A Prospective, Open Label Study Evaluating Two Management... | NCT01493557

NCT01493557

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Pradaxa (dabigaran etexilate)	Other	Patients with non valvular atrial fibrillation for whom Pradaxa is indicated in accordance with the current local label, not previously treated with Pradaxa, will be provided 3 months of treatment for the prevention of stroke and systemic embolism. Patients who report gastrointestinal symptoms (GIS) will be randomized to one of two management strategies, and data documenting the intensity and duration of the GIS will be collected.	Drug: Pradaxa (dabigatran etexilate)
Pradaxa and pantoprazole	Active Comparator	Patients that develop gastrointestinal symptoms (GIS) will be randomized 1:1 to either pantoprazole 40 mg q.a.m., p.o., or taking Pradaxa (dabigatran etexilate) within 30 minutes after a meal	Drug: pantoprazole Drug: Pradaxa (dabigatran etexilate)
Pradaxa, 30 minutes after a meal	Active Comparator	Patients that develop gastrointestinal symptoms (GIS) will be randomized 1:1 to either pantoprazole 40 mg q.a.m., p.o., or taking Pradaxa (dabigatran etexilate) within 30 minutes after a meal	Drug: Pradaxa, within 30 minutes after a meal

Name	Type	Description	Arm Group Labels	Other Names
pantoprazole	Drug	40 mg q.a.m, p.o.	Pradaxa and pantoprazole
Pradaxa (dabigatran etexilate)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
The Rate of Complete Effectiveness of Initial GIS Management Strategy	The percentage of patients experiencing complete relief of gastrointestinal symptoms (GIS) when taking pantoprazole 40 mg once daily in the morning (q.a.m.) vs. administration of Pradaxa® (dabigatran etexilate) within 30 minutes after a meal at 4 weeks. Complete effectiveness is defined as at the time of evaluation, both primary GIS and secondary GIS are all resolved.	Week 4

Secondary Outcomes

Measure	Description	Time Frame
Rate of Partial Effectiveness of Initial GIS Management Strategies	The percentage of patients experiencing partial relief of gastrointestinal symptoms (GIS) when taking pantoprazole 40 mg once daily in the morning (q.a.m.) and patients taking Pradaxa® (dabigatran etexilate) within 30 minutes after a meal at 4 weeks. Partial effectiveness is defined as at the time of evaluation, either primary GIS is improved; or primary GIS is resolved, but there were still un-resolved secondary GIS.

Eligibility Module

Eligibility Criteria

Inclusion criteria:

Documented non-valvular atrial fibrillation (NVAF) for whom Pradaxa® (dabigatran etexilate) is indicated per the current local label, but who have not received treatment with Pradaxa® (dabigatran etexilate), or who have not been started on Pradaxa® (dabigatran etexilate) more than 7 days prior to potential enrolment in the study. NVAF may be documented by 12-lead electrocardiogram, rhythm strip, pacemaker/ implantable cardioverter defibrillator (ICD) electrograms or Holter monitoring
Male and female patients, age greater than or equal to 18 years at entry
Written, informed consent

Exclusion criteria:

History within 2 weeks of any of the following gastrointestinal (GI) disorders: heartburn, indigestion, gastritis, upper abdominal pain or discomfort, or gastroesophageal reflux requiring the use of proton pump inhibitors, histamine-2 receptor blockers or antacids. Patients with nausea and/or vomiting within the 2 weeks are not excluded if the symptoms were clearly associated with a self-limited acute or febrile illness. Short-term use of PPIs, as prophylaxis, in a hospital setting for the prevention of stress ulcers is acceptable. Calcium carbonate supplements for calcium replacement is not exclusionary (as long as these products are being used as calcium supplementation/replacement and are not being used to treat or relieve GIS.)
GI bleeding within one year or any history of symptomatic or endoscopically documented gastroduodenal ulcer or diverticulitis, unless the cause has been permanently eliminated by medical therapy or by surgery(e.g., patients with peptic ulcer disease with endoscopically proven cure after therapy or lower GI bleeding due to diverticulosis cured by segmental colectomy are not excluded.)
not applicable
Contraindication to pantoprazole or other proton pump inhibitors, e.g. omeprazole, lansoprazole, rabeprazole, atnoprazole, esomeprazole
Contraindication to Pradaxa® (dabigatran etexilate) or known hypersensitivity to Pradaxa® (dabigatran etexilate) or its excipients
Hemorrhagic disorder, bleeding diathesis or active pathological bleeding
Need for anticoagulant treatment for disorders other than atrial fibrillation
Current treatment with rifampin
Creatinine clearance <15ml/min (in Canada, <30ml/min), or patients on renal replacement therapy (dialysis)
Pre-menopausal women (last menstruation less than or equal to 1 year prior to informed consent) who: are nursing or pregnant, or are of child bearing potential and are not practicing an acceptable method of birth control, or do not plan to continue using this method throughout the study. Acceptable methods of birth control include abstinence, tubal ligation, transdermal patch, intra uterine devices/systems (IUDs/IUSs), oral implantable or injectable contraceptives, double barrier method and vasectomized partner.
Patients who have received an investigational drug in the past 30 days or are participating in another drug study
Patients considered unreliable by the investigator concerning the requirements for follow-up during the study
Any condition the investigator believes would not allow safe participation in the study
Contraindication in patients with mechanical heart valves. The use of Pradaxa in the setting of other forms of valvular heart disease, including the presence of a bio-prosthetic valve, is not recommended.

Name	Affiliation	Role
Boehringer Ingelheim	Boehringer Ingelheim	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
1160.128.1046 Boehringer Ingelheim Investigational Site		Birmingham	Alabama		United States
1160.128.1045 Boehringer Ingelheim Investigational Site

PubMed Identifier	Type	Citation	Retractions
27709460	Derived	O'Dea D, Whetteckey J, Ting N. A Prospective, Randomized, Open-Label Study to Evaluate Two Management Strategies for Gastrointestinal Symptoms in Patients Newly on Treatment with Dabigatran. Cardiol Ther. 2016 Dec;5(2):187-201. doi: 10.1007/s40119-016-0071-5. Epub 2016 Oct 5.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Pradaxa, 30 Minutes After a Meal (Randomized)	Randomized patients that develop gastrointestinal symptoms (GIS) were orally administered to Pradaxa (dabigatran etexilate) 150 mg or Pradaxa (dabigatran etexilate) 75 mg twice daily ( b.i.d.) taken with food (150 mg or 110 mg b.i.d. in Canada), within 30 minutes after a meal (4 weeks).

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Pradaxa, 30 Minutes After a Meal (Randomized)	Randomized patients that develop gastrointestinal symptoms (GIS) were orally administered to Pradaxa (dabigatran etexilate) 150 mg or Pradaxa (dabigatran etexilate) 75 mg twice daily ( b.i.d.) taken with food (150 mg or 110 mg b.i.d. in Canada), within 30 minutes after a meal (4 weeks).
BG001	Pantoprazole 40 mg (Randomized)	Randomized patients that develop gastrointestinal symptoms (GIS) were orally administered to delayed release tablet pantoprazole 40 mg once daily in the Morning (q.a.m) (4 weeks).
BG002	Pradaxa, Never Randomized	Patients who were treated for 3 months with Pradaxa ® and were never randomized to management strategies.
BG003	Total	Total of all reporting groups

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

The Rate of Complete Effectiveness of Initial GIS Management Strategy

The percentage of patients experiencing complete relief of gastrointestinal symptoms (GIS) when taking pantoprazole 40 mg once daily in the morning (q.a.m.) vs. administration of Pradaxa® (dabigatran etexilate) within 30 minutes after a meal at 4 weeks.

Complete effectiveness is defined as at the time of evaluation, both primary GIS and secondary GIS are all resolved.

