Trial Outcomes & Findings for A Prospective, Open Label Study Evaluating Two Management Strategies on Gastrointestinal Symptoms in Patients Newly on Treatment With Pradaxa for the Prevention of Stroke and Systemic Embolism With Non-valvular Atrial Fibrillation (NCT NCT01493557)

Last Updated: 2015-10-05

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

1067 participants

Primary outcome timeframe

Week 4

Results posted on

2015-10-05

Participant Flow

This is a Prospective, randomized, open label trial. 1067 patients treated with Pradaxa and 117 patients were randomized to a management strategy. NVAF= non-valvular atrial fibrillation and GIS = gastrointestinal symptoms.

Participant milestones

Participant milestones
Measure	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).	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).	Pradaxa, Never Randomized Patients who were treated for 3 months with Pradaxa ® and were never randomized to management strategies.
Not Randomized to Management Strategies STARTED	0	0	950
Not Randomized to Management Strategies Without Experiencing GIS	0	0	854
Not Randomized to Management Strategies Reported GIS Prior to EOT Visit	0	0	48
Not Randomized to Management Strategies Reported GIS Only at EOT Visit	0	0	48
Not Randomized to Management Strategies COMPLETED	0	0	816
Not Randomized to Management Strategies NOT COMPLETED	0	0	134
Randomized to Management Strategies STARTED	59	58	0
Randomized to Management Strategies COMPLETED	44	47	0
Randomized to Management Strategies NOT COMPLETED	15	11	0
Adding the Second Strategy STARTED	14	15	0
Adding the Second Strategy COMPLETED	12	11	0
Adding the Second Strategy NOT COMPLETED	2	4	0

Reasons for withdrawal

Reasons for withdrawal
Measure	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).	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).	Pradaxa, Never Randomized Patients who were treated for 3 months with Pradaxa ® and were never randomized to management strategies.
Not Randomized to Management Strategies Worsening of events associate with NVAF.	0	0	1
Not Randomized to Management Strategies Worsening of other pre-existing disease	0	0	9
Not Randomized to Management Strategies Other adverse event	0	0	54
Not Randomized to Management Strategies Protocol Violation	0	0	1
Not Randomized to Management Strategies Lost to Follow-up	0	0	4
Not Randomized to Management Strategies Withdrawal by Subject	0	0	10
Not Randomized to Management Strategies Early termination	0	0	34
Not Randomized to Management Strategies Other than stated above	0	0	21
Randomized to Management Strategies Worsening of events associate with GIS	3	2	0
Randomized to Management Strategies Other adverse event	8	5	0
Randomized to Management Strategies Protocol Violation	3	0	0
Randomized to Management Strategies Withdrawal by Subject	0	1	0
Randomized to Management Strategies Other than stated above	1	3	0
Adding the Second Strategy Worsening of events associate with GIS	1	1	0
Adding the Second Strategy Other adverse event	1	2	0
Adding the Second Strategy Withdrawal by Subject	0	1	0

Baseline Characteristics

A Prospective, Open Label Study Evaluating Two Management Strategies on Gastrointestinal Symptoms in Patients Newly on Treatment With Pradaxa for the Prevention of Stroke and Systemic Embolism With Non-valvular Atrial Fibrillation

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pradaxa, 30 Minutes After a Meal (Randomized) n=59 Participants 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).	Pantoprazole 40 mg (Randomized) n=58 Participants 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).	Pradaxa, Never Randomized n=950 Participants Patients who were treated for 3 months with Pradaxa ® and were never randomized to management strategies.	Total n=1067 Participants Total of all reporting groups
Age, Continuous	69.1 Years STANDARD_DEVIATION 11.1 • n=93 Participants	69.6 Years STANDARD_DEVIATION 10.8 • n=4 Participants	69.7 Years STANDARD_DEVIATION 10.7 • n=27 Participants	69.7 Years STANDARD_DEVIATION 10.7 • n=483 Participants
Sex: Female, Male Female	22 Participants n=93 Participants	20 Participants n=4 Participants	304 Participants n=27 Participants	346 Participants n=483 Participants
Sex: Female, Male Male	37 Participants n=93 Participants	38 Participants n=4 Participants	646 Participants n=27 Participants	721 Participants n=483 Participants

