a drug. 
Unexpected adverse event or unexpected suspected adverse reaction. An 
adverse event or suspected adverse reaction is considered “unexpected” if it is 
not listed in the investigator brochure or is not listed at the specificity or severity 
that has been observed; or, if an investigator brochure is not required or 
available, is not consistent with the risk information described in the general 
investigational plan or elsewhere in the current application, as amended. For 
example, under this definition, hepatic necrosis would be unexpected (by virtue 

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C.19. Study Design 
C.19.1. Study Design Schematic 
 
 
 
 

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C.19.2. Patient Enrollment Pipeline 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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C.20. Common Conditions in the Geriatric Population 
 
Anemia 
Angina or chest pain 
Asthma 
Atrial fibrillation 
Bipolar 
Bleeding disorder 
Blood clots / venous 
thromboembolism 
Bypass surgery 
Cancer 
Chronic Obstructive 
Pulmonary 
Disease/emphysema 
Cirrhosis 
Congestive heart failure 
Connective tissue 
disorder (lupus, 
scleroderma) 
Coronary artery disease 
Crohns Disease 
Dementia 
Depression 
Dialysis 
Dysphagia (trouble 
swallowing) 
Gout 
Heart attack/Myocardial 
Infarct 
Heart valve replacement 
Hepatitis 
Hiatial hernia 
High blood pressure 
High cholesterol 
Hip fracture 
HIV/AIDS 
Irritable bowel 
Kidney failure 
Liver disease 
Memory problems 
Neuropathy 
Palpitations 
Parkinsons 
Poor 
circulation/claudication 
Rheumatoid Arthritis 
Schizophrenia 
Seizures 
Spinal surgery 
Stomach ulcers 
Stroke 
Transient Ischaemic 
Attack (TIA) 
Type 2 Diabetes Mellitus  
Ulcerative colitis
 

Project Title: RACE  
Principle Investigators: Zain Kassam, MD, MPH, FRCPC & Christine Liu, MD, MSc 
 
Page 2 of 13 
 
Not everyone in the study will receive the actual bacteria transplant. Half the people in 
the study will have an enema that contains no fecal material (placebo). Comparing two 
groups will help the researchers learn if the bacteria transplant makes a difference in 
the development of antibiotic resistant bacteria infection. 
Taking part in this research study is voluntary. You can decide to stop taking part in this 
research study at any time for any reason. If you stop being in this research study, it will 
not affect how you are treated at the nursing home or your relations with your medical 
care team. 
Your doctor may also be an investigator in this research study. Being an investigator 
means your doctor is interested in both you and the study. You may want to get a 
second opinion about being in the study. You can do so now or at any time during the 
study. Another doctor who is not an investigator can give you a second opinion about 
being in the study. You do not have to agree to be in this study even though it is offered 
by your doctor. 
PURPOSE 
This is not a treatment study. The researchers first want to see if this type of bacteria 
transplant is safe and if it is possible to perform. In addition, there will be examinations 
to see if the bacteria transplant made a difference in the type of bacteria in your colon 
and to check the type of antibiotic resistant bacteria in your colon. 
This study would use your own friendly bacteria from your stool, which OpenBiome and 
their research collaborators will collect and store for use if you are prescribed 
antibiotics. 
WHAT WILL HAPPEN IN THIS RESEARCH STUDY 
If you agree to be in the study, you will provide us with a stool sample. If you are 
prescribed antibiotics, you will be assigned to receive a treatment of your own stool or a 
placebo. A computer will randomly choose which of the two study groups you will be 
assigned. The choice will neither be based on your decision nor the researcher’s 
decision. The placebo looks exactly like the bacteria transplant treatment, but does not 
contain stool. Placebos are used in research studies to see if the results are due to the 
study treatment or other reasons. Neither you nor the study staff will know which one 
you receive. Study staff will follow up with you for at least 6 months after the treatment. 
If you agree to participate, you will be one of 180 subjects who will be participating in 
this research. 
BMC and BU Medical Campus IRB
IRB NUMBER: H-35722
IRB APPROVAL DATE: 07/21/2018

Project Title: RACE  
Principle Investigators: Zain Kassam, MD, MPH, FRCPC & Christine Liu, MD, MSc 
 
Page 3 of 13 
 
Before You Begin the Study:  
The study staff will briefly review your health records and information to ensure that 
you are a good candidate for the study. They will discuss with you the risks and benefits 
of being in the study, and answer any questions you have regarding the study. 
 