Full Analysis Set (FAS): This patient set included all patients who developed GIS and who were randomized into the two management strategies.

Posted

Number

percentage of participants

Week 4

ID	Title	Description
OG000	Pradaxa, 30 Minutes After a Meal (Randomized)	Randomized patients that develop gastrointestinal symptoms (GIS) were orally administered to Pradaxa (dabigatran etexilate) 150 mg or Pradaxa (dabigatran etexilate) 75 mg twice daily ( b.i.d.) taken with food (150 mg or 110 mg b.i.d. in Canada), within 30 minutes after a meal (4 weeks).
OG001	Pantoprazole 40 mg (Randomized)	Randomized patients that develop gastrointestinal symptoms (GIS) were orally administered to delayed release tablet pantoprazole 40 mg once daily in the Morning (q.a.m) (4 weeks).

Units	Counts
Participants	OG00059 OG00158

Title

Denominators

Categories

Title	Measurements
	OG00055.9 OG00167.2

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Evaluation of GIS was based on Last observation carried forward (LOCF) data up to the last observed time or up to adding the second management strategy.	Fisher Exact		0.2554		Mean Difference (Final Values)	11.31			2-Sided	95	-6.54	29.49			Exact 95% Confidence interval (CI) and the difference between the two strategies were calculated using the Clopper Pearson approach.	No	Superiority or Other

Secondary

Rate of Partial Effectiveness of Initial GIS Management Strategies

The percentage of patients experiencing partial relief of gastrointestinal symptoms (GIS) when taking pantoprazole 40 mg once daily in the morning (q.a.m.) and patients taking Pradaxa® (dabigatran etexilate) within 30 minutes after a meal at 4 weeks.

Partial effectiveness is defined as at the time of evaluation, either primary GIS is improved; or primary GIS is resolved, but there were still un-resolved secondary GIS.

Full Analysis Set (FAS)

Posted

Number

percentage of participants

Week 4

ID	Title	Description
OG000	Pradaxa, 30 Minutes After a Meal (Randomized)	Randomized patients that develop gastrointestinal symptoms (GIS) were orally administered to Pradaxa (dabigatran etexilate) 150 mg or Pradaxa (dabigatran etexilate) 75 mg twice daily ( b.i.d.) taken with food (150 mg or 110 mg b.i.d. in Canada), within 30 minutes after a meal (4 weeks).
OG001	Pantoprazole 40 mg (Randomized)	Randomized patients that develop gastrointestinal symptoms (GIS) were orally administered to delayed release tablet pantoprazole 40 mg once daily in the Morning (q.a.m) (4 weeks).

Units	Counts

Secondary

Combined Rate of Complete or Partial Effectiveness of Initial GIS Management Strategies

The percentage of patients experiencing complete or partial effectiveness of gastrointestinal symptoms (GIS) when taking pantoprazole 40 mg once daily in the morning (q.a.m.) vs. administration of Pradaxa ® (dabigatran etexilate) within 30 minutes after a meal at 4 weeks.

Complete effectiveness is defined as at the time of evaluation, both primary GIS and secondary GIS are all resolved. Partial effectiveness is defined as at the time of evaluation, either primary GIS is improved; or primary GIS is resolved, but there were still un-resolved secondary GIS.

Full Analysis Set (FAS)

Posted

Number

percentage of participants

Week 4

ID	Title	Description
OG000	Pradaxa, 30 Minutes After a Meal (Randomized)	Randomized patients that develop gastrointestinal symptoms (GIS) were orally administered to Pradaxa (dabigatran etexilate) 150 mg or Pradaxa (dabigatran etexilate) 75 mg twice daily ( b.i.d.) taken with food (150 mg or 110 mg b.i.d. in Canada), within 30 minutes after a meal (4 weeks).
OG001	Pantoprazole 40 mg (Randomized)	Randomized patients that develop gastrointestinal symptoms (GIS) were orally administered to delayed release tablet pantoprazole 40 mg once daily in the Morning (q.a.m) (4 weeks).