PRIMARY outcome

Timeframe: Week 4

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

Outcome measures

Outcome measures
Measure	Pradaxa, 30 Minutes After a Meal (Randomized) n=59 Participants 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).	Pantoprazole 40 mg (Randomized) n=58 Participants 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).
The Rate of Complete Effectiveness of Initial GIS Management Strategy	55.9 percentage of participants	67.2 percentage of participants

SECONDARY outcome

Timeframe: Week 4

Population: Full Analysis Set (FAS)

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.

Outcome measures

Outcome measures
Measure	Pradaxa, 30 Minutes After a Meal (Randomized) n=59 Participants 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).	Pantoprazole 40 mg (Randomized) n=58 Participants 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).
Rate of Partial Effectiveness of Initial GIS Management Strategies	11.9 percentage of participants	19.0 percentage of participants

SECONDARY outcome

Timeframe: Week 4

Population: Full Analysis Set (FAS)

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.

Outcome measures

Outcome measures
Measure	Pradaxa, 30 Minutes After a Meal (Randomized) n=59 Participants 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).	Pantoprazole 40 mg (Randomized) n=58 Participants 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).
Combined Rate of Complete or Partial Effectiveness of Initial GIS Management Strategies	67.8 percentage of participants	86.2 percentage of participants

SECONDARY outcome

Timeframe: Week 8

Population: Full Analysis Set (FAS)

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.

Outcome measures

Outcome measures
Measure	Pradaxa, 30 Minutes After a Meal (Randomized) n=14 Participants 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).	Pantoprazole 40 mg (Randomized) n=15 Participants 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).
Rate of Complete Effectiveness of Combined GIS Management Strategies	42.9 percentage of participants	33.3 percentage of participants

SECONDARY outcome

Timeframe: Week 8

Population: Full Analysis Set (FAS)

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.

Outcome measures

Outcome measures
Measure	Pradaxa, 30 Minutes After a Meal (Randomized) n=14 Participants 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).	Pantoprazole 40 mg (Randomized) n=15 Participants 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).
Rate of Partial Effectiveness of Combined GIS Management Strategies	42.9 percentage of participants	46.7 percentage of participants

SECONDARY outcome

Timeframe: Week 8

Population: Full Analysis Set (FAS)

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. 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.

Outcome measures

Outcome measures
Measure	Pradaxa, 30 Minutes After a Meal (Randomized) n=14 Participants 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).	Pantoprazole 40 mg (Randomized) n=15 Participants 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).
Combined Rate of Complete or Partial Effectiveness of Combined GIS Management Strategies	85.7 percentage of participants	80.0 percentage of participants

SECONDARY outcome

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

Population: Full analysis Set (FAS).

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.

Outcome measures

Outcome measures
Measure	Pradaxa, 30 Minutes After a Meal (Randomized) n=59 Participants 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).	Pantoprazole 40 mg (Randomized) n=58 Participants 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).
Rates of Complete Effectiveness of GIS at Each Visit. Baseline (n= 59 , 58)	0.0 percentage of participants	0.0 percentage of participants
Rates of Complete Effectiveness of GIS at Each Visit. GIS 3 (Week 1, n= 59 , 58)	39.0 percentage of participants	51.7 percentage of participants
Rates of Complete Effectiveness of GIS at Each Visit. GIS 4 (Week 2, n= 59 , 58)	45.8 percentage of participants	55.2 percentage of participants
Rates of Complete Effectiveness of GIS at Each Visit. GIS 5 (Week 3, n= 59 , 58)	55.9 percentage of participants	60.3 percentage of participants
Rates of Complete Effectiveness of GIS at Each Visit. GIS 6 (Week 4, n= 59 , 58)	55.9 percentage of participants	67.2 percentage of participants
Rates of Complete Effectiveness of GIS at Each Visit. GIS 7 (Week 5, n= 14 , 15)	28.6 percentage of participants	40.0 percentage of participants
Rates of Complete Effectiveness of GIS at Each Visit. GIS 8 (Week 6, n= 14 , 15)	42.9 percentage of participants	40.0 percentage of participants
Rates of Complete Effectiveness of GIS at Each Visit. GIS 9 (Week 7, n= 14 , 15)	42.9 percentage of participants	33.3 percentage of participants
Rates of Complete Effectiveness of GIS at Each Visit. GIS 10 (Week 8, n= 14 , 15)	42.9 percentage of participants	33.3 percentage of participants