After You Begin the Study:  
Study staff will examine your medical chart to determine your demographics, past 
medical history and allergies, current medication list, and dietary, social, travel and 
family history. A short physical exam including measuring weight and height will be 
performed. You will be asked to provide a stool sample that will be collected by the 
study staff. At the same time, we will also swab your rectum with a small swab the size 
of a Q-tip. The stool will then be cleaned and then processed to into the bacteria 
transplant and saved. We may need to collect several stool samples until there is one 
that is of adequate size to make into a transplant. After you provide a stool sample to 
process into an enema, the study team will monitor your medical records to see if you 
will be treated with antibiotics. 
 
Your Bacteria Transplant Procedure: 
If you develop an infection needing antibiotic treatment, the study team will offer you 
treatment from the study. If you decide undergo the treatment, the study team will first 
collect another stool sample and rectal swabs from you. If a stool sample is not available 
(for example due to constipation), only rectal swabs will be collected. A brief clinical 
examination will also be performed to collect vitals. 
Then you will receive the bacteria transplant via enema. This will happen within eight 
weeks of you finishing your antibiotics. You will receive either your own colon bacteria 
or a placebo. Neither you nor your physician will know which study group you are in. 
Your other treatments will remain unchanged. The bacteria transplant is the 
administration of prepared stool and water mixture from your previously provided stool 
sample. 
For the bacteria transplant, you will be asked to lie on your left hand side and a study 
doctor or nurse will administer the enema. You will be asked to try and hold the enema 
fluid this for 30 minutes if you can, continuing to rest during this time. While you are 
getting the enema, a study doctor or nurse will be with you the entire time. 
 
 
 
BMC and BU Medical Campus IRB
IRB NUMBER: H-35722
IRB APPROVAL DATE: 07/21/2018

Project Title: RACE  
Principle Investigators: Zain Kassam, MD, MPH, FRCPC & Christine Liu, MD, MSc 
 
Page 4 of 13 
 
After Your Bacteria Transplant Procedure: 
Study staff will meet you four times after you get the bacteria transplant: 
 2-4 days after your bacteria transplant 
 5-9 days after your bacteria transplant 
 23-33 days after your bacteria transplant 
 5 ½ to 6 ½ months after your bacteria transplant 
During each visit, the study team will perform a brief physical examination to evaluate 
and identify any changes in your health. We will monitor your medical chart to 
determine any changes to your medical history and any changes to your medications. 
We will also collect a stool sample and rectal swabs at each of these follow-up visits to 
allow us to learn the type of bacteria in your stool. If you are unable to provide a stool 
sample, we will only collect rectal swabs. 
Sending Study Information to Research Collaborators: 
In addition to OpenBiome and Boston Medical Center researchers having your study 
information, we will send some of your study information and/or samples to 
researchers working with us. 
These researchers may use your information and/or samples along with other 
information that they may later on develop for internal and external programs such as 
publication, future research trial design, or commercial purposes. You will not get any 
money from the programs. 
We will label all your study materials with a code instead of your name. The key to the 
code connects your name to your study information and samples. The key to the code 
will be kept at OpenBiome and will not be shared with our research collaborators. 
Unanticipated Findings: 
During the screening process, we might find out that you have problems with your 
memory or have a certain kind of bacteria in your stool. If we find these problems, we 
would like to share this information with your regular doctor, as it may affect future 
medical treatment. However, we will only share this information with your permission. 
We will suggest to your regular doctor that our findings be verified, as the test we used 
may differ from the tests they prefer. Your doctor may or may not want to change your 
medicines or current treatments depending on what they think of the test results. We 
are happy to discuss what these possible changes may be, but it is ultimately up to your 
regular doctor to make the final recommendation as they know you best. 
BMC and BU Medical Campus IRB
IRB NUMBER: H-35722
IRB APPROVAL DATE: 07/21/2018

Project Title: RACE  
Principle Investigators: Zain Kassam, MD, MPH, FRCPC & Christine Liu, MD, MSc 
 