Secondary

Rate of Complete Effectiveness of Combined GIS Management Strategies

The percentage of patients experiencing complete relief of combined gastrointestinal symptoms (GIS) when taking pantoprazole 40 mg once daily in the morning (q.a.m.) vs. administration of Pradaxa ® (dabigatran etexilate) within 30 minutes after a meal.

Complete effectiveness is defined as at the time of evaluation, both primary GIS and secondary GIS are all resolved.

Full Analysis Set (FAS)

Posted

Number

percentage of participants

Week 8

ID	Title	Description
OG000	Pradaxa, 30 Minutes After a Meal (Randomized)	Randomized patients that develop gastrointestinal symptoms (GIS) were orally administered to Pradaxa (dabigatran etexilate) 150 mg or Pradaxa (dabigatran etexilate) 75 mg twice daily ( b.i.d.) taken with food (150 mg or 110 mg b.i.d. in Canada), within 30 minutes after a meal (4 weeks).
OG001	Pantoprazole 40 mg (Randomized)	Randomized patients that develop gastrointestinal symptoms (GIS) were orally administered to delayed release tablet pantoprazole 40 mg once daily in the Morning (q.a.m) (4 weeks).

Units	Counts
Participants

Secondary

Rate of Partial Effectiveness of Combined GIS Management Strategies

The percentage of patients experiencing partial relief of gastrointestinal symptoms (GIS) when taking pantoprazole 40 mg once daily in the morning (q.a.m.) vs. administration of Pradaxa ® (dabigatran etexilate) within 30 minutes after a meal at 4 weeks.

Partial effectiveness is defined as at the time of evaluation, either primary GIS is improved; or primary GIS is resolved, but there were still un-resolved secondary GIS.

Full Analysis Set (FAS)

Posted

Number

percentage of participants

Week 8

ID	Title	Description
OG000	Pradaxa, 30 Minutes After a Meal (Randomized)	Randomized patients that develop gastrointestinal symptoms (GIS) were orally administered to Pradaxa (dabigatran etexilate) 150 mg or Pradaxa (dabigatran etexilate) 75 mg twice daily ( b.i.d.) taken with food (150 mg or 110 mg b.i.d. in Canada), within 30 minutes after a meal (4 weeks).
OG001	Pantoprazole 40 mg (Randomized)	Randomized patients that develop gastrointestinal symptoms (GIS) were orally administered to delayed release tablet pantoprazole 40 mg once daily in the Morning (q.a.m) (4 weeks).

Units	Counts

Secondary

Combined Rate of Complete or Partial Effectiveness of Combined GIS Management Strategies

The percentage of patients experiencing combined of complete or partial relief of gastrointestinal symptoms (GIS) when taking pantoprazole 40 mg once daily in the morning (q.a.m.) vs. administration of Pradaxa ® (dabigatran etexilate) within 30 minutes after a meal.

Full Analysis Set (FAS)

Posted

Number

percentage of participants

Week 8

ID	Title	Description
OG000	Pradaxa, 30 Minutes After a Meal (Randomized)	Randomized patients that develop gastrointestinal symptoms (GIS) were orally administered to Pradaxa (dabigatran etexilate) 150 mg or Pradaxa (dabigatran etexilate) 75 mg twice daily ( b.i.d.) taken with food (150 mg or 110 mg b.i.d. in Canada), within 30 minutes after a meal (4 weeks).
OG001	Pantoprazole 40 mg (Randomized)	Randomized patients that develop gastrointestinal symptoms (GIS) were orally administered to delayed release tablet pantoprazole 40 mg once daily in the Morning (q.a.m) (4 weeks).

Secondary

Rates of Complete Effectiveness of GIS at Each Visit.

The percentage of patients experiencing complete effectiveness of gastrointestinal symptoms (GIS) at each visit by management strategy.

Evaluation of GIS was based on Last observation carried forward (LOCF) data up to the last observed time or up to adding the second management strategy.

Full analysis Set (FAS).