SECONDARY outcome

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

Population: Full Analysis Set (FAS)

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.

Outcome measures

Outcome measures
Measure	Pradaxa, 30 Minutes After a Meal (Randomized) n=59 Participants 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).	Pantoprazole 40 mg (Randomized) n=58 Participants 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).
Rates of Partial Effectiveness of GIS at Each Visit. Baseline (n= 59 , 58)	0.0 percentage of participants	0.0 percentage of participants
Rates of Partial Effectiveness of GIS at Each Visit. GIS 3 (Week 1, n= 59 , 58)	16.9 percentage of participants	13.8 percentage of participants
Rates of Partial Effectiveness of GIS at Each Visit. GIS 4 (Week 2, n= 59 , 58)	13.6 percentage of participants	24.1 percentage of participants
Rates of Partial Effectiveness of GIS at Each Visit. GIS 5 (Week 3, n= 59 , 58)	8.5 percentage of participants	22.4 percentage of participants
Rates of Partial Effectiveness of GIS at Each Visit. GIS 6 (Week 4, n= 59 , 58)	11.9 percentage of participants	19.0 percentage of participants
Rates of Partial Effectiveness of GIS at Each Visit. GIS 7 (Week 5, n= 14 , 15)	21.4 percentage of participants	40.0 percentage of participants
Rates of Partial Effectiveness of GIS at Each Visit. GIS 8 (Week 6, n= 14 , 15)	42.9 percentage of participants	40.0 percentage of participants
Rates of Partial Effectiveness of GIS at Each Visit. GIS 9 (Week 7, n= 14 , 15)	42.9 percentage of participants	46.7 percentage of participants
Rates of Partial Effectiveness of GIS at Each Visit. GIS 10 (Week 8, n= 14 , 15)	42.9 percentage of participants	46.7 percentage of participants

SECONDARY outcome

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

Population: Full Analysis Set (FAS).

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.

Outcome measures

Outcome measures
Measure	Pradaxa, 30 Minutes After a Meal (Randomized) n=59 Participants 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).	Pantoprazole 40 mg (Randomized) n=58 Participants 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).
Rates of Complete or Partial Effectiveness of GIS at Each Visit. Baseline (n= 59 , 58)	0.0 percentage of participants	0.0 percentage of participants
Rates of Complete or Partial Effectiveness of GIS at Each Visit. GIS 3 (Week 1, n= 59 , 58)	55.9 percentage of participants	65.5 percentage of participants
Rates of Complete or Partial Effectiveness of GIS at Each Visit. GIS 4 (Week 2, n= 59 , 58)	59.3 percentage of participants	79.3 percentage of participants
Rates of Complete or Partial Effectiveness of GIS at Each Visit. GIS 5 (Week 3, n= 59 , 58)	64.4 percentage of participants	82.8 percentage of participants
Rates of Complete or Partial Effectiveness of GIS at Each Visit. GIS 6 (Week 4, n= 59 , 58)	67.8 percentage of participants	86.2 percentage of participants
Rates of Complete or Partial Effectiveness of GIS at Each Visit. GIS 7 (Week 5, n= 14 , 15)	50.0 percentage of participants	80.0 percentage of participants
Rates of Complete or Partial Effectiveness of GIS at Each Visit. GIS 8 (Week 6, n= 14 , 15)	85.7 percentage of participants	80.0 percentage of participants
Rates of Complete or Partial Effectiveness of GIS at Each Visit. GIS 9 (Week 7, n= 14 , 15)	85.7 percentage of participants	80.0 percentage of participants
Rates of Complete or Partial Effectiveness of GIS at Each Visit. GIS 10 (Week 8, n= 14 , 15)	85.7 percentage of participants	80.0 percentage of participants

