An Open-label, Multi-center Clinical Trial of Eculizumab... | NCT01194973

Label	Type	Description	Intervention Names
Eculizumab	Experimental		Drug: Eculizumab

Name	Type	Description	Arm Group Labels	Other Names
Eculizumab	Drug	All patients received open-label eculizumab administered intravenously on the following dose schedule: Induction dose - 900 mg per week for four weeks and a dose of 1200 mg one week later; Maintenance dose - 1200 mg every two weeks. Patients who received plasma exchange or infusion during the eculizumab treatment period received a supplemental dose of 600 mg within one hour before plasma infusion or within one hour after the completion of each plasma exchange.

Measure	Description	Time Frame
Percentage of Patients With Complete TMA Response	Proportion of Patients with Complete TMA response was determined and defined by normalization of hematological parameters (platelet count and LDH) and preservation of renal function (defined as < 25% increase in serum creatinine from baseline) which were sustained for at least two consecutive measurements obtained at least four weeks apart.	Through 26 weeks
Percentage of Patients With Modified Complete TMA Response	Proportion of Patients with Modified Complete TMA response through 26 weeks of treatment was determined and defined by normalization of hematological parameters (platelet count and LDH) and improvement in renal function (defined as ≥ 25% reduction from the baseline value in serum creatinine, which were sustained for at least two consecutive measurements obtained at least four weeks apart.	Through 26 weeks

Measure	Description	Time Frame
Percentage of Patients With Complete Hematologic Response	Proportion of Patients with Complete Hematologic response through end of study was determined and defined by normalization of platelet count and LDH sustained for at least two consecutive measurements obtained at least four weeks apart.	Through 26 weeks

Eligibility Module

Eligibility Criteria

Inclusion:

Patient must be willing and able to give written informed consent.
Patient's age > 18 years.
Patients exhibit thrombocytopenia, hemolysis and elevated Serum Creatinine.
Patients with diagnosis of aHUS with or without an identified complement regulatory protein genetic abnormality or anti-complement factor antibody and for whom etiologies of hemolytic uremic syndrome have been ruled out as confirmed in the exclusion criteria
Female patients of childbearing potential must be practicing an effective, reliable and medically approved contraceptive regimen during the entire duration of the study, including the follow-up period. At the time of the last follow-up visit, patients must agree to continue to use adequate contraception methods for up to 5 months following discontinuation of eculizumab treatment.
Able and willing to comply with study procedures

Exclusion:

Chronic dialysis.
Prior eculizumab use or hypersensitivity to eculizumab, to murine proteins or to one of the excipients.
Known familial a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS-13) deficiency (ADAMTS-13 <5%).
Typical Hemolytic-Uremic Syndrome (HUS) (known Shiga toxin +).
History of malignancy within 5 years of screening.
Known human immunodeficiency virus (HIV) infection.
Identified drug exposure-related hemolytic-uremic syndrome (HUS).
Infection-related HUS.
HUS related to bone marrow transplant (BMT).
HUS related to vitamin B12 deficiency.
Known Systemic Lupus Erythematosus (SLE) or antiphospholipid antibody positivity or syndrome.
Patients with a confirmed diagnosis of sepsis defined as positive blood cultures within 7 days of the screening visit and not treated with antibiotics to which the organism is sensitive.
Presence or suspicion of active and untreated systemic bacterial infection that, in the opinion of the Investigator confounds an accurate diagnosis of aHUS or impedes the ability to manage the aHUS disease.
Pregnancy or lactation.
Unresolved systemic meningococcal disease.
Any medical or psychological condition that, in the opinion of the investigator, could increase the patient's risk by participating in the study or confound the outcome of the study.
Patients receiving chronic intravenous immunoglobulin (IVIg) within 8 weeks or chronic Rituximab therapy within 12 weeks of screening visit.
Patients receiving other immunosuppressive therapies such as steroids, mechanist target of rapamycin (mTOR) inhibitors, calcineurin inhibitors (e.g., cyclosporine or tacrolimus) are excluded unless: [1] part of an established post-transplant anti-rejection regime, or [2] patient has confirmed anti-Complement Factor Antibodies requiring immunosuppressive therapy, or [3] steroids are being used for a condition other than aHUS (example asthma).
Participation in any other investigational drug trial or device trial, or procedures beginning 4 weeks prior to screening and throughout the entire trial.

Facility	Status	City	State	ZIP	Country	Contacts
		Burlington	Massachusetts	01805	United States

PubMed Identifier	Type	Citation	Retractions
33783815	Derived	Pugh D, O'Sullivan ED, Duthie FA, Masson P, Kavanagh D. Interventions for atypical haemolytic uraemic syndrome. Cochrane Database Syst Rev. 2021 Mar 23;3(3):CD012862. doi: 10.1002/14651858.CD012862.pub2.
25833956	Derived	Cofiell R, Kukreja A, Bedard K, Yan Y, Mickle AP, Ogawa M, Bedrosian CL, Faas SJ. Eculizumab reduces complement activation, inflammation, endothelial damage, thrombosis, and renal injury markers in aHUS. Blood. 2015 May 21;125(21):3253-62. doi: 10.1182/blood-2014-09-600411. Epub 2015 Apr 1.