Posted

Number

percentage of participants

Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7 & Week 8

ID	Title	Description
OG000	Pradaxa, 30 Minutes After a Meal (Randomized)	Randomized patients that develop gastrointestinal symptoms (GIS) were orally administered to Pradaxa (dabigatran etexilate) 150 mg or Pradaxa (dabigatran etexilate) 75 mg twice daily ( b.i.d.) taken with food (150 mg or 110 mg b.i.d. in Canada), within 30 minutes after a meal (4 weeks).
OG001	Pantoprazole 40 mg (Randomized)	Randomized patients that develop gastrointestinal symptoms (GIS) were orally administered to delayed release tablet pantoprazole 40 mg once daily in the Morning (q.a.m) (4 weeks).

Units	Counts
Participants

Secondary

Rates of Partial Effectiveness of GIS at Each Visit.

The percentage of patients experiencing partial effectiveness of gastrointestinal symptoms (GIS) at each visit by management strategy.

Evaluation of GIS was based on Last observation carried forward (LOCF) data up to the last observed time or up to adding the second management strategy.

Full Analysis Set (FAS)

Posted

Number

percentage of participants

Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7 & Week 8

ID	Title	Description
OG000	Pradaxa, 30 Minutes After a Meal (Randomized)	Randomized patients that develop gastrointestinal symptoms (GIS) were orally administered to Pradaxa (dabigatran etexilate) 150 mg or Pradaxa (dabigatran etexilate) 75 mg twice daily ( b.i.d.) taken with food (150 mg or 110 mg b.i.d. in Canada), within 30 minutes after a meal (4 weeks).
OG001	Pantoprazole 40 mg (Randomized)	Randomized patients that develop gastrointestinal symptoms (GIS) were orally administered to delayed release tablet pantoprazole 40 mg once daily in the Morning (q.a.m) (4 weeks).

Units	Counts
Participants

Secondary

Rates of Complete or Partial Effectiveness of GIS at Each Visit.

The percentage of patients experiencing complete or partial effectiveness of gastrointestinal symptoms (GIS) at each visit by management strategy.

Evaluation of GIS was based on Last observation carried forward (LOCF) data up to the last observed time or up to adding the second management strategy.

Full Analysis Set (FAS).

Posted

Number

percentage of participants

Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7 & Week 8

ID	Title	Description
OG000	Pradaxa, 30 Minutes After a Meal (Randomized)	Randomized patients that develop gastrointestinal symptoms (GIS) were orally administered to Pradaxa (dabigatran etexilate) 150 mg or Pradaxa (dabigatran etexilate) 75 mg twice daily ( b.i.d.) taken with food (150 mg or 110 mg b.i.d. in Canada), within 30 minutes after a meal (4 weeks).
OG001	Pantoprazole 40 mg (Randomized)	Randomized patients that develop gastrointestinal symptoms (GIS) were orally administered to delayed release tablet pantoprazole 40 mg once daily in the Morning (q.a.m) (4 weeks).

Units	Counts
Participants

Secondary

Time Between Symptom Onset and First Observed Complete or Partial Effectiveness and Between Symptom Onset and Last Observed Symptom

Time between symptom onset and first observed complete or partial effectiveness and between symptom onset and last observed symptom by management strategy.

Full Analysis Set (FAS)

Posted

Mean

Standard Deviation

days

Week 8

ID	Title	Description
OG000	Pradaxa, 30 Minutes After a Meal (Randomized)	Randomized patients that develop gastrointestinal symptoms (GIS) were orally administered to Pradaxa (dabigatran etexilate) 150 mg or Pradaxa (dabigatran etexilate) 75 mg twice daily ( b.i.d.) taken with food (150 mg or 110 mg b.i.d. in Canada), within 30 minutes after a meal (4 weeks).
OG001	Pantoprazole 40 mg (Randomized)	Randomized patients that develop gastrointestinal symptoms (GIS) were orally administered to delayed release tablet pantoprazole 40 mg once daily in the Morning (q.a.m) (4 weeks).

