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

Atrial Fibrillation Clinical Trial

Official title:

A Prospective, Open Label Study Evaluating the Efficacy of Two Management Strategies (Pantoprazole 40 mg q.a.m. and Taking Pradaxa® With Food (Within 30 Minutes After a Meal) on Gastrointestinal Symptoms (GIS) in Patients Newly on Treatment With Pradaxa® 150 mg b.i.d., 110 mg b.i.d. or 75 mg b.i.d. for the Prevention of Stroke and Systemic Embolism in Patients With Non-valvular Atrial Fibrillation (NVAF)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01493557
• Other study ID #: 1160.128
• Status: Completed
• Phase: Phase 4
• First received: December 12, 2011
• Last updated: September 2, 2015
• Start date: December 2011
• Est. completion date: July 2014

Study information

• Verified date: September 2015
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health CanadaUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

This is a prospective and open label study that aims to enroll approximately 1200 patients with non-valvular atrial fibrillation (NVAF) not previously treated with Pradaxa® and free of gastrointestinal symptoms (GIS) for at least 2 weeks prior to enrolment. Approximately 125 sites in North America will be recruited. Patients who report GIS during the 3 month treatment period will be randomized to one of two management strategies, and data documenting the intensity and duration of the GIS will be collected.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1067
• Est. completion date: July 2014
• Est. primary completion date: July 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion criteria:

1. 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

2. Male and female patients, age greater than or equal to 18 years at entry

3. Written, informed consent

Exclusion criteria:

1. 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.)

2. 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.)

3. Contraindication to pantoprazole or other proton pump inhibitors, e.g. omeprazole, lansoprazole, rabeprazole, atnoprazole, esomeprazole

4. Contraindication to Pradaxa® (dabigatran etexilate) or known hypersensitivity to Pradaxa® (dabigatran etexilate) or its excipients

5. Hemorrhagic disorder, bleeding diathesis or active pathological bleeding

6. Need for anticoagulant treatment for disorders other than atrial fibrillation

7. Current treatment with rifampin

8. Creatinine clearance <15ml/min (in Canada, <30ml/min), or patients on renal replacement therapy (dialysis)

9. 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.

10. Patients who have received an investigational drug in the past 30 days or are participating in another drug study

11. Patients considered unreliable by the investigator concerning the requirements for follow-up during the study

12. Any condition the investigator believes would not allow safe participation in the study

13. 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.

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Atrial Fibrillation

Intervention

Drug:
• pantoprazole
40 mg q.a.m, p.o.
• Pradaxa (dabigatran etexilate)
150 mg or 75 mg b.i.d. (150 mg or 110 mg b.i.d. in Canada)
• Pradaxa, within 30 minutes after a meal
Patients randomized to this intervention would be instructed to take their dabigatran 30 minutes after a meal
• Pradaxa (dabigatran etexilate)
150 mg or 75 mg b.i.d. (150 mg or 110 mg b.i.d. in Canada)