ID	Title	Description
FG000	Eculizumab	Eculizumab: All patients received open-label eculizumab administered intravenously on the following dose schedule: Induction dose - 900 mg per week for four weeks and a dose of 1200 mg one week later; Maintenance dose - 1200 mg every two weeks. Patients who received plasma exchange or infusion during the eculizumab treatment period received a supplemental dose of 600 mg within one hour before plasma infusion or within one hour after the completion of each plasma exchange.

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

Percentage of Patients With Complete TMA Response

Proportion of Patients with Complete TMA response was determined and defined by normalization of hematological parameters (platelet count and LDH) and preservation of renal function (defined as < 25% increase in serum creatinine from baseline) which were sustained for at least two consecutive measurements obtained at least four weeks apart.

The tabulations of the proportions of patients with Complete TMA Response through 26 weeks were performed for the ITT population. Exact binomial two-sided 95% CI using the Clopper-Pearson method for the responder rate was presented.

Posted

Number

95% Confidence Interval

Percentage of Participants

Through 26 weeks

ID	Title	Description
OG000	Eculizumab	Eculizumab: All patients received open-label eculizumab administered intravenously on the following dose schedule: Induction dose - 900 mg per week for four weeks and a dose of 1200 mg one week later; Maintenance dose - 1200 mg every two weeks. Patients who received plasma exchange or infusion during the eculizumab treatment period received a supplemental dose of 600 mg within one hour before plasma infusion or within one hour after the completion of each plasma exchange.

Units	Counts
Participants	OG00041

Title

Denominators

Categories

Title	Measurements
	OG00073.2(57.1 to 85.8)

Primary

Percentage of Patients With Modified Complete TMA Response

Proportion of Patients with Modified Complete TMA response through 26 weeks of treatment was determined and defined by normalization of hematological parameters (platelet count and LDH) and improvement in renal function (defined as ≥ 25% reduction from the baseline value in serum creatinine, which were sustained for at least two consecutive measurements obtained at least four weeks apart.

The tabulations of the proportions of patients with Modified Complete TMA Response through 26 weeks were performed for the ITT population. Exact binomial two-sided 95% CI using the Clopper-Pearson method for the responder rate was presented.

Posted

Number

95% Confidence Interval

Percentage of Participants

Through 26 weeks

ID	Title	Description
OG000	Eculizumab	Eculizumab: All patients received open-label eculizumab administered intravenously on the following dose schedule: Induction dose - 900 mg per week for four weeks and a dose of 1200 mg one week later; Maintenance dose - 1200 mg every two weeks. Patients who received plasma exchange or infusion during the eculizumab treatment period received a supplemental dose of 600 mg within one hour before plasma infusion or within one hour after the completion of each plasma exchange.

Units	Counts
Participants

Secondary

Percentage of Patients With Complete Hematologic Response

Proportion of Patients with Complete Hematologic response through end of study was determined and defined by normalization of platelet count and LDH sustained for at least two consecutive measurements obtained at least four weeks apart.

The tabulations of the proportions of patients with Complete Hematologic Response through 26 weeks were performed for the ITT population. The number of patients with response and responder rate, along with an exact two-sided 95% CI were summarized.

Posted

Number

95% Confidence Interval

Percentage of Participants

Through 26 weeks

ID	Title	Description
OG000	Eculizumab	Eculizumab: All patients received open-label eculizumab administered intravenously on the following dose schedule: Induction dose - 900 mg per week for four weeks and a dose of 1200 mg one week later; Maintenance dose - 1200 mg every two weeks. Patients who received plasma exchange or infusion during the eculizumab treatment period received a supplemental dose of 600 mg within one hour before plasma infusion or within one hour after the completion of each plasma exchange.

Units	Counts
Participants	OG000

Secondary

Percentage of Patients With Platelet Count Normalization

Proportion of Patients with Platelet Count Normalization through 26 weeks of treatment was determined and defined as the platelet count observed to be ≥ 150 x 109/L on at least two consecutive measurements which span a period of at least four weeks

The tabulations of the proportions of patients with Platelet Count Normalization through 26 weeks were performed for the ITT population. The number of patients with response and responder rate, along with an exact two-sided 95% CI were summarized.

Posted

Number

95% Confidence Interval

Percentage of Participants

Through 26 weeks

ID	Title	Description
OG000	Eculizumab	Eculizumab: All patients received open-label eculizumab administered intravenously on the following dose schedule: Induction dose - 900 mg per week for four weeks and a dose of 1200 mg one week later; Maintenance dose - 1200 mg every two weeks. Patients who received plasma exchange or infusion during the eculizumab treatment period received a supplemental dose of 600 mg within one hour before plasma infusion or within one hour after the completion of each plasma exchange.