Units	Counts
Participants

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Pradaxa, 30 Minutes After a Meal (Randomized)	Randomized patients that develop gastrointestinal symptoms (GIS) were orally administered to Pradaxa (dabigatran etexilate) 150 mg or Pradaxa (dabigatran etexilate) 75 mg twice daily ( b.i.d.) taken with food (150 mg or 110 mg b.i.d. in Canada), within 30 minutes after a meal (4 weeks).	2	59	37	59
EG001	Pantoprazole 40 mg (Randomized)	Randomized patients that develop gastrointestinal symptoms (GIS) were orally administered to delayed release tablet pantoprazole 40 mg once daily in the Morning (q.a.m) (4 weeks).	3	58	35	58
EG002	Pradaxa, Never Randomized	Patients who were treated for 3 months with Pradaxa ® and were never randomized to management strategies.	109	950	161	950

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0021 affected950 at risk
Haemorrhagic anaemia	Blood and lymphatic system disorders	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0021 affected950 at risk
Acute coronary syndrome	Cardiac disorders	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0021 affected950 at risk
Acute myocardial infarction	Cardiac disorders	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0021 affected950 at risk
Angina pectoris	Cardiac disorders	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0021 affected950 at risk
Atrial fibrillation	Cardiac disorders	17.0	Systematic Assessment	EG0001 affected59 at risk EG0012 affected58 at risk EG00222 affected950 at risk
Atrial flutter	Cardiac disorders	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0024 affected950 at risk
Atrial tachycardia	Cardiac disorders	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0021 affected950 at risk
Atrioventricular block complete	Cardiac disorders	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0022 affected950 at risk
Cardiac arrest	Cardiac disorders	17.0	Systematic Assessment	EG0001 affected59 at risk EG0010 affected58 at risk EG0022 affected950 at risk
Cardiac failure congestive	Cardiac disorders	17.0	Systematic Assessment	EG0000 affected59 at risk EG0011 affected58 at risk EG00221 affected950 at risk
Cardiac tamponade	Cardiac disorders	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0021 affected950 at risk
Coronary artery disease	Cardiac disorders	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0023 affected950 at risk
Mitral valve incompetence	Cardiac disorders	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0021 affected950 at risk
Mitral valve prolapse	Cardiac disorders	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0021 affected950 at risk
Myocardial ischaemia	Cardiac disorders	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0021 affected950 at risk
Palpitations	Cardiac disorders	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0021 affected950 at risk
Pericardial effusion	Cardiac disorders	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0021 affected950 at risk
Sick sinus syndrome	Cardiac disorders	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0024 affected950 at risk
Sinus bradycardia	Cardiac disorders	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0021 affected950 at risk
Ventricular tachycardia	Cardiac disorders	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0021 affected950 at risk
Congenital cyst	Congenital, familial and genetic disorders	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0021 affected950 at risk
Vertigo	Ear and labyrinth disorders	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0021 affected950 at risk
Diplopia	Eye disorders	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0021 affected950 at risk
Colon dysplasia	Gastrointestinal disorders	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0021 affected950 at risk
Dysphagia	Gastrointestinal disorders	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0021 affected950 at risk
Gastritis	Gastrointestinal disorders	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0021 affected950 at risk
Gastritis erosive	Gastrointestinal disorders	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0021 affected950 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0022 affected950 at risk
Large intestine polyp	Gastrointestinal disorders	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0021 affected950 at risk
Small intestinal obstruction	Gastrointestinal disorders	17.0	Systematic Assessment	EG0000 affected59 at risk EG0011 affected58 at risk EG0020 affected950 at risk
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0021 affected950 at risk
Chest pain	General disorders	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0025 affected950 at risk
Oedema peripheral	General disorders	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0021 affected950 at risk
Pain	General disorders	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0021 affected950 at risk
Pyrexia	General disorders	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0021 affected950 at risk
Systemic inflammatory response syndrome	General disorders	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0021 affected950 at risk
