Penn Microbiome Therapy (PMT) for Severe-Clostridium Diff... | NCT03970200

Label	Type	Description	Intervention Names
No investigational product	Active Comparator	Participants who receive the antibiotics usually prescribed for C diff infection.	Drug: Antibiotics
Upper gastrointestinal Fecal Microbiota Transplantation	Experimental	Participants who receive the antibiotics usually prescribed for C diff infection, along with PMT that is given by mouth in capsules or through a tube that goes into your stomach/intestines if you already have one (upper delivery). You will not be assigned to this group if you cannot take any medications either by mouth or through a tube safely, as determined by your doctor	Drug: Penn Microbiome Therapy - 002 Drug: Penn Microbiome Therapy - 003 Drug: Antibiotics
Lower gastrointestinal Fecal Microbiota Transplantation	Experimental	Participants who receive the antibiotics usually prescribed for C diff infection, along with PMT that is given through the rectum by an enema (lower delivery).	Drug: Penn Microbiome Therapy - 001 Drug: Antibiotics

Name	Type	Description	Arm Group Labels	Other Names
Penn Microbiome Therapy - 001	Drug	Fecal Microbiota for Transplant, enema product	Lower gastrointestinal Fecal Microbiota Transplantation

Measure	Description	Time Frame
Number of Subjects With Resolution of Symptoms After Treatment With One of the PMT Suite of Products.	The outcome will be satisfied when the subject is discharged from the hospital (not to hospice or palliative care) or, while the subject remains hospitalized, when the following criteria are met for 72 hours: If radiology study or studies performed, ileus/dilation/megacolon either not noted or noted as resolved Ileus/megacolon either noted as resolved by any provider documentation or not noted White Blood Cells (WBC) <15,000 cells/uL Serum creatinine decreased, unchanged, or increased by ≤0.2 mg/dL over 72 hours (if not receiving continuous renal replacement therapy (CRRT) or hemodialysis (HD)) Lactate ≤2.2 mmol/L (if measured by clinical care team) No vasopressors used (including epinephrine, norepinephrine, phenylephrine, or vasopressin) Temperature <38.5 °C and ≥35.6°C < 8 bowel movements per day and < 600 mL unformed stool (if volume recorded) Meeting fewer than 3 systemic inflammatory response syndrome (SIRS) criteria	3 Days

Measure	Description	Time Frame
All-cause Mortality at 30 Days Following Last Fecal Microbiota Transplantation (FMT)	Number of deaths within 30 days of the last FMT	30 Days
All-cause Mortality at 60-days Following Last FMT

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

1. One or more episodes of CDI with symptoms including bowel movements altered in frequency or consistency from baseline.
2. Stool test positive for Clostridium difficile by enzyme immunoassay (EIA) by FDA-cleared assay within 7 days prior to enrollment.
3. Age ≥ 18 years
4. Meets any one of the listed criteria for severe or severe-complicated/fulminant disease within 72 hours of enrollment.
5. Receiving antibiotic treatment for S/SC(Severe-complicatedcategory)/F-CDI per current Infectious Diseases Society of America(IDSA) guidelines.

Enrollment criteria details:

1. Must either meet ≥1 criteria in severe category or in severe complicated category to be enrolled
2. If the subject meets criteria in both categories, stratify to the higher severity category (severe complicated)
3. Detailed enrollment criteria definitions:
a. white blood cells (WBC) ≥15,000 cells/uL - if any value in the time period meets this definition
b. Hypotension with systolic blood pressure sustained < 90mmHg for three or more hours or requiring vasopressors (epinephrine, norepinephrine, phenylephrine, or vasopressin)
c. Acute kidney injury - increase in serum creatinine level by ≥50% or new dialysis initiation
i. If a baseline serum creatinine value is not available, acute kidney injury will be defined as a serum creatinine >1.5 mg/dL
d. Temperature ≥38.5 °C or <35.6°C - one value needed in time period -
e. Ileus, bowel dilation or megacolon
i. Ileus: If noted in any provider documentation or problem list (search words "ileus") OR
ii. If the words "dilated" "dilation" or "ileus" are noted in a radiology report on intestines/colon, or if "megacolon" noted
f. Lactate >2.2 mmol/L - if any value in the time period meets this definition
g. Systemic inflammatory response syndrome(SIRS) criteria
i. Heart rate > 90 beats per minute
ii. Respiratory rate > 20 breaths per minute or PaCO2 < 32 mmHg
iii. Temperature >38ºC or <36ºC
iv. WBC > 12,000 cells/uL, <4,000 cells/uL, or >10% immature (band) forms

Exclusion Criteria:

1. Evidence of colon/small bowel perforation at the time of study screening.
2. Goals of care are directed to comfort rather than curative measures.
3. Moderate (ANC < 1000 cells/uL) or severe (ANC < 500 cells/uL) neutropenia.
4. Known food allergy that could lead to anaphylaxis.
5. Pregnancy
a. For subjects of childbearing potential (ages 18 to 55), the subject must have a negative urine pregnancy test within 48 hours of consent and no more than 48 hours prior to first product administration.
6 Receipt of Fecal Microbiota Transplantation (FMT) or enrollment in a clinical trial for FMT within the last 3 months.
7 COVID-19 infection, as defined by a positive nucleic acid or antigen test within the prior 14 days and symptoms consistent with COVID-19 infection

Name	Affiliation	Role
Ebbing Lautenbach, MD, MPH, MSCE	Division of Infectious Diseases, Department of Medicine, University of Pennsylvania	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Hospital of the Univeristy of Pennsylvania		Philadelphia	Pennsylvania	19104	United States

ID	Title	Description
FG000	No Investigational Product	Participants who receive the antibiotics usually prescribed for C diff infection. Antibiotics: Standard of care antibiotics
FG001	Upper Gastrointestinal Fecal Microbiota Transplantation

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Jun 8, 2021

ID	Title	Description
BG000	No Investigational Product	Participants who receive the antibiotics usually prescribed for C diff infection. Antibiotics: Standard of care antibiotics
BG001	Upper Gastrointestinal Fecal Microbiota Transplantation	Participants who receive the antibiotics usually prescribed for C diff infection, along with PMT that is given by mouth in capsules or through a tube that goes into your stomach/intestines if you already have one (upper delivery). You will not be assigned to this group if you cannot take any medications either by mouth or through a tube safely, as determined by your doctor Penn Microbiome Therapy - 002: Fecal Microbiota for Transplant, suspension product Penn Microbiome Therapy - 003: Fecal Microbiota for Transplant, capsule product Antibiotics: Standard of care antibiotics
BG002	Lower Gastrointestinal Fecal Microbiota Transplantation	Participants who receive the antibiotics usually prescribed for C diff infection, along with PMT that is given through the rectum by an enema (lower delivery). Penn Microbiome Therapy - 001: Fecal Microbiota for Transplant, enema product Antibiotics: Standard of care antibiotics
BG003	Total	Total of all reporting groups

Units	Counts
Participants	BG0005 BG0014 BG0026 BG00315

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Subjects With Resolution of Symptoms After Treatment With One of the PMT Suite of Products.

The outcome will be satisfied when the subject is discharged from the hospital (not to hospice or palliative care) or, while the subject remains hospitalized, when the following criteria are met for 72 hours:

If radiology study or studies performed, ileus/dilation/megacolon either not noted or noted as resolved
Ileus/megacolon either noted as resolved by any provider documentation or not noted
White Blood Cells (WBC) <15,000 cells/uL
Serum creatinine decreased, unchanged, or increased by ≤0.2 mg/dL over 72 hours (if not receiving continuous renal replacement therapy (CRRT) or hemodialysis (HD))
Lactate ≤2.2 mmol/L (if measured by clinical care team)
No vasopressors used (including epinephrine, norepinephrine, phenylephrine, or vasopressin)
Temperature <38.5 °C and ≥35.6°C
< 8 bowel movements per day and < 600 mL unformed stool (if volume recorded)
Meeting fewer than 3 systemic inflammatory response syndrome (SIRS) criteria

Posted

Count of Participants

Participants

3 Days

ID	Title	Description
OG000	No Investigational Product	Participants who receive the antibiotics usually prescribed for C diff infection. Antibiotics: Standard of care antibiotics
OG001	Upper Gastrointestinal Fecal Microbiota Transplantation	Participants who receive the antibiotics usually prescribed for C diff infection, along with PMT that is given by mouth in capsules or through a tube that goes into your stomach/intestines if you already have one (upper delivery). You will not be assigned to this group if you cannot take any medications either by mouth or through a tube safely, as determined by your doctor Penn Microbiome Therapy - 002: Fecal Microbiota for Transplant, suspension product Penn Microbiome Therapy - 003: Fecal Microbiota for Transplant, capsule product Antibiotics: Standard of care antibiotics
OG002	Lower Gastrointestinal Fecal Microbiota Transplantation	Participants who receive the antibiotics usually prescribed for C diff infection, along with PMT that is given through the rectum by an enema (lower delivery). Penn Microbiome Therapy - 001: Fecal Microbiota for Transplant, enema product Antibiotics: Standard of care antibiotics