Units	Counts
Participants

Secondary

Percentage of Patients With Estimated Glomerular Filtration Rate (eGFR) Improvement

Proportion of Patients with Estimated Glomerular Filtration Rate (eGFR) Improvement was determined and defined as an increase in eGFR by ≥ 15 mL/min/1.73m^2 from baseline, sustained for at least two consecutive measurements obtained at least four weeks apart.

The tabulations of the proportions of patients with Estimated Glomerular Filtration Rate (eGFR) Improvement through 26 weeks were performed for the ITT population. The number of patients with response and responder rate, along with an exact two-sided 95% CI were summarized.

Posted

Number

95% Confidence Interval

Percentage of Participants

Through 26 weeks

ID	Title	Description
OG000	Eculizumab	Eculizumab: All patients received open-label eculizumab administered intravenously on the following dose schedule: Induction dose - 900 mg per week for four weeks and a dose of 1200 mg one week later; Maintenance dose - 1200 mg every two weeks. Patients who received plasma exchange or infusion during the eculizumab treatment period received a supplemental dose of 600 mg within one hour before plasma infusion or within one hour after the completion of each plasma exchange.

Units	Counts
Participants

Secondary

Platelet Count Change From Baseline to 26 Weeks

Change from baseline platelet counts were analyzed for the ITT population using a repeated measures Analysis of variance (ANOVA) model. The estimated LS means of change from baseline at each post-baseline visit alongside with 95% CIs and P-values were calculated, as were the parameter estimates for the covariates and their associated P-values.

Posted

Least Squares Mean

95% Confidence Interval

10^9 cells/L

Through 26 weeks

ID	Title	Description
OG000	Eculizumab	Eculizumab: All patients received open-label eculizumab administered intravenously on the following dose schedule: Induction dose - 900 mg per week for four weeks and a dose of 1200 mg one week later; Maintenance dose - 1200 mg every two weeks. Patients who received plasma exchange or infusion during the eculizumab treatment period received a supplemental dose of 600 mg within one hour before plasma infusion or within one hour after the completion of each plasma exchange.

Units	Counts
Participants	OG000

Secondary

Percentage of Patients With Complete TMA Response

Proportion of Patients with Complete TMA response through end of study was determined and defined by normalization of hematological parameters (platelet count and LDH) and preservation of renal function (defined as < 25% increase in serum creatinine from baseline) which were sustained for at least two consecutive measurements obtained at least four weeks apart.

The tabulations of the proportions of patients with Complete TMA Response through end of study were performed for the ITT population. Exact binomial two-sided 95% CI using the Clopper-Pearson method for the responder rate was presented.

Posted

Number

95% Confidence Interval

Percentage of Participants

Through End of Study, Median Exposure 52 Weeks

ID	Title	Description
OG000	Eculizumab	Eculizumab: All patients received open-label eculizumab administered intravenously on the following dose schedule: Induction dose - 900 mg per week for four weeks and a dose of 1200 mg one week later; Maintenance dose - 1200 mg every two weeks. Patients who received plasma exchange or infusion during the eculizumab treatment period received a supplemental dose of 600 mg within one hour before plasma infusion or within one hour after the completion of each plasma exchange.

Units	Counts
Participants

Secondary

Percentage of Patients With Modified Complete TMA Response

Proportion of Patients with Modified Complete TMA response through end of study was determined and defined by normalization of hematological parameters (platelet count and LDH) and improvement in renal function (defined as ≥ 25% reduction from the baseline value in serum creatinine, which were sustained for at least two consecutive measurements obtained at least four weeks apart.

The tabulations of the proportions of patients with Modified Complete TMA Response through end of study were performed for the ITT population. Exact binomial two-sided 95% CI using the Clopper-Pearson method for the responder rate was presented.

Posted

Number

95% Confidence Interval

Percentage of Participants

Through End of Study, Median Exposure 52 Weeks

ID	Title	Description
OG000	Eculizumab	Eculizumab: All patients received open-label eculizumab administered intravenously on the following dose schedule: Induction dose - 900 mg per week for four weeks and a dose of 1200 mg one week later; Maintenance dose - 1200 mg every two weeks. Patients who received plasma exchange or infusion during the eculizumab treatment period received a supplemental dose of 600 mg within one hour before plasma infusion or within one hour after the completion of each plasma exchange.

Units	Counts
Participants

Secondary

Percentage of Patients With Complete Hematologic Response

Proportion of Patients with Complete Hematologic response through end of study of treatment was determined and defined by normalization of platelet count and LDH sustained for at least two consecutive measurements obtained at least four weeks apart.

The tabulations of the proportions of patients with Complete Hematologic Response through end of study were performed for the ITT population. The number of patients with response and responder rate, along with an exact two-sided 95% CI were summarized.

Posted

Number

95% Confidence Interval

Percentage of Participants

Through End of Study, Median Exposure 52 Weeks

ID	Title	Description
OG000	Eculizumab	Eculizumab: All patients received open-label eculizumab administered intravenously on the following dose schedule: Induction dose - 900 mg per week for four weeks and a dose of 1200 mg one week later; Maintenance dose - 1200 mg every two weeks. Patients who received plasma exchange or infusion during the eculizumab treatment period received a supplemental dose of 600 mg within one hour before plasma infusion or within one hour after the completion of each plasma exchange.