Cholelithiasis	Hepatobiliary disorders	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0021 affected950 at risk
Anaphylactic reaction	Immune system disorders	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0021 affected950 at risk
Bronchitis	Infections and infestations	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0021 affected950 at risk
Cellulitis	Infections and infestations	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0022 affected950 at risk
Gangrene	Infections and infestations	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0022 affected950 at risk
Gastroenteritis	Infections and infestations	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0021 affected950 at risk
Lobar pneumonia	Infections and infestations	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0021 affected950 at risk
Mastitis	Infections and infestations	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0021 affected950 at risk
Oesophageal candidiasis	Infections and infestations	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0021 affected950 at risk
Pneumonia	Infections and infestations	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0025 affected950 at risk
Staphylococcal sepsis	Infections and infestations	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0021 affected950 at risk
Urinary tract infection	Infections and infestations	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0021 affected950 at risk
Fall	Injury, poisoning and procedural complications	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0021 affected950 at risk
Femur fracture	Injury, poisoning and procedural complications	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0021 affected950 at risk
Humerus fracture	Injury, poisoning and procedural complications	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0021 affected950 at risk
Post procedural haemorrhage	Injury, poisoning and procedural complications	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0021 affected950 at risk
Procedural nausea	Injury, poisoning and procedural complications	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0021 affected950 at risk
Skull fractured base	Injury, poisoning and procedural complications	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0021 affected950 at risk
Toxicity to various agents	Injury, poisoning and procedural complications	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0022 affected950 at risk
Wound secretion	Injury, poisoning and procedural complications	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0021 affected950 at risk
Blood iron decreased	Investigations	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0021 affected950 at risk
Blood magnesium decreased	Investigations	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0021 affected950 at risk
Electrocardiogram ST segment depression	Investigations	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0021 affected950 at risk
Heart rate decreased	Investigations	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0021 affected950 at risk
Hepatic enzyme increased	Investigations	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0021 affected950 at risk
Troponin increased	Investigations	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0021 affected950 at risk
Dehydration	Metabolism and nutrition disorders	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0021 affected950 at risk
Diabetes mellitus inadequate control	Metabolism and nutrition disorders	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0022 affected950 at risk
Hypokalaemia	Metabolism and nutrition disorders	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0021 affected950 at risk
Hyponatraemia	Metabolism and nutrition disorders	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0021 affected950 at risk
Bursitis	Musculoskeletal and connective tissue disorders	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0022 affected950 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0021 affected950 at risk
Anal cancer stage 0	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0021 affected950 at risk
Bladder cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0021 affected950 at risk
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0021 affected950 at risk
Squamous cell carcinoma of the tongue	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0021 affected950 at risk
Cerebral thrombosis	Nervous system disorders	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0021 affected950 at risk
Cerebrovascular accident	Nervous system disorders	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0021 affected950 at risk
Embolic stroke	Nervous system disorders	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0023 affected950 at risk
Haemorrhage intracranial	Nervous system disorders	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0021 affected950 at risk
Haemorrhagic stroke	Nervous system disorders	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0021 affected950 at risk
Ischaemic stroke	Nervous system disorders	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0021 affected950 at risk