Units	Counts
Participants	OG0005 OG0014 OG0026

Title

Denominators

Categories

Title	Measurements
	OG0004 OG0013 OG0025

Secondary

All-cause Mortality at 30 Days Following Last Fecal Microbiota Transplantation (FMT)

Number of deaths within 30 days of the last FMT

Posted

Count of Participants

Participants

30 Days

ID	Title	Description
OG000	No Investigational Product	Participants who receive the antibiotics usually prescribed for C diff infection. Antibiotics: Standard of care antibiotics
OG001	Upper Gastrointestinal Fecal Microbiota Transplantation	Participants who receive the antibiotics usually prescribed for C diff infection, along with PMT that is given by mouth in capsules or through a tube that goes into your stomach/intestines if you already have one (upper delivery). You will not be assigned to this group if you cannot take any medications either by mouth or through a tube safely, as determined by your doctor Penn Microbiome Therapy - 002: Fecal Microbiota for Transplant, suspension product Penn Microbiome Therapy - 003: Fecal Microbiota for Transplant, capsule product Antibiotics: Standard of care antibiotics
OG002	Lower Gastrointestinal Fecal Microbiota Transplantation	Participants who receive the antibiotics usually prescribed for C diff infection, along with PMT that is given through the rectum by an enema (lower delivery). Penn Microbiome Therapy - 001: Fecal Microbiota for Transplant, enema product Antibiotics: Standard of care antibiotics

Secondary

All-cause Mortality at 60-days Following Last FMT

Number of deaths within 60 days of the last FMT

Posted

Count of Participants

Participants

60 Days

ID	Title	Description
OG000	No Investigational Product	Participants who receive the antibiotics usually prescribed for C diff infection. Antibiotics: Standard of care antibiotics
OG001	Upper Gastrointestinal Fecal Microbiota Transplantation	Participants who receive the antibiotics usually prescribed for C diff infection, along with PMT that is given by mouth in capsules or through a tube that goes into your stomach/intestines if you already have one (upper delivery). You will not be assigned to this group if you cannot take any medications either by mouth or through a tube safely, as determined by your doctor Penn Microbiome Therapy - 002: Fecal Microbiota for Transplant, suspension product Penn Microbiome Therapy - 003: Fecal Microbiota for Transplant, capsule product Antibiotics: Standard of care antibiotics
OG002	Lower Gastrointestinal Fecal Microbiota Transplantation	Participants who receive the antibiotics usually prescribed for C diff infection, along with PMT that is given through the rectum by an enema (lower delivery). Penn Microbiome Therapy - 001: Fecal Microbiota for Transplant, enema product Antibiotics: Standard of care antibiotics

Secondary

Colectomy or Diverting Ileostomy Within 30 Days After Last FMT

Posted

Count of Participants

Participants

30 Days

ID	Title	Description
OG000	No Investigational Product	Participants who receive the antibiotics usually prescribed for C diff infection. Antibiotics: Standard of care antibiotics
OG001	Upper Gastrointestinal Fecal Microbiota Transplantation	Participants who receive the antibiotics usually prescribed for C diff infection, along with PMT that is given by mouth in capsules or through a tube that goes into your stomach/intestines if you already have one (upper delivery). You will not be assigned to this group if you cannot take any medications either by mouth or through a tube safely, as determined by your doctor Penn Microbiome Therapy - 002: Fecal Microbiota for Transplant, suspension product Penn Microbiome Therapy - 003: Fecal Microbiota for Transplant, capsule product Antibiotics: Standard of care antibiotics
OG002	Lower Gastrointestinal Fecal Microbiota Transplantation	Participants who receive the antibiotics usually prescribed for C diff infection, along with PMT that is given through the rectum by an enema (lower delivery). Penn Microbiome Therapy - 001: Fecal Microbiota for Transplant, enema product Antibiotics: Standard of care antibiotics

Secondary

Cumulative Days of Hospitalization From Enrollment Until 30 Days After FMT

Posted

Median

Full Range

days

30 Days

ID	Title	Description
OG000	No Investigational Product	Participants who receive the antibiotics usually prescribed for C diff infection. Antibiotics: Standard of care antibiotics
OG001	Upper Gastrointestinal Fecal Microbiota Transplantation	Participants who receive the antibiotics usually prescribed for C diff infection, along with PMT that is given by mouth in capsules or through a tube that goes into your stomach/intestines if you already have one (upper delivery). You will not be assigned to this group if you cannot take any medications either by mouth or through a tube safely, as determined by your doctor Penn Microbiome Therapy - 002: Fecal Microbiota for Transplant, suspension product Penn Microbiome Therapy - 003: Fecal Microbiota for Transplant, capsule product Antibiotics: Standard of care antibiotics
OG002	Lower Gastrointestinal Fecal Microbiota Transplantation	Participants who receive the antibiotics usually prescribed for C diff infection, along with PMT that is given through the rectum by an enema (lower delivery). Penn Microbiome Therapy - 001: Fecal Microbiota for Transplant, enema product Antibiotics: Standard of care antibiotics