Units	Counts
Participants

Secondary

Percentage of Patients With Platelet Count Normalization

Proportion of Patients with Platelet Count Normalization through end of study of treatment was determined and defined as the platelet count observed to be ≥ 150 x 109/L on at least two consecutive measurements which span a period of at least four weeks

The tabulations of the proportions of patients with Platelet Count Normalization through end of study were performed for the ITT population. The number of patients with response and responder rate, along with an exact two-sided 95% CI were summarized.

Posted

Number

95% Confidence Interval

Percentage of Participants

Through End of Study, Median Exposure 52 Weeks

ID	Title	Description
OG000	Eculizumab	Eculizumab: All patients received open-label eculizumab administered intravenously on the following dose schedule: Induction dose - 900 mg per week for four weeks and a dose of 1200 mg one week later; Maintenance dose - 1200 mg every two weeks. Patients who received plasma exchange or infusion during the eculizumab treatment period received a supplemental dose of 600 mg within one hour before plasma infusion or within one hour after the completion of each plasma exchange.

Units	Counts
Participants

Secondary

Percentage of Patients With Estimated Glomerular Filtration Rate (eGFR) Improvement

Proportion of Patients with Estimated Glomerular Filtration Rate (eGFR) Improvement was determined and defined as an increase in eGFR by ≥ 15 mL/min/1.73m^2 from baseline sustained for at least two consecutive measurements obtained at least four weeks apart

The tabulations of the proportions of patients with Estimated Glomerular Filtration Rate (eGFR) Improvement through end of study were performed for the ITT population. The number of patients with response and responder rate, along with an exact two-sided 95% CI were summarized for each parameter.

Posted

Number

95% Confidence Interval

Percentage of Participants

Through End of Study, Median Exposure 52 Weeks

ID	Title	Description
OG000	Eculizumab	Eculizumab: All patients received open-label eculizumab administered intravenously on the following dose schedule: Induction dose - 900 mg per week for four weeks and a dose of 1200 mg one week later; Maintenance dose - 1200 mg every two weeks. Patients who received plasma exchange or infusion during the eculizumab treatment period received a supplemental dose of 600 mg within one hour before plasma infusion or within one hour after the completion of each plasma exchange.

Units	Counts
Participants

Secondary

Platelet Count Change From Baseline to 52 Weeks

Change from baseline platelet counts were analyzed for the ITT population using a repeated measures ANOVA model. The estimated LS means of change from baseline at each post-baseline visit alongside with 95% CIs and P-values were calculated, as were the parameter estimates for the covariates and their associated P-values.

Posted

Least Squares Mean

95% Confidence Interval

10^9 cells/L

Through 52 Weeks

ID	Title	Description
OG000	Eculizumab	Eculizumab: All patients received open-label eculizumab administered intravenously on the following dose schedule: Induction dose - 900 mg per week for four weeks and a dose of 1200 mg one week later; Maintenance dose - 1200 mg every two weeks. Patients who received plasma exchange or infusion during the eculizumab treatment period received a supplemental dose of 600 mg within one hour before plasma infusion or within one hour after the completion of each plasma exchange.