Syncope	Nervous system disorders	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0023 affected950 at risk
Transient ischaemic attack	Nervous system disorders	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0022 affected950 at risk
Acute prerenal failure	Renal and urinary disorders	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0021 affected950 at risk
Renal failure acute	Renal and urinary disorders	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0025 affected950 at risk
Renal failure chronic	Renal and urinary disorders	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0021 affected950 at risk
Urinary retention	Renal and urinary disorders	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0021 affected950 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0023 affected950 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0022 affected950 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0022 affected950 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0023 affected950 at risk
Pulmonary hypertension	Respiratory, thoracic and mediastinal disorders	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0023 affected950 at risk
Respiratory arrest	Respiratory, thoracic and mediastinal disorders	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0021 affected950 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0021 affected950 at risk
Cardiac pacemaker insertion	Surgical and medical procedures	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0021 affected950 at risk
Hypertensive crisis	Vascular disorders	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0021 affected950 at risk
Hypotension	Vascular disorders	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0021 affected950 at risk
Peripheral arterial occlusive disease	Vascular disorders	17.0	Systematic Assessment	EG0000 affected59 at risk EG0010 affected58 at risk EG0021 affected950 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal discomfort	Gastrointestinal disorders	17.0	Systematic Assessment	EG0007 affected59 at risk EG00113 affected58 at risk EG00225 affected950 at risk
Abdominal distension	Gastrointestinal disorders	17.0	Systematic Assessment	EG0008 affected59 at risk EG00112 affected58 at risk EG00223 affected950 at risk
Abdominal pain upper	Gastrointestinal disorders	17.0	Systematic Assessment	EG0008 affected59 at risk EG00110 affected58 at risk EG00226 affected950 at risk
Constipation	Gastrointestinal disorders	17.0	Systematic Assessment	EG0003 affected59 at risk EG0014 affected58 at risk EG00212 affected950 at risk
Defaecation urgency	Gastrointestinal disorders	17.0	Systematic Assessment	EG0004 affected59 at risk EG0012 affected58 at risk EG0020 affected950 at risk
Diarrhoea	Gastrointestinal disorders	17.0	Systematic Assessment	EG0007 affected59 at risk EG0017 affected58 at risk EG00230 affected950 at risk
Dyspepsia	Gastrointestinal disorders	17.0	Systematic Assessment	EG00017 affected59 at risk EG00115 affected58 at risk EG00273 affected950 at risk
Epigastric discomfort	Gastrointestinal disorders	17.0	Systematic Assessment	EG0009 affected59 at risk EG00110 affected58 at risk EG00218 affected950 at risk
Eructation	Gastrointestinal disorders	17.0	Systematic Assessment	EG00013 affected59 at risk EG00110 affected58 at risk EG00225 affected950 at risk
Faeces hard	Gastrointestinal disorders	17.0	Systematic Assessment	EG0001 affected59 at risk EG0013 affected58 at risk EG0021 affected950 at risk
Flatulence	Gastrointestinal disorders	17.0	Systematic Assessment	EG0005 affected59 at risk EG0015 affected58 at risk EG00214 affected950 at risk
Gastrointestinal sounds abnormal	Gastrointestinal disorders	17.0	Systematic Assessment	EG0004 affected59 at risk EG0012 affected58 at risk EG0020 affected950 at risk
Nausea	Gastrointestinal disorders	17.0	Systematic Assessment	EG0005 affected59 at risk EG00110 affected58 at risk EG00231 affected950 at risk
Regurgitation	Gastrointestinal disorders	17.0	Systematic Assessment	EG0009 affected59 at risk EG0014 affected58 at risk EG00215 affected950 at risk
Dizziness	Nervous system disorders	17.0	Systematic Assessment	EG0003 affected59 at risk EG0012 affected58 at risk EG00220 affected950 at risk
Bronchitis	Infections and infestations	17.0	Systematic Assessment	EG0003 affected59 at risk EG0011 affected58 at risk EG00218 affected950 at risk
Headache	Nervous system disorders	17.0	Systematic Assessment	EG0001 affected59 at risk EG0013 affected58 at risk EG00211 affected950 at risk

ID	Term
D001145	Arrhythmias, Cardiac
D006331	Heart Diseases
D002318	Cardiovascular Diseases
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms

ID	Term
D053799	2-Pyridinylmethylsulfinylbenzimidazoles
D013454	Sulfoxides
D013457	Sulfur Compounds
D009930	Organic Chemicals
D011725	Pyridines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D001562	Benzimidazoles
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D004068	Digestive System Physiological Phenomena
D055688	Digestive System and Oral Physiological Phenomena

ID	Term
D000077402	Pantoprazole
D000069604	Dabigatran
D019518	Postprandial Period