Secondary

Cumulative Days in Intensive Care Unit From Enrollment Until 30 Days After Last FMT

Posted

Median

Full Range

days

30 Days

ID	Title	Description
OG000	No Investigational Product	Participants who receive the antibiotics usually prescribed for C diff infection. Antibiotics: Standard of care antibiotics
OG001	Upper Gastrointestinal Fecal Microbiota Transplantation	Participants who receive the antibiotics usually prescribed for C diff infection, along with PMT that is given by mouth in capsules or through a tube that goes into your stomach/intestines if you already have one (upper delivery). You will not be assigned to this group if you cannot take any medications either by mouth or through a tube safely, as determined by your doctor Penn Microbiome Therapy - 002: Fecal Microbiota for Transplant, suspension product Penn Microbiome Therapy - 003: Fecal Microbiota for Transplant, capsule product Antibiotics: Standard of care antibiotics
OG002	Lower Gastrointestinal Fecal Microbiota Transplantation	Participants who receive the antibiotics usually prescribed for C diff infection, along with PMT that is given through the rectum by an enema (lower delivery). Penn Microbiome Therapy - 001: Fecal Microbiota for Transplant, enema product Antibiotics: Standard of care antibiotics

Secondary

Bacteremia From Enrollment Until 30 Days After Last FMT

Posted

Count of Participants

Participants

30 Days

ID	Title	Description
OG000	No Investigational Product	Participants who receive the antibiotics usually prescribed for C diff infection. Antibiotics: Standard of care antibiotics
OG001	Upper Gastrointestinal Fecal Microbiota Transplantation	Participants who receive the antibiotics usually prescribed for C diff infection, along with PMT that is given by mouth in capsules or through a tube that goes into your stomach/intestines if you already have one (upper delivery). You will not be assigned to this group if you cannot take any medications either by mouth or through a tube safely, as determined by your doctor Penn Microbiome Therapy - 002: Fecal Microbiota for Transplant, suspension product Penn Microbiome Therapy - 003: Fecal Microbiota for Transplant, capsule product Antibiotics: Standard of care antibiotics
OG002	Lower Gastrointestinal Fecal Microbiota Transplantation	Participants who receive the antibiotics usually prescribed for C diff infection, along with PMT that is given through the rectum by an enema (lower delivery). Penn Microbiome Therapy - 001: Fecal Microbiota for Transplant, enema product Antibiotics: Standard of care antibiotics

Secondary

Repeat Hospital Admission Within 60 Days of Discharge From Index Hospitalization

Posted

Count of Participants

Participants

60 Days

ID	Title	Description
OG000	No Investigational Product	Participants who receive the antibiotics usually prescribed for C diff infection. Antibiotics: Standard of care antibiotics
OG001	Upper Gastrointestinal Fecal Microbiota Transplantation	Participants who receive the antibiotics usually prescribed for C diff infection, along with PMT that is given by mouth in capsules or through a tube that goes into your stomach/intestines if you already have one (upper delivery). You will not be assigned to this group if you cannot take any medications either by mouth or through a tube safely, as determined by your doctor Penn Microbiome Therapy - 002: Fecal Microbiota for Transplant, suspension product Penn Microbiome Therapy - 003: Fecal Microbiota for Transplant, capsule product Antibiotics: Standard of care antibiotics
OG002	Lower Gastrointestinal Fecal Microbiota Transplantation	Participants who receive the antibiotics usually prescribed for C diff infection, along with PMT that is given through the rectum by an enema (lower delivery). Penn Microbiome Therapy - 001: Fecal Microbiota for Transplant, enema product Antibiotics: Standard of care antibiotics

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	No Investigational Product	Participants who receive the antibiotics usually prescribed for C diff infection. Antibiotics: Standard of care antibiotics	2	5	3	5	4	5
EG001	Upper Gastrointestinal Fecal Microbiota Transplantation	Participants who receive the antibiotics usually prescribed for C diff infection, along with PMT that is given by mouth in capsules or through a tube that goes into your stomach/intestines if you already have one (upper delivery). You will not be assigned to this group if you cannot take any medications either by mouth or through a tube safely, as determined by your doctor Penn Microbiome Therapy - 002: Fecal Microbiota for Transplant, suspension product Penn Microbiome Therapy - 003: Fecal Microbiota for Transplant, capsule product Antibiotics: Standard of care antibiotics	2	4	3	4	4	4
EG002	Lower Gastrointestinal Fecal Microbiota Transplantation	Participants who receive the antibiotics usually prescribed for C diff infection, along with PMT that is given through the rectum by an enema (lower delivery). Penn Microbiome Therapy - 001: Fecal Microbiota for Transplant, enema product Antibiotics: Standard of care antibiotics	1	6	4	6	6	6