Units	Counts
Participants	OG000

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Haemolytic uraemic syndrome	Blood and lymphatic system disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
Thrombotic microangiopathy	Blood and lymphatic system disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
Medical device complication	General disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
Kidney transplant rejection	Immune system disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
Bronchitis	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
Device related infection	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
Device related sepsis	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0002 affected41 at risk
Genitourinary tract gonococcal infection	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
Meningitis meningococcal	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
Meningococcal sepsis	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
Pneumonia	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
Pyelonephritis	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0002 affected41 at risk
Shunt infection	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
Shunt malfunction	Injury, poisoning and procedural complications	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
Convulsion	Nervous system disorders	MedDRA Version 15.1	Systematic Assessment	EG0002 affected41 at risk
Haemorrhage intracranial	Nervous system disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
Paraesthesia	Nervous system disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
Posterior reversible encephalopathy syndrome	Nervous system disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
Renal failure acute	Renal and urinary disorders	MedDRA Version 15.1	Systematic Assessment	EG0002 affected41 at risk
Renal failure chronic	Renal and urinary disorders	MedDRA Version 15.1	Systematic Assessment	EG0002 affected41 at risk
Renal impairment	Renal and urinary disorders	MedDRA Version 15.1	Systematic Assessment	EG0002 affected41 at risk
Renal vessel disorder	Renal and urinary disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA Version 15.1	Systematic Assessment	EG0002 affected41 at risk
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA Version 15.1	Systematic Assessment	EG0002 affected41 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
Rash papular	Skin and subcutaneous tissue disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
Skin necrosis	Skin and subcutaneous tissue disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
Hypertension	Vascular disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
Hypertensive crisis	Vascular disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
Venous thrombosis	Vascular disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
Hypoglycemia	Metabolism and nutrition disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
ANAEMIA	Blood and lymphatic system disorders	MedDRA Version 15.1	Systematic Assessment	EG0007 affected41 at risk
EOSINOPHILIA	Blood and lymphatic system disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
IRON DEFICIENCY ANAEMIA	Blood and lymphatic system disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
LEUKOPENIA	Blood and lymphatic system disorders	MedDRA Version 15.1	Systematic Assessment	EG0005 affected41 at risk
LYMPHOPENIA	Blood and lymphatic system disorders	MedDRA Version 15.1	Systematic Assessment	EG0003 affected41 at risk
NEUTROPENIA	Blood and lymphatic system disorders	MedDRA Version 15.1	Systematic Assessment	EG0002 affected41 at risk
SPONTANEOUS HAEMATOMA	Blood and lymphatic system disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
THROMBOCYTOPENIA	Blood and lymphatic system disorders	MedDRA Version 15.1	Systematic Assessment	EG0002 affected41 at risk
ANGINA PECTORIS	Cardiac disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
CARDIOMYOPATHY	Cardiac disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
PALPITATIONS	Cardiac disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
TACHYCARDIA	Cardiac disorders	MedDRA Version 15.1	Systematic Assessment	EG0002 affected41 at risk
EAR PAIN	Ear and labyrinth disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
TINNITUS	Ear and labyrinth disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
TYMPANIC MEMBRANE PERFORATION	Ear and labyrinth disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
VERTIGO	Ear and labyrinth disorders	MedDRA Version 15.1	Systematic Assessment	EG0003 affected41 at risk
HYPERPARATHYROIDISM	Endocrine disorders	MedDRA Version 15.1	Systematic Assessment	EG0002 affected41 at risk
CONJUNCTIVAL HAEMORRHAGE	Eye disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
CONJUNCTIVITIS	Eye disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
EYE INFLAMMATION	Eye disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
LACRIMATION INCREASED	Eye disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
RETINOPATHY HYPERTENSIVE	Eye disorders	MedDRA Version 15.1	Systematic Assessment	EG0002 affected41 at risk
UVEITIS	Eye disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
VISION BLURRED	Eye disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
ABDOMINAL DISCOMFORT	Gastrointestinal disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
ABDOMINAL PAIN	Gastrointestinal disorders	MedDRA Version 15.1	Systematic Assessment	EG0003 affected41 at risk
ABDOMINAL PAIN UPPER	Gastrointestinal disorders	MedDRA Version 15.1	Systematic Assessment	EG0002 affected41 at risk
CONSTIPATION	Gastrointestinal disorders	MedDRA Version 15.1	Systematic Assessment	EG0003 affected41 at risk
DIARRHOEA	Gastrointestinal disorders	MedDRA Version 15.1	Systematic Assessment	EG00013 affected41 at risk
DRY MOUTH	Gastrointestinal disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
DYSPEPSIA	Gastrointestinal disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
DYSPHAGIA	Gastrointestinal disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
ENTERITIS	Gastrointestinal disorders	MedDRA Version 15.1	Systematic Assessment	EG0002 affected41 at risk
GASTROINTESTINAL DISORDER	Gastrointestinal disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
GASTROINTESTINAL PAIN	Gastrointestinal disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
GASTROOESOPHAGEAL REFLUX DISEASE	Gastrointestinal disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