Locations

Country	Name	City	State
Canada	1160.128.1166 Boehringer Ingelheim Investigational Site	Bay Roberts	Newfoundland and Labrador
Canada	1160.128.1151 Boehringer Ingelheim Investigational Site	Brampton	Ontario
Canada	1160.128.1160 Boehringer Ingelheim Investigational Site	Calgary	Alberta
Canada	1160.128.1168 Boehringer Ingelheim Investigational Site	Cambridge	Ontario
Canada	1160.128.1164 Boehringer Ingelheim Investigational Site	Collingwood	Ontario
Canada	1160.128.1167 Boehringer Ingelheim Investigational Site	Coquitlam	British Columbia
Canada	1160.128.1173 Boehringer Ingelheim Investigational Site	Corunna	Ontario
Canada	1160.128.1159 Boehringer Ingelheim Investigational Site	Edmonton	Alberta
Canada	1160.128.1156 Boehringer Ingelheim Investigational Site	Hamilton	Ontario
Canada	1160.128.1157 Boehringer Ingelheim Investigational Site	Kitchener	Ontario
Canada	1160.128.1155 Boehringer Ingelheim Investigational Site	London	Ontario
Canada	1160.128.1170 Boehringer Ingelheim Investigational Site	Peterborough	Ontario
Canada	1160.128.1152 Boehringer Ingelheim Investigational Site	Red Deer	Alberta
Canada	1160.128.1154 Boehringer Ingelheim Investigational Site	Saint John	New Brunswick
Canada	1160.128.1165 Boehringer Ingelheim Investigational Site	Sarnia	Ontario
Canada	1160.128.1169 Boehringer Ingelheim Investigational Site	Sarnia	Ontario
Canada	1160.128.1172 Boehringer Ingelheim Investigational Site	Saskatoon	Saskatchewan
Canada	1160.128.1153 Boehringer Ingelheim Investigational Site	Spruce Grove	Alberta
Canada	1160.128.1161 Boehringer Ingelheim Investigational Site	Stayner	Ontario
Canada	1160.128.1171 Boehringer Ingelheim Investigational Site	Sudbury	Ontario
Canada	1160.128.1162 Boehringer Ingelheim Investigational Site	Toronto	Ontario
Canada	1160.128.1158 Boehringer Ingelheim Investigational Site	Victoria	British Columbia
United States	1160.128.1036 Boehringer Ingelheim Investigational Site	Albuquerque	New Mexico
United States	1160.128.1037 Boehringer Ingelheim Investigational Site	Altoona	Pennsylvania
United States	1160.128.1022 Boehringer Ingelheim Investigational Site	Asheville	North Carolina
United States	1160.128.1111 Boehringer Ingelheim Investigational Site	Atlantis	Florida
United States	1160.128.1025 Boehringer Ingelheim Investigational Site	Auburn	Maine
United States	1160.128.1006 Boehringer Ingelheim Investigational Site	Austin	Texas
United States	1160.128.1008 Boehringer Ingelheim Investigational Site	Baton Rouge	Louisiana
United States	1160.128.1053 Boehringer Ingelheim Investigational Site	Bend	Oregon
United States	1160.128.1100 Boehringer Ingelheim Investigational Site	Biddeford	Maine
United States	1160.128.1046 Boehringer Ingelheim Investigational Site	Birmingham	Alabama
United States	1160.128.1032 Boehringer Ingelheim Investigational Site	Brandon	Florida
United States	1160.128.1016 Boehringer Ingelheim Investigational Site	Bridgeport	Connecticut
United States	1160.128.1066 Boehringer Ingelheim Investigational Site	Bridgeport	Connecticut
United States	1160.128.1034 Boehringer Ingelheim Investigational Site	Camp Hill	Pennsylvania
United States	1160.128.1093 Boehringer Ingelheim Investigational Site	Chandler	Arizona
United States	1160.128.1043 Boehringer Ingelheim Investigational Site	Charleston	South Carolina
United States	1160.128.1076 Boehringer Ingelheim Investigational Site	Coeur d' Alene	Idaho
United States	1160.128.1005 Boehringer Ingelheim Investigational Site	Colorado Spring	Colorado
United States	1160.128.1014 Boehringer Ingelheim Investigational Site	Columbia	Missouri
United States	1160.128.1041 Boehringer Ingelheim Investigational Site	Columbia	Maryland
United States	1160.128.1096 Boehringer Ingelheim Investigational Site	Columbus	Georgia
United States	1160.128.1021 Boehringer Ingelheim Investigational Site	Coral Springs	Florida
United States	1160.128.1077 Boehringer Ingelheim Investigational Site	Danville	Virginia
United States	1160.128.1027 Boehringer Ingelheim Investigational Site	Daytona Beach	Florida
United States	1160.128.1023 Boehringer Ingelheim Investigational Site	Denver	Colorado
United States	1160.128.1039 Boehringer Ingelheim Investigational Site	Elmer	New Jersey
United States	1160.128.1064 Boehringer Ingelheim Investigational Site	Falls Church	Virginia
United States	1160.128.1035 Boehringer Ingelheim Investigational Site	Flemington	New Jersey
United States	1160.128.1091 Boehringer Ingelheim Investigational Site	Gallipolis	Ohio
United States	1160.128.1052 Boehringer Ingelheim Investigational Site	Gastonia	North Carolina
United States	1160.128.1069 Boehringer Ingelheim Investigational Site	Great Falls	Montana
United States	1160.128.1018 Boehringer Ingelheim Investigational Site	Guilford	Connecticut
United States	1160.128.1105 Boehringer Ingelheim Investigational Site	Hammond	Indiana
United States	1160.128.1063 Boehringer Ingelheim Investigational Site	Hawthorne	New York
United States	1160.128.1033 Boehringer Ingelheim Investigational Site	Hillsboro	Oregon
United States	1160.128.1067 Boehringer Ingelheim Investigational Site	Hot Springs	Arkansas
United States	1160.128.1104 Boehringer Ingelheim Investigational Site	Houston	Texas
United States	1160.128.1045 Boehringer Ingelheim Investigational Site	Huntsville	Alabama
United States	1160.128.1029 Boehringer Ingelheim Investigational Site	Indianapolis	Indiana
United States	1160.128.1019 Boehringer Ingelheim Investigational Site	Jacksonville	Florida
United States	1160.128.1062 Boehringer Ingelheim Investigational Site	Jacksonville	Florida
United States	1160.128.1011 Boehringer Ingelheim Investigational Site	Kalispell	Montana
United States	1160.128.1047 Boehringer Ingelheim Investigational Site	Kansas City	Missouri
United States	1160.128.1010 Boehringer Ingelheim Investigational Site	Langhorne	Pennsylvania
United States	1160.128.1054 Boehringer Ingelheim Investigational Site	Largo	Florida
United States	1160.128.1102 Boehringer Ingelheim Investigational Site	Layton	Utah
United States	1160.128.1092 Boehringer Ingelheim Investigational Site	Lincoln	Nebraska
United States	1160.128.1110 Boehringer Ingelheim Investigational Site	Manassas	Virginia
United States	1160.128.1061 Boehringer Ingelheim Investigational Site	McKinney	Texas
United States	1160.128.1073 Boehringer Ingelheim Investigational Site	Melrose Park	Illinois
United States	1160.128.1103 Boehringer Ingelheim Investigational Site	Mesa	California
United States	1160.128.1097 Boehringer Ingelheim Investigational Site	Miami	Florida
United States	1160.128.1109 Boehringer Ingelheim Investigational Site	Miami	Florida
United States	1160.128.1078 Boehringer Ingelheim Investigational Site	Mineola	New York
United States	1160.128.1003 Boehringer Ingelheim Investigational Site	Mobile	Alabama
United States	1160.128.1090 Boehringer Ingelheim Investigational Site	New Braunfels	Texas
United States	1160.128.1094 Boehringer Ingelheim Investigational Site	Newport Beach	