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Leukocytosis	Blood and lymphatic system disorders	CTCAE (5.0)	Systematic Assessment		EG0000 events0 affected5 at risk EG0010 events0 affected4 at risk EG0021 events1 affected6 at risk
Heart failure	Cardiac disorders	CTCAE (5.0)	Systematic Assessment		EG0000 events0 affected5 at risk EG0010 events0 affected4 at risk EG0022 events1 affected6 at risk
Left ventricular systolic dysfunction	Cardiac disorders	CTCAE (5.0)	Systematic Assessment		EG0000 events0 affected5 at risk EG0011 events1 affected4 at risk EG0020 events0 affected6 at risk
Diarrhea	Gastrointestinal disorders	CTCAE (5.0)	Systematic Assessment		EG0000 events0 affected5 at risk EG0010 events0 affected4 at risk EG0021 events1 affected6 at risk
Enterocolitis	Gastrointestinal disorders	CTCAE (5.0)	Systematic Assessment		EG0000 events0 affected5 at risk EG0011 events1 affected4 at risk EG0020 events0 affected6 at risk
Lower gastrointestinal hemorrhage	Gastrointestinal disorders	CTCAE (5.0)	Systematic Assessment		EG0001 events1 affected5 at risk EG0010 events0 affected4 at risk EG0021 events1 affected6 at risk
Death NOS	General disorders	CTCAE (5.0)	Systematic Assessment		EG0002 events2 affected5 at risk EG0012 events2 affected4 at risk EG0021 events1 affected6 at risk
Edema limbs	Gastrointestinal disorders	CTCAE (5.0)	Systematic Assessment		EG0000 events0 affected5 at risk EG0010 events0 affected4 at risk EG0021 events1 affected6 at risk
Hypothermia	General disorders	CTCAE (5.0)	Systematic Assessment		EG0000 events0 affected5 at risk EG0011 events1 affected4 at risk EG0020 events0 affected6 at risk
Urinary tract infection	Infections and infestations	CTCAE (5.0)	Systematic Assessment		EG0000 events0 affected5 at risk EG0012 events1 affected4 at risk EG0020 events0 affected6 at risk
Spinal fracture	Injury, poisoning and procedural complications	CTCAE (5.0)	Systematic Assessment		EG0000 events0 affected5 at risk EG0010 events0 affected4 at risk EG0021 events1 affected6 at risk
Platelet count decreased	Investigations	CTCAE (5.0)	Systematic Assessment		EG0000 events0 affected5 at risk EG0010 events0 affected4 at risk EG0021 events1 affected6 at risk
Acidosis	Metabolism and nutrition disorders	CTCAE (5.0)	Systematic Assessment		EG0000 events0 affected5 at risk EG0011 events1 affected4 at risk EG0020 events0 affected6 at risk
Hyperglycemia	Metabolism and nutrition disorders	CTCAE (5.0)	Systematic Assessment		EG0000 events0 affected5 at risk EG0010 events0 affected4 at risk EG0021 events1 affected6 at risk
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	CTCAE (5.0)	Systematic Assessment	Adenocarcinoma	EG0000 events0 affected5 at risk EG0010 events0 affected4 at risk EG0021 events1 affected6 at risk
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	CTCAE (5.0)	Systematic Assessment	Left lung adenocarcinom	EG0000 events0 affected5 at risk EG0010 events0 affected4 at risk EG0021 events1 affected6 at risk
Ischemia cerebrovascular	Nervous system disorders	CTCAE (5.0)	Systematic Assessment		EG0001 events1 affected5 at risk EG0010 events0 affected4 at risk EG0020 events0 affected6 at risk
Acute kidney injury	Renal and urinary disorders	CTCAE (5.0)	Systematic Assessment		EG0000 events0 affected5 at risk EG0012 events1 affected4 at risk EG0021 events1 affected6 at risk
Urinary retention	Renal and urinary disorders	CTCAE (5.0)	Systematic Assessment		EG0000 events0 affected5 at risk EG0010 events0 affected4 at risk EG0021 events1 affected6 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	CTCAE (5.0)	Systematic Assessment		EG0001 events1 affected5 at risk EG0010 events0 affected4 at risk EG0021 events1 affected6 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	CTCAE (5.0)	Systematic Assessment		EG0000 events0 affected5 at risk EG0011 events1 affected4 at risk EG0020 events0 affected6 at risk