GINGIVAL HYPERTROPHY	Gastrointestinal disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
MOUTH ULCERATION	Gastrointestinal disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
NAUSEA	Gastrointestinal disorders	MedDRA Version 15.1	Systematic Assessment	EG0005 affected41 at risk
ODYNOPHAGIA	Gastrointestinal disorders	MedDRA Version 15.1	Systematic Assessment	EG0002 affected41 at risk
STOMATITIS	Gastrointestinal disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
VOMITING	Gastrointestinal disorders	MedDRA Version 15.1	Systematic Assessment	EG0006 affected41 at risk
ASTHENIA	General disorders	MedDRA Version 15.1	Systematic Assessment	EG0006 affected41 at risk
CALCINOSIS	General disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
CATHETER SITE DISCHARGE	General disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
CATHETER SITE ERYTHEMA	General disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
CATHETER SITE PRURITUS	General disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
CHEST DISCOMFORT	General disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
CHEST PAIN	General disorders	MedDRA Version 15.1	Systematic Assessment	EG0002 affected41 at risk
CHILLS	General disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
DEVICE OCCLUSION	General disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
FATIGUE	General disorders	MedDRA Version 15.1	Systematic Assessment	EG0003 affected41 at risk
IMPAIRED HEALING	General disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
INFLUENZA LIKE ILLNESS	General disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
MALAISE	General disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
MEDICAL DEVICE COMPLICATION	General disorders	MedDRA Version 15.1	Systematic Assessment	EG0002 affected41 at risk
OEDEMA	General disorders	MedDRA Version 15.1	Systematic Assessment	EG0002 affected41 at risk
OEDEMA PERIPHERAL	General disorders	MedDRA Version 15.1	Systematic Assessment	EG0009 affected41 at risk
PYREXIA	General disorders	MedDRA Version 15.1	Systematic Assessment	EG0007 affected41 at risk
CHOLECYSTITIS	Hepatobiliary disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
CHOLELITHIASIS	Hepatobiliary disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
CHOLESTASIS	Hepatobiliary disorders	MedDRA Version 15.1	Systematic Assessment	EG0002 affected41 at risk
HEPATOCELLULAR INJURY	Hepatobiliary disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
ASYMPTOMATIC BACTERIURIA	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
BACTERIAL INFECTION	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
BACTERIURIA	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
BK VIRUS INFECTION	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
BRONCHITIS	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0005 affected41 at risk
BRONCHITIS VIRAL	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
CATHETER SITE INFECTION	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
CYSTITIS	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
DENTAL GANGRENE	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
DEVICE RELATED INFECTION	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
DEVICE RELATED SEPSIS	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
EAR INFECTION	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
ERYSIPELAS	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
FOLLICULITIS	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
GASTROENTERITIS	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0003 affected41 at risk
GENITAL INFECTION FUNGAL	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
HERPES ZOSTER	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
INFECTION	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
INFLUENZA	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0002 affected41 at risk
LARYNGITIS	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
LUNG INFECTION	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
LYMPHANGITIS	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
NASOPHARYNGITIS	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0008 affected41 at risk
ONYCHOMYCOSIS	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
ORAL FUNGAL INFECTION	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
ORAL HERPES	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0003 affected41 at risk
OTITIS MEDIA	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
PHARYNGITIS	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
PULMONARY SEPSIS	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
PYELONEPHRITIS	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
RESPIRATORY TRACT INFECTION	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
RHINITIS	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0003 affected41 at risk
SINUSITIS	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0002 affected41 at risk
STAPHYLOCOCCAL INFECTION	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0002 affected41 at risk
TINEA PEDIS	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
UPPER RESPIRATORY TRACT INFECTION	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
URINARY TRACT INFECTION	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0007 affected41 at risk
VAGINITIS BACTERIAL	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
VIRAL INFECTION	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0002 affected41 at risk
ARTERIOVENOUS FISTULA SITE COMPLICATION	Injury, poisoning and procedural complications	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
CONTUSION	Injury, poisoning and procedural complications	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
FOOT FRACTURE	Injury, poisoning and procedural complications	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
INFUSION RELATED REACTION	Injury, poisoning and procedural complications	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
PROCEDURAL COMPLICATION	Injury, poisoning and procedural complications	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
SHUNT MALFUNCTION	Injury, poisoning and procedural complications	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
SKELETAL INJURY	Injury, poisoning and procedural complications	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
UPPER LIMB FRACTURE	Injury, poisoning and procedural complications	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