SECONDARY outcome

Timeframe: Week 8

Population: Full Analysis Set (FAS)

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

Outcome measures

Outcome measures
Measure	Pradaxa, 30 Minutes After a Meal (Randomized) n=59 Participants 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).	Pantoprazole 40 mg (Randomized) n=58 Participants 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).
Time Between Symptom Onset and First Observed Complete or Partial Effectiveness and Between Symptom Onset and Last Observed Symptom Duration of GIS (N= 58; 58)	23.5 days Standard Deviation 25.67	23.9 days Standard Deviation 25.35
Time Between Symptom Onset and First Observed Complete or Partial Effectiveness and Between Symptom Onset and Last Observed Symptom Time to first complete effectiveness (N= 43; 50)	12.1 days Standard Deviation 13.45	10.7 days Standard Deviation 10.23
Time Between Symptom Onset and First Observed Complete or Partial Effectiveness and Between Symptom Onset and Last Observed Symptom Time to first partial effectiveness(N= 6; 2)	23.7 days Standard Deviation 15.50	3.5 days Standard Deviation 2.12

Adverse Events

Pradaxa, 30 Minutes After a Meal (Randomized)

Serious events: 2 serious events

Other events: 37 other events

Deaths: 0 deaths

Pantoprazole 40 mg (Randomized)

Serious events: 3 serious events

Other events: 35 other events

Deaths: 0 deaths

Pradaxa, Never Randomized

Serious events: 109 serious events

Other events: 161 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Boehringer Ingelheim Call Center