Hypotension	Vascular disorders	CTCAE (5.0)	Systematic Assessment		EG0001 events1 affected5 at risk EG0011 events1 affected4 at risk EG0020 events0 affected6 at risk
Thromboembolic event	Vascular disorders	CTCAE (5.0)	Systematic Assessment		EG0000 events0 affected5 at risk EG0011 events1 affected4 at risk EG0020 events0 affected6 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Leukocytosis	Blood and lymphatic system disorders	CTCAE (5.0)	Systematic Assessment		EG0002 events2 affected5 at risk EG0010 events0 affected4 at risk EG0023 events3 affected6 at risk
Anemia	Blood and lymphatic system disorders	CTCAE (5.0)	Systematic Assessment		EG0001 events1 affected5 at risk EG0010 events0 affected4 at risk EG0020 events0 affected6 at risk
Blood and lymphatic system disorders - Other	Blood and lymphatic system disorders	CTCAE (5.0)	Systematic Assessment	Splenomegaly	EG0000 events0 affected5 at risk EG0010 events0 affected4 at risk EG0021 events1 affected6 at risk
Blood and lymphatic system disorders - Other	Blood and lymphatic system disorders	CTCAE (5.0)	Systematic Assessment	Thrombocytopenia and Leukopenia	EG0000 events0 affected5 at risk EG0010 events0 affected4 at risk EG0021 events1 affected6 at risk
Eosinophilia	Blood and lymphatic system disorders	CTCAE (5.0)	Systematic Assessment		EG0001 events1 affected5 at risk EG0010 events0 affected4 at risk EG0020 events0 affected6 at risk
Atrial fibrillation	Cardiac disorders	CTCAE (5.0)	Systematic Assessment		EG0000 events0 affected5 at risk EG0011 events1 affected4 at risk EG0021 events1 affected6 at risk
Heart failure	Cardiac disorders	CTCAE (5.0)	Systematic Assessment		EG0000 events0 affected5 at risk EG0011 events1 affected4 at risk EG0021 events1 affected6 at risk
Endocrine disorders - Other	Endocrine disorders	CTCAE (5.0)	Systematic Assessment	Diabetes	EG0000 events0 affected5 at risk EG0010 events0 affected4 at risk EG0021 events1 affected6 at risk
Hypothyroidism	Endocrine disorders	CTCAE (5.0)	Systematic Assessment		EG0000 events0 affected5 at risk EG0011 events1 affected4 at risk EG0020 events0 affected6 at risk
Blurred vision	Eye disorders	CTCAE (5.0)	Systematic Assessment		EG0000 events0 affected5 at risk EG0010 events0 affected4 at risk EG0021 events1 affected6 at risk
Abdominal distension	Gastrointestinal disorders	CTCAE (5.0)	Systematic Assessment		EG0001 events1 affected5 at risk EG0010 events0 affected4 at risk EG0023 events2 affected6 at risk
Abdominal pain	Gastrointestinal disorders	CTCAE (5.0)	Systematic Assessment		EG0000 events0 affected5 at risk EG0011 events1 affected4 at risk EG0021 events1 affected6 at risk
Bloating	Gastrointestinal disorders	CTCAE (5.0)	Systematic Assessment		EG0000 events0 affected5 at risk EG0010 events0 affected4 at risk EG0021 events1 affected6 at risk
Constipation	Gastrointestinal disorders	CTCAE (5.0)	Systematic Assessment		EG0000 events0 affected5 at risk EG0011 events1 affected4 at risk EG0020 events0 affected6 at risk
Diarrhea	Gastrointestinal disorders	CTCAE (5.0)	Systematic Assessment		EG0002 events2 affected5 at risk EG0015 events2 affected4 at risk EG0023 events3 affected6 at risk
Enterocolitis	Gastrointestinal disorders	CTCAE (5.0)	Systematic Assessment		EG0000 events0 affected5 at risk EG0011 events1 affected4 at risk EG0024 events2 affected6 at risk
Flatulence	Gastrointestinal disorders	CTCAE (5.0)	Systematic Assessment		EG0001 events1 affected5 at risk EG0012 events2 affected4 at risk EG0021 events1 affected6 at risk
Lower gastrointestinal hemorrhage	Gastrointestinal disorders	CTCAE (5.0)	Systematic Assessment		EG0001 events1 affected5 at risk EG0010 events0 affected4 at risk EG0020 events0 affected6 at risk
Nausea	Gastrointestinal disorders	CTCAE (5.0)	Systematic Assessment		EG0000 events0 affected5 at risk EG0012 events2 affected4 at risk EG0021 events1 affected6 at risk
Vomiting	Gastrointestinal disorders	CTCAE (5.0)	Systematic Assessment		EG0001 events1 affected5 at risk EG0011 events1 affected4 at risk EG0020 events0 affected6 at risk