WOUND	Injury, poisoning and procedural complications	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
BLOOD PRESSURE INCREASED	Investigations	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
CARDIAC MURMUR	Investigations	MedDRA Version 15.1	Systematic Assessment	EG0002 affected41 at risk
EOSINOPHIL COUNT INCREASED	Investigations	MedDRA Version 15.1	Systematic Assessment	EG0002 affected41 at risk
FREE HAEMOGLOBIN PRESENT	Investigations	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
LIVER FUNCTION TEST ABNORMAL	Investigations	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
PLATELET COUNT DECREASED	Investigations	MedDRA Version 15.1	Systematic Assessment	EG0002 affected41 at risk
URINE PROTEIN/CREATININE RATIO INCREASED	Investigations	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
WEIGHT DECREASED	Investigations	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
WHITE BLOOD CELL COUNT INCREASED	Investigations	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
ACIDOSIS	Metabolism and nutrition disorders	MedDRA Version 15.1	Systematic Assessment	EG0002 affected41 at risk
DECREASED APPETITE	Metabolism and nutrition disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
DEHYDRATION	Metabolism and nutrition disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
ELECTROLYTE IMBALANCE	Metabolism and nutrition disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
HYPERCALCAEMIA	Metabolism and nutrition disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
HYPERCREATININAEMIA	Metabolism and nutrition disorders	MedDRA Version 15.1	Systematic Assessment	EG0002 affected41 at risk
HYPERKALAEMIA	Metabolism and nutrition disorders	MedDRA Version 15.1	Systematic Assessment	EG0004 affected41 at risk
HYPERPHOSPHATAEMIA	Metabolism and nutrition disorders	MedDRA Version 15.1	Systematic Assessment	EG0005 affected41 at risk
HYPERURICAEMIA	Metabolism and nutrition disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
HYPERVOLAEMIA	Metabolism and nutrition disorders	MedDRA Version 15.1	Systematic Assessment	EG0002 affected41 at risk
HYPOCALCAEMIA	Metabolism and nutrition disorders	MedDRA Version 15.1	Systematic Assessment	EG0003 affected41 at risk
HYPOGLYCAEMIA	Metabolism and nutrition disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
HYPOKALAEMIA	Metabolism and nutrition disorders	MedDRA Version 15.1	Systematic Assessment	EG0004 affected41 at risk
HYPOMAGNESAEMIA	Metabolism and nutrition disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
HYPOPHOSPHATAEMIA	Metabolism and nutrition disorders	MedDRA Version 15.1	Systematic Assessment	EG0004 affected41 at risk
IRON DEFICIENCY	Metabolism and nutrition disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
METABOLIC ACIDOSIS	Metabolism and nutrition disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
OVERWEIGHT	Metabolism and nutrition disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
TYPE 2 DIABETES MELLITUS	Metabolism and nutrition disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
VITAMIN D DEFICIENCY	Metabolism and nutrition disorders	MedDRA Version 15.1	Systematic Assessment	EG0004 affected41 at risk
ARTHRALGIA	Musculoskeletal and connective tissue disorders	MedDRA Version 15.1	Systematic Assessment	EG0008 affected41 at risk
BACK PAIN	Musculoskeletal and connective tissue disorders	MedDRA Version 15.1	Systematic Assessment	EG0003 affected41 at risk
BONE PAIN	Musculoskeletal and connective tissue disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
CHONDROCALCINOSIS	Musculoskeletal and connective tissue disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
HAEMARTHROSIS	Musculoskeletal and connective tissue disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
JOINT EFFUSION	Musculoskeletal and connective tissue disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
JOINT STIFFNESS	Musculoskeletal and connective tissue disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
MUSCLE SPASMS	Musculoskeletal and connective tissue disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
MUSCULOSKELETAL PAIN	Musculoskeletal and connective tissue disorders	MedDRA Version 15.1	Systematic Assessment	EG0002 affected41 at risk
MYALGIA	Musculoskeletal and connective tissue disorders	MedDRA Version 15.1	Systematic Assessment	EG0004 affected41 at risk
NECK PAIN	Musculoskeletal and connective tissue disorders	MedDRA Version 15.1	Systematic Assessment	EG0002 affected41 at risk
OSTEOPENIA	Musculoskeletal and connective tissue disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
PAIN IN EXTREMITY	Musculoskeletal and connective tissue disorders	MedDRA Version 15.1	Systematic Assessment	EG0002 affected41 at risk
RHABDOMYOLYSIS	Musculoskeletal and connective tissue disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
PARATHYROID TUMOUR BENIGN	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
AMNESIA	Nervous system disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
DIZZINESS	Nervous system disorders	MedDRA Version 15.1	Systematic Assessment	EG0002 affected41 at risk
HEADACHE	Nervous system disorders	MedDRA Version 15.1	Systematic Assessment	EG00015 affected41 at risk
LOSS OF CONSCIOUSNESS	Nervous system disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
MIGRAINE	Nervous system disorders	MedDRA Version 15.1	Systematic Assessment	EG0002 affected41 at risk
PARAESTHESIA	Nervous system disorders	MedDRA Version 15.1	Systematic Assessment	EG0003 affected41 at risk
POLYNEUROPATHY	Nervous system disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
PRESYNCOPE	Nervous system disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
SCIATICA	Nervous system disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
SYNCOPE	Nervous system disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
TREMOR	Nervous system disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
AGITATION	Psychiatric disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
ANXIETY	Psychiatric disorders	MedDRA Version 15.1	Systematic Assessment	EG0004 affected41 at risk
DEPRESSED MOOD	Psychiatric disorders	MedDRA Version 15.1	Systematic Assessment	EG0002 affected41 at risk
DEPRESSION	Psychiatric disorders	MedDRA Version 15.1	Systematic Assessment	EG0003 affected41 at risk
INSOMNIA	Psychiatric disorders	MedDRA Version 15.1	Systematic Assessment	EG0005 affected41 at risk