Page 5 of 13 
 
Biorepository Bank: 
As part of your participation in this study, you will give us stool for testing. After testing 
for infectious disease and filtering the friendly bacteria for transplant, part of your 
samples may be left over. These samples would normally be thrown away. We are 
asking you to allow us to collect and store this leftover stool in a research tissue bank. 
The collection of stool is being done as part of your participation in this research study 
and would be done whether or not you give the study staff permission for your samples 
to be stored in the tissue bank. There will be no extra procedures or time commitment 
involved for allowing us to store your leftover samples. 
If you agree, the leftover samples will be frozen and sent to the bank. We are also asking 
for your permission to store some of your health information with your samples so that 
your samples can be more useful for research. We plan to continue to review your 
medical record to update your health information in the tissue bank computer 
database. We will ask that you contact us if you are required to take antibiotics in the 
future for any reason. 
Your samples and information will be used mainly to understand the general effects of 
fecal transplantation and future antibiotic use of patients who have gone through this 
procedure. The long-term goals of the research are to learn how to better understand, 
prevent, diagnose or treat frequent c diff infections. It is not possible to list every 
research project. Also, we cannot predict all of the research questions that will be 
important over the next years. As we learn more, there are new research questions and 
new types of research related to C. difficile and the microbiome. 
Your samples and information may also be used for research on other conditions (e.g. 
comparisons to other diseases). This could include a wide variety of conditions such as 
diabetes, cancer or other chronic illnesses. 
We may plan to do genetic research on the DNA in your tissue sample. DNA is the 
material that makes up your genes. All living things are made of cells. Genes are part of 
cells with instructions that tell our bodies how to work, and determine physical 
characteristics such as hair and eye color. Genes are passed from parent to child. 
There is no limit on how long OpenBiome may store your samples and information for 
research. Samples will only be released after a project is approved by a committee of 
experts who will review each request to make sure the proposed research is ethical, 
useful, and based on good science. The code linking your samples to your medical 
record may be kept indefinitely so that your samples and updated health information 
may be used for research in the future. 
BMC and BU Medical Campus IRB
IRB NUMBER: H-35722
IRB APPROVAL DATE: 07/21/2018

Project Title: RACE  
Principle Investigators: Zain Kassam, MD, MPH, FRCPC & Christine Liu, MD, MSc 
 
Page 6 of 13 
 
You have a right to withdraw your permission at any time. If you withdraw, your 
samples and information will be destroyed. However, it will not be possible to destroy 
samples and information that have already been given to researchers. If you decide to 
withdraw, you should contact the tissue bank’s staff by phone: 
. 
You will not directly benefit from research conducted on your samples stored in the 
research tissue bank. We hope that research using the samples and information will 
help us understand, prevent, treat or cure the illnesses and conditions studied. 
RISKS & DISCOMFORTS 
Most persons enrolled in the study will only donate stool and likely not have to take the 
bacteria transplant. However, if you do need to have a bacteria transplant, here are 
some important considerations of possible events: 
 Symptoms that last only for a short while and usually get better on their own: 
o Diarrhea (70%) 
o Abdominal cramps/discomfort (20%)  
o Nausea and/or vomiting (<5%)  
o Constipation (20%)  
o Excess flatulence (25%) 
o Related to enema: 
 Irritation of the perianal area, including exacerbation of any potential 
pressure ulcers in the perianal area from enema 
 Abdominal or rectal discomfort during enema administration 
 More serious symptoms:  
o Infection: Although this material has been screened for bacteria, viruses, fungi 
and parasites there is a risk of transmission of known and unknown infectious 
organisms. This will be characterized by fever, chills and possibly low blood 
pressure. There have been two cases of a bacterial infection in the blood after 
the transplant but it is unclear if this was from the bacteria transplant, and the 
patient did well on antibiotics. 
o Receiving non-autologous bacteria transplant: there is always a risk, as in any 
procedure that administers any biological product based on bodily fluids, that 
the person receives the incorrect product. In this case, this would be a bacteria 
transplant of stool from another person. 
o Inflammatory bowel disease (IBD) flare in those with underlying IBD  
o Bowel perforation due to the pressure required to administer the enema 
o Hemorrhoid bleeding from the enema may occur. We will undertake 
precautions to prevent bleeding from your hemorrhoids. 
BMC and BU Medical Campus IRB
IRB NUMBER: H-35722
IRB APPROVAL DATE: 07/21/2018