Boehringer Ingelheim Pharmaceuticals

Phone: 1-800-243-0127

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER

Measure	Pradaxa, 30 Minutes After a Meal (Randomized) n=59 participants at risk 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).	Pantoprazole 40 mg (Randomized) n=58 participants at risk 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).	Pradaxa, Never Randomized n=950 participants at risk Patients who were treated for 3 months with Pradaxa ® and were never randomized to management strategies.
Gastrointestinal disorders Abdominal discomfort	11.9% 7/59 • From first drug administration until 6 days after end of trial, up to 158 days.	22.4% 13/58 • From first drug administration until 6 days after end of trial, up to 158 days.	2.6% 25/950 • From first drug administration until 6 days after end of trial, up to 158 days.
Gastrointestinal disorders Abdominal distension	13.6% 8/59 • From first drug administration until 6 days after end of trial, up to 158 days.	20.7% 12/58 • From first drug administration until 6 days after end of trial, up to 158 days.	2.4% 23/950 • From first drug administration until 6 days after end of trial, up to 158 days.
Gastrointestinal disorders Abdominal pain upper	13.6% 8/59 • From first drug administration until 6 days after end of trial, up to 158 days.	17.2% 10/58 • From first drug administration until 6 days after end of trial, up to 158 days.	2.7% 26/950 • From first drug administration until 6 days after end of trial, up to 158 days.
Gastrointestinal disorders Constipation	5.1% 3/59 • From first drug administration until 6 days after end of trial, up to 158 days.	6.9% 4/58 • From first drug administration until 6 days after end of trial, up to 158 days.	1.3% 12/950 • From first drug administration until 6 days after end of trial, up to 158 days.
Gastrointestinal disorders Defaecation urgency	6.8% 4/59 • From first drug administration until 6 days after end of trial, up to 158 days.	3.4% 2/58 • From first drug administration until 6 days after end of trial, up to 158 days.	0.00% 0/950 • From first drug administration until 6 days after end of trial, up to 158 days.
Gastrointestinal disorders Diarrhoea	11.9% 7/59 • From first drug administration until 6 days after end of trial, up to 158 days.	12.1% 7/58 • From first drug administration until 6 days after end of trial, up to 158 days.	3.2% 30/950 • From first drug administration until 6 days after end of trial, up to 158 days.
Gastrointestinal disorders Dyspepsia	28.8% 17/59 • From first drug administration until 6 days after end of trial, up to 158 days.	25.9% 15/58 • From first drug administration until 6 days after end of trial, up to 158 days.	7.7% 73/950 • From first drug administration until 6 days after end of trial, up to 158 days.
Gastrointestinal disorders Epigastric discomfort	15.3% 9/59 • From first drug administration until 6 days after end of trial, up to 158 days.	17.2% 10/58 • From first drug administration until 6 days after end of trial, up to 158 days.	1.9% 18/950 • From first drug administration until 6 days after end of trial, up to 158 days.
Gastrointestinal disorders Eructation	22.0% 13/59 • From first drug administration until 6 days after end of trial, up to 158 days.	17.2% 10/58 • From first drug administration until 6 days after end of trial, up to 158 days.	2.6% 25/950 • From first drug administration until 6 days after end of trial, up to 158 days.
Gastrointestinal disorders Faeces hard	1.7% 1/59 • From first drug administration until 6 days after end of trial, up to 158 days.	5.2% 3/58 • From first drug administration until 6 days after end of trial, up to 158 days.	0.11% 1/950 • From first drug administration until 6 days after end of trial, up to 158 days.
Gastrointestinal disorders Flatulence	8.5% 5/59 • From first drug administration until 6 days after end of trial, up to 158 days.	8.6% 5/58 • From first drug administration until 6 days after end of trial, up to 158 days.	1.5% 14/950 • From first drug administration until 6 days after end of trial, up to 158 days.
Gastrointestinal disorders Gastrointestinal sounds abnormal	6.8% 4/59 • From first drug administration until 6 days after end of trial, up to 158 days.	3.4% 2/58 • From first drug administration until 6 days after end of trial, up to 158 days.	0.00% 0/950 • From first drug administration until 6 days after end of trial, up to 158 days.
Gastrointestinal disorders Nausea	8.5% 5/59 • From first drug administration until 6 days after end of trial, up to 158 days.	17.2% 10/58 • From first drug administration until 6 days after end of trial, up to 158 days.	3.3% 31/950 • From first drug administration until 6 days after end of trial, up to 158 days.
Gastrointestinal disorders Regurgitation	15.3% 9/59 • From first drug administration until 6 days after end of trial, up to 158 days.	6.9% 4/58 • From first drug administration until 6 days after end of trial, up to 158 days.	1.6% 15/950 • From first drug administration until 6 days after end of trial, up to 158 days.
Nervous system disorders Dizziness	5.1% 3/59 • From first drug administration until 6 days after end of trial, up to 158 days.	3.4% 2/58 • From first drug administration until 6 days after end of trial, up to 158 days.	2.1% 20/950 • From first drug administration until 6 days after end of trial, up to 158 days.
Infections and infestations Bronchitis	5.1% 3/59 • From first drug administration until 6 days after end of trial, up to 158 days.	1.7% 1/58 • From first drug administration until 6 days after end of trial, up to 158 days.	1.9% 18/950 • From first drug administration until 6 days after end of trial, up to 158 days.
Nervous system disorders Headache	1.7% 1/59 • From first drug administration until 6 days after end of trial, up to 158 days.	5.2% 3/58 • From first drug administration until 6 days after end of trial, up to 158 days.	1.2% 11/950 • From first drug administration until 6 days after end of trial, up to 158 days.