NIGHTMARE	Psychiatric disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
ANURIA	Renal and urinary disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
DYSURIA	Renal and urinary disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
HAEMATURIA	Renal and urinary disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
PROTEINURIA	Renal and urinary disorders	MedDRA Version 15.1	Systematic Assessment	EG0005 affected41 at risk
RENAL FAILURE ACUTE	Renal and urinary disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
RENAL FAILURE CHRONIC	Renal and urinary disorders	MedDRA Version 15.1	Systematic Assessment	EG0002 affected41 at risk
RENAL IMPAIRMENT	Renal and urinary disorders	MedDRA Version 15.1	Systematic Assessment	EG0006 affected41 at risk
RENAL VESSEL DISORDER	Renal and urinary disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
TUBULOINTERSTITIAL NEPHRITIS	Renal and urinary disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
URINE ABNORMALITY	Renal and urinary disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
VESICOURETERIC REFLUX	Renal and urinary disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
AMENORRHOEA	Reproductive system and breast disorders	MedDRA Version 15.1	Systematic Assessment	EG0002 affected41 at risk
ATROPHIC VULVOVAGINITIS	Reproductive system and breast disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
BREAST CYST	Reproductive system and breast disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
DYSMENORRHOEA	Reproductive system and breast disorders	MedDRA Version 15.1	Systematic Assessment	EG0002 affected41 at risk
ENDOMETRIOSIS	Reproductive system and breast disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
HAEMATOSPERMIA	Reproductive system and breast disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
METRORRHAGIA	Reproductive system and breast disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
COUGH	Respiratory, thoracic and mediastinal disorders	MedDRA Version 15.1	Systematic Assessment	EG0007 affected41 at risk
DYSPNOEA	Respiratory, thoracic and mediastinal disorders	MedDRA Version 15.1	Systematic Assessment	EG0005 affected41 at risk
DYSPNOEA EXERTIONAL	Respiratory, thoracic and mediastinal disorders	MedDRA Version 15.1	Systematic Assessment	EG0002 affected41 at risk
EPISTAXIS	Respiratory, thoracic and mediastinal disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
NASAL SEPTUM DEVIATION	Respiratory, thoracic and mediastinal disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
OROPHARYNGEAL PAIN	Respiratory, thoracic and mediastinal disorders	MedDRA Version 15.1	Systematic Assessment	EG0003 affected41 at risk
PLEURAL EFFUSION	Respiratory, thoracic and mediastinal disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
PRODUCTIVE COUGH	Respiratory, thoracic and mediastinal disorders	MedDRA Version 15.1	Systematic Assessment	EG0002 affected41 at risk
PULMONARY CONGESTION	Respiratory, thoracic and mediastinal disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
PULMONARY OEDEMA	Respiratory, thoracic and mediastinal disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
RHINITIS ALLERGIC	Respiratory, thoracic and mediastinal disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
RHINORRHOEA	Respiratory, thoracic and mediastinal disorders	MedDRA Version 15.1	Systematic Assessment	EG0002 affected41 at risk
SNORING	Respiratory, thoracic and mediastinal disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
WHEEZING	Respiratory, thoracic and mediastinal disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
ALOPECIA	Skin and subcutaneous tissue disorders	MedDRA Version 15.1	Systematic Assessment	EG0005 affected41 at risk
DERMATITIS	Skin and subcutaneous tissue disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
ECZEMA	Skin and subcutaneous tissue disorders	MedDRA Version 15.1	Systematic Assessment	EG0002 affected41 at risk
ERYTHEMA	Skin and subcutaneous tissue disorders	MedDRA Version 15.1	Systematic Assessment	EG0002 affected41 at risk
INTERTRIGO	Skin and subcutaneous tissue disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
NIGHT SWEATS	Skin and subcutaneous tissue disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
PETECHIAE	Skin and subcutaneous tissue disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
PHOTOSENSITIVITY REACTION	Skin and subcutaneous tissue disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
PRURITUS	Skin and subcutaneous tissue disorders	MedDRA Version 15.1	Systematic Assessment	EG0004 affected41 at risk
PURPURA	Skin and subcutaneous tissue disorders	MedDRA Version 15.1	Systematic Assessment	EG0002 affected41 at risk
RASH	Skin and subcutaneous tissue disorders	MedDRA Version 15.1	Systematic Assessment	EG0004 affected41 at risk
RASH ERYTHEMATOUS	Skin and subcutaneous tissue disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
RASH PRURITIC	Skin and subcutaneous tissue disorders	MedDRA Version 15.1	Systematic Assessment	EG0002 affected41 at risk
SKIN DISCOLOURATION	Skin and subcutaneous tissue disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
URTICARIA	Skin and subcutaneous tissue disorders	MedDRA Version 15.1	Systematic Assessment	EG0002 affected41 at risk
DEEP VEIN THROMBOSIS	Vascular disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
HAEMATOMA	Vascular disorders	MedDRA Version 15.1	Systematic Assessment	EG0003 affected41 at risk
HOT FLUSH	Vascular disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
HYPERTENSION	Vascular disorders	MedDRA Version 15.1	Systematic Assessment	EG0005 affected41 at risk
HYPOTENSION	Vascular disorders	MedDRA Version 15.1	Systematic Assessment	EG0007 affected41 at risk
STEAL SYNDROME	Vascular disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
THROMBOPHLEBITIS	Vascular disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk
VENOUS THROMBOSIS	Vascular disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected41 at risk

ID	Term
D006463	Hemolytic-Uremic Syndrome
D014511	Uremia
D007674	Kidney Diseases
D014570	Urologic Diseases
D052776	Female Urogenital Diseases
D005261	Female Urogenital Diseases and Pregnancy Complications
D000091642	Urogenital Diseases
D052801	Male Urogenital Diseases
D000743	Anemia, Hemolytic
D000740	Anemia
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases
D057049	Thrombotic Microangiopathies
D013921	Thrombocytopenia
D001791	Blood Platelet Disorders
D000095542	Cytopenia