Project Title: RACE  
Principle Investigators: Zain Kassam, MD, MPH, FRCPC & Christine Liu, MD, MSc 
 
Page 7 of 13 
 
The long-term side effects of the bacteria transplant are not currently well known. 
During the study, you should report anything that you feel is relevant or causing you 
concern. There may be unknown risks or discomforts involved. 
POTENTIAL BENEFITS 
There may be a direct benefit to you if the therapy works as it is intended. The bacteria 
transplant may prevent a serious infection after taking antibiotics. If the study therapy 
does not work or you receive the placebo, you may not receive any benefit. However, 
you being in the study may help investigators learn how to improve available treatment 
in the future. 
ALTERNATIVES 
If you decide not to participate in this study and still want to prevent antibiotic resistant 
bacteria, you can try probiotics such as Culturelle capsules, which are available at local 
drug stores. However, the ability of probiotics to prevent antibiotic resistant bacteria 
has not been definitely proven. 
COSTS 
There are no costs to you for being in this research study. 
PAYMENT 
You will be compensated for your participation. Once you have completed the consent 
process, you will receive a $30 gift card. If you undergo a study intervention (treatment 
or placebo), you will receive a $70 gift card after the procedure. 
CONFIDENTIALITY 
As this study involves the use of your identifiable, personal information, there is a 
chance of a loss of confidentiality. The researchers have procedures in place to lessen 
the possibility of this happening. The research study will be conducted according to 
detailed standard operating procedures that protect patient confidentiality. We will do 
our best to keep your information safe. However, we cannot guarantee confidentiality. 
Federal and state agencies, if they are required by law or are involved in research 
oversight, may access information about you from this study including your health 
information. Such agencies may include the U.S. Department of Health and Human 
Services, the Food and Drug Administration, the National Institutes of Health, and the 
Massachusetts Department of Public Health. 
BMC and BU Medical Campus IRB
IRB NUMBER: H-35722
IRB APPROVAL DATE: 07/21/2018

Project Title: RACE  
Principle Investigators: Zain Kassam, MD, MPH, FRCPC & Christine Liu, MD, MSc 
 
Page 8 of 13 
 
The results of this research study may be published in a medical book or journal, or used 
to teach others. However, your name or other identifying information will not be used 
for these purposes without your specific permission. 
A description of this clinical trial will be available on ClinicalTrials.gov, as required by 
U.S. Law. This website will not include information that can identify you. At most, the 
website will include a summary of the results. You can search this website at any time. 
The repository has standard operating procedures to protect your confidentiality. Staff 
at the bank will assign your sample a code number and store it in a freezer. They will not 
keep your name or other information that could identify you with your sample. They will 
use the code number to connect your sample to your health information that is stored 
in a computer database. The computer database is password protected. Only staff at the 
bank will know the password. 
USE AND DISCLOSURE OF YOUR HEALTH INFORMATION 
Boston Medical Center and the study staff want to use and share your health 
information as part of this research study. The law requires Boston Medical Center to 
get your permission to do so. 
Health information that might be used or given out during this research includes: 
 Information from your hospital or office health records or elsewhere. This applies 
to information that is reasonably related to the aims, conduct and oversight of the 
research study. If health information is needed from your doctors or hospitals, we 
will ask you for permission for these records to be sent to the researcher. 
 New health information from tests, procedures, visits, interviews, or forms filled 
out as part of this research study 
The reasons that your health information might be used or given out to others are: 
 To do the research described here 
 To make sure we do the research according to certain standards set by ethics, law, 
and quality groups or otherwise as required by law 
The people and groups that may use or give out your health information are: 
 Researchers involved in this research study from Boston Medical Center  
 Researchers from other institutions or organizations that are involved in this 
research study 
 Other people at Boston Medical Center who may need to access your health 
information to do their jobs (e.g. treatment, research administration, payment, 
billing, or health care operations) 
BMC and BU Medical Campus IRB
IRB NUMBER: H-35722
IRB APPROVAL DATE: 07/21/2018

Project Title: RACE  
Principle Investigators: Zain Kassam, MD, MPH, FRCPC & Christine Liu, MD, MSc 
 