Edema limbs	General disorders	CTCAE (5.0)	Systematic Assessment		EG0001 events1 affected5 at risk EG0010 events0 affected4 at risk EG0020 events0 affected6 at risk
Fatigue	General disorders	CTCAE (5.0)	Systematic Assessment		EG0000 events0 affected5 at risk EG0011 events1 affected4 at risk EG0020 events0 affected6 at risk
Hypothermia	General disorders	CTCAE (5.0)	Systematic Assessment		EG0001 events1 affected5 at risk EG0011 events1 affected4 at risk EG0021 events1 affected6 at risk
Malaise	General disorders	CTCAE (5.0)	Systematic Assessment		EG0000 events0 affected5 at risk EG0010 events0 affected4 at risk EG0021 events1 affected6 at risk
Herpes simplex reactivation	Infections and infestations	CTCAE (5.0)	Systematic Assessment		EG0000 events0 affected5 at risk EG0010 events0 affected4 at risk EG0021 events1 affected6 at risk
Infections and infestations-Other	Infections and infestations	CTCAE (5.0)	Systematic Assessment	Bacteriuria	EG0000 events0 affected5 at risk EG0010 events0 affected4 at risk EG0024 events1 affected6 at risk
Pharyngitis	Infections and infestations	CTCAE (5.0)	Systematic Assessment		EG0000 events0 affected5 at risk EG0010 events0 affected4 at risk EG0021 events1 affected6 at risk
Upper respiratory infection	Infections and infestations	CTCAE (5.0)	Systematic Assessment		EG0000 events0 affected5 at risk EG0010 events0 affected4 at risk EG0022 events2 affected6 at risk
Urinary tract infection	Infections and infestations	CTCAE (5.0)	Systematic Assessment		EG0000 events0 affected5 at risk EG0010 events0 affected4 at risk EG0021 events1 affected6 at risk
Spinal fracture	Injury, poisoning and procedural complications	CTCAE (5.0)	Systematic Assessment		EG0000 events0 affected5 at risk EG0011 events1 affected4 at risk EG0020 events0 affected6 at risk
Alkaline phosphatase increased	Investigations	CTCAE (5.0)	Systematic Assessment		EG0000 events0 affected5 at risk EG0011 events1 affected4 at risk EG0020 events0 affected6 at risk
Aspartate aminotransferase increased	Investigations	CTCAE (5.0)	Systematic Assessment		EG0000 events0 affected5 at risk EG0011 events1 affected4 at risk EG0020 events0 affected6 at risk
Blood bilirubin increased	Investigations	CTCAE (5.0)	Systematic Assessment		EG0000 events0 affected5 at risk EG0011 events1 affected4 at risk EG0020 events0 affected6 at risk
Cardiac troponin T increased	Investigations	CTCAE (5.0)	Systematic Assessment		EG0000 events0 affected5 at risk EG0011 events1 affected4 at risk EG0020 events0 affected6 at risk
INR increased	Investigations	CTCAE (5.0)	Systematic Assessment		EG0000 events0 affected5 at risk EG0011 events1 affected4 at risk EG0020 events0 affected6 at risk
Lipase increased	Investigations	CTCAE (5.0)	Systematic Assessment		EG0001 events1 affected5 at risk EG0010 events0 affected4 at risk EG0020 events0 affected6 at risk
Platelet count decreased	Investigations	CTCAE (5.0)	Systematic Assessment		EG0001 events1 affected5 at risk EG0010 events0 affected4 at risk EG0020 events0 affected6 at risk
Weight gain	Investigations	CTCAE (5.0)	Systematic Assessment		EG0000 events0 affected5 at risk EG0010 events0 affected4 at risk EG0021 events1 affected6 at risk
Weight loss	Investigations	CTCAE (5.0)	Systematic Assessment		EG0000 events0 affected5 at risk EG0010 events0 affected4 at risk EG0021 events1 affected6 at risk
White blood cell decreased	Investigations	CTCAE (5.0)	Systematic Assessment		EG0000 events0 affected5 at risk EG0010 events0 affected4 at risk EG0021 events1 affected6 at risk
Hyperglycemia	Metabolism and nutrition disorders	CTCAE (5.0)	Systematic Assessment		EG0000 events0 affected5 at risk EG0010 events0 affected4 at risk EG0021 events1 affected6 at risk
Hypocalcemia	Metabolism and nutrition disorders	CTCAE (5.0)	Systematic Assessment		EG0000 events0 affected5 at risk EG0011 events1 affected4 at risk EG0023 events1 affected6 at risk
Hypoglycemia	Metabolism and nutrition disorders	CTCAE (5.0)	Systematic Assessment		EG0000 events0 affected5 at risk EG0010 events0 affected4 at risk EG0022 events2 affected6 at risk
Hyponatremia	Metabolism and nutrition disorders	CTCAE (5.0)	Systematic Assessment		EG0000 events0 affected5 at risk EG0010 events0 affected4 at risk EG0022 events2 affected6 at risk
Neoplasms benign, malignant and unspecified (incl cysts and polyps)-Other	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	CTCAE (5.0)	Systematic Assessment	Glioblastoma (progression)	EG0001 events1 affected5 at risk EG0010 events0 affected4 at risk EG0020 events0 affected6 at risk
Headache	Nervous system disorders	CTCAE (5.0)	Systematic Assessment		EG0000 events0 affected5 at risk EG0011 events1 affected4 at risk EG0021 events1 affected6 at risk
Lethargy	Nervous system disorders	CTCAE (5.0)	Systematic Assessment		EG0001 events1 affected5 at risk EG0010 events0 affected4 at risk EG0020 events0 affected6 at risk
Delirium	Psychiatric disorders	CTCAE (5.0)	Systematic Assessment		EG0000 events0 affected5 at risk EG0010 events0 affected4 at risk EG0021 events1 affected6 at risk
Acute kidney injury	Renal and urinary disorders	CTCAE (5.0)	Systematic Assessment		EG0000 events0 affected5 at risk EG0010 events0 affected4 at risk EG0022 events2 affected6 at risk
Genital edema	Reproductive system and breast disorders	CTCAE (5.0)	Systematic Assessment		EG0001 events1 affected5 at risk EG0010 events0 affected4 at risk EG0020 events0 affected6 at risk
Cough	Respiratory, thoracic and mediastinal disorders	CTCAE (5.0)	Systematic Assessment		EG0000 events0 affected5 at risk EG0010 events0 affected4 at risk EG0021 events1 affected6 at risk
Dyspnea	Respiratory, thoracic and mediastinal disorders	CTCAE (5.0)	Systematic Assessment		EG0000 events0 affected5 at risk EG0010 events0 affected4 at risk EG0021 events1 affected6 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	CTCAE (5.0)	Systematic Assessment		EG0000 events0 affected5 at risk EG0010 events0 affected4 at risk EG0021 events1 affected6 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	CTCAE (5.0)	Systematic Assessment		EG0000 events0 affected5 at risk EG0010 events0 affected4 at risk EG0021 events1 affected6 at risk
Rhinorrhea	Respiratory, thoracic and mediastinal disorders	CTCAE (5.0)	Systematic Assessment		EG0000 events0 affected5 at risk EG0010 events0 affected4 at risk EG0021 events1 affected6 at risk
Rash acneiform	Skin and subcutaneous tissue disorders	CTCAE (5.0)	Systematic Assessment		EG0001 events1 affected5 at risk EG0010 events0 affected4 at risk EG0020 events0 affected6 at risk
Skin ulceration	Skin and subcutaneous tissue disorders	CTCAE (5.0)	Systematic Assessment		EG0000 events0 affected5 at risk EG0011 events1 affected4 at risk EG0020 events0 affected6 at risk
Skin and subcutaneous tissue disorders-Other	Skin and subcutaneous tissue disorders	CTCAE (5.0)	Systematic Assessment	Squamous cell carcinoma	EG0000 events0 affected5 at risk EG0010 events0 affected4 at risk EG0021 events1 affected6 at risk
Hypertension	Vascular disorders	CTCAE (5.0)	Systematic Assessment		EG0000 events0 affected5 at risk EG0010 events0 affected4 at risk EG0022 events2 affected6 at risk
Hypotension	Vascular disorders	CTCAE (5.0)	Systematic Assessment		EG0001 events1 affected5 at risk EG0010 events0 affected4 at risk EG0020 events0 affected6 at risk
Thromboembolic event	Vascular disorders	CTCAE (5.0)	Systematic Assessment		EG0001 events1 affected5 at risk EG0010 events0 affected4 at risk EG0020 events0 affected6 at risk

ID	Term
D016908	Gram-Positive Bacterial Infections
D001424	Bacterial Infections
D001423	Bacterial Infections and Mycoses
D007239	Infections

ID	Term
D000890	Anti-Infective Agents
D045506	Therapeutic Uses
D020228	Pharmacologic Actions
D020164	Chemical Actions and Uses