Page 9 of 13 
 
 People or groups who the researchers use to help conduct the study or provide 
oversight for the study 
 The Institutional Review Board that oversees the research and other people or 
groups who are part of the Human Research Protection Program that oversees the 
research 
 Research monitors, reviewers, or accreditation agencies and other people or 
groups that oversee research information and the safety of the study 
 The sponsor of the research study, listed on the first page, and people or groups 
hired to help them do the research 
Some people or groups who get your health information may not be obligated to follow 
the same privacy laws we follow. We ask anyone who gets your health information from 
us to protect the privacy of your information. However, after your information has been 
shared with others, we cannot promise that it will be kept private. 
The time period for using or giving out your health information: 
 Because research is an ongoing process, we cannot give you an exact date when we 
will either destroy or stop using or sharing your health information 
Your privacy rights are: 
 You have the right not to sign this form that allows us to use and give out your 
health information for research. If you do not sign this form, you cannot be in the 
research. This is because we need to use the health information to do the research. 
Your decision not to sign the form will not affect any treatment, health care, 
enrollment in health plans, or eligibility for benefits. 
 You have the right to withdraw your permission to use or share your health 
information in this research study. If you want to withdraw your permission, you 
must write a letter to the Principal Investigator at the address listed on the first 
page of this form. If you withdraw your permission, you will not be able to take 
back information that has already been used or shared with others. This includes 
information used or shared to do the research study or to be sure the research is 
safe and of high quality. If you withdraw your permission, you cannot continue to 
be in the study. 
 You have the right to see and get a copy of your health information from the 
Principal Investigator that is used or shared for research. However, you may only 
get this copy after the research is finished. 
 The results of this research study may be published in a medical book or journal, or 
used to teach others. However, your name or other identifying information will not 
be used for these purposes without your specific permission. 
BMC and BU Medical Campus IRB
IRB NUMBER: H-35722
IRB APPROVAL DATE: 07/21/2018

Project Title: RACE  
Principle Investigators: Zain Kassam, MD, MPH, FRCPC & Christine Liu, MD, MSc 
 
Page 10 of 13 
 
COMPENSATION FOR INJURY 
If you think that you have been injured by being in this study, please let the investigator 
know right away. Use the phone number on the first page of this form. You can get 
treatment for the injury at Boston Medical Center or at any healthcare facility you 
choose. There is no program to provide compensation for the cost of care for research 
related injury or for other expenses. Other expenses may include lost wages, disability, 
pain or discomfort. You or your insurance will be billed for the medical care you receive 
for a research injury. You are not giving up any of your legal rights by signing this form. 
In the event of physical injury resulting from your participation in this research, 
necessary medical treatment will be provided to you and billed as part of your medical 
expenses. Costs not covered by your health care insurer will be your responsibility. Also, 
it is your responsibility to determine the extent of your health care coverage. There is no 
program in place for other monetary compensation for such injuries. However, you are 
not giving up any legal rights or benefits to which you are otherwise entitled. If you are 
participating in research that is not conducted at a medical facility, you will be 
responsible for seeking medical care and for the expenses associated with any care 
received. 
SUBJECT’S RIGHTS 
By consenting to be in this study, you do not waive any of your legal rights. Consenting 
means that you have been given information about this study and that you agree to 
participate in the study. You will be given a copy of this form to keep. 
If you do not agree to be in this study or if you withdraw from this study at any time, 
you will not suffer any penalty or lose any benefits you are entitled. Your participation is 
completely up to you. Your decision will not affect your ability to get health care or 
payment for your health care. It will not affect your enrollment in any health plan or 
benefits you can get. 
It is important to tell the study doctor if you are thinking about stopping so any risks 
from the bacteria transplant can be evaluated by your doctor. Another reason to tell 
your doctor that you are thinking about stopping is to discuss what follow-up care and 
testing could be most helpful for you. 
During this study, we may find out something that might make you not want to stay in 
the study. If this happens, we will tell you as soon as possible.  
BMC and BU Medical Campus IRB
IRB NUMBER: H-35722
IRB APPROVAL DATE: 07/21/2018

Project Title: RACE  
Principle Investigators: Zain Kassam, MD, MPH, FRCPC & Christine Liu, MD, MSc 
 
Page 11 of 13 
 
We may decide to have you stop being in the study even if you want to stay. Your 
participation may be terminated by the investigator without regard to your consent in 
the following circumstances: 
 If he/she believes it is in your best interest or your health 
 If you experience any side effects or if you become ill during the research 
 If it is part of the research plan that people who develop certain conditions may not 
continue to participate 
 If you do not follow the study rules 
 If the study is stopped 
QUESTIONS 
The investigator or a member of the research team will try to answer all of your 
questions. If you have questions or concerns at any time, contact Christine Liu, MD, MSc 
. You may also call if you need to report an injury while being in this 
research or if you are calling after normal business hours. 
You may also call 
 or email 
. You will be talking to 
someone at the Boston Medical Center and Boston University Medical Campus IRB. The 
IRB is a group that helps monitor research. You should call or email the IRB if you want 
to find out about your rights as a research subject. You should also call or email if you 
want to talk to someone not part of the study about your questions, concerns or 
problems. 
BIOREPOSITORY BANK 
We would like to ask your permission to collect and store leftover stool for a research 
tissue bank. Please initial your choice below: 
____Yes   ____No   You may collect and store leftover stool for a research tissue bank. 
 
RE-CONTACT 
We would like to ask your permission to contact you again in the future. This contact 
would be after the study has ended. Please initial your choice below: 
 ____Yes   ____No   You may contact me again to ask for additional information related 
to this study. 
 ____Yes   ____No 
You may contact me again to ask for additional biological samples 
related to this study. 
BMC and BU Medical Campus IRB
IRB NUMBER: H-35722
IRB APPROVAL DATE: 07/21/2018

Project Title: RACE  
Principle Investigators: Zain Kassam, MD, MPH, FRCPC & Christine Liu, MD, MSc 
 
Page 12 of 13 
 
SIGNATURES 
 
Subject: ________________________________ 
Printed Name of Subject 
 
By signing this consent form, you are indicating: 
 You have read this form (or it has been read to you) 
 Your questions have been answered to your satisfaction 
 You voluntarily agree to participate in this research study 
 You permit the use and release of information that may identify you as described, 
including your health information 
 
 
To be completed by subject if personally signing 
 
_______________________________________________ 
______________ 
Signature of Subject 
 
 
 
 
 
 
Date 
 
 
 
To be completed by LAR if subject does not personally sign 
I am providing consent on behalf of the subject. 
 
_______________________________________________ 
____________________  
Printed Name of Legally Authorized Representative (LAR) 
Relationship to Subject 
 
_______________________________________________ 
______________ 
Signature of LAR  
 
 
 
 
 
 
Date 
 
 
 
 
 
 
 
 
 
BMC and BU Medical Campus IRB
IRB NUMBER: H-35722
IRB APPROVAL DATE: 07/21/2018

Project Title: RACE  
Principle Investigators: Zain Kassam, MD, MPH, FRCPC & Christine Liu, MD, MSc 
 
Page 13 of 13 
 
 
Researcher: ______________________________________________ 
Printed Name of Person Conducting Consent Discussion 
 
 
To be completed by researcher if subject personally signs 
I have personally explained the research to the above-named subject and answered all 
questions. I believe that the subject understands what is involved in the study and freely 
agrees to participate. 
 
_______________________________________________ 
______________ 
Signature of Person Conducting Consent Discussion 
 
Date 
 
 
 
To be completed by researcher if subject does not personally sign 
I have personally explained the research to the above-named subject’s Legally 
Authorized Representative (LAR) and answered all questions. I believe that the LAR 
understands what is involved in the study and freely agrees to have the subject 
participate. 
 
I consider that the above-named subject who is being enrolled in the study (check one): 
 is capable of understanding what is involved in the study and freely agrees to 
participate. 
 is not capable of understanding what is involved in the study. 
 
_______________________________________________ 
______________ 
Signature of Person Conducting Consent Discussion 
 
Date 
 
 
 
To be completed by witness if researcher reads this form to the subject/LAR 
 
_______________________________________________ 
Printed Name of Witness (a person not otherwise associated with this study) 
 
_______________________________________________ 
______________ 
Signature of Person Conducting Consent Discussion 
 
Date 
BMC and BU Medical Campus IRB
IRB NUMBER: H-35722
IRB APPROVAL DATE: 07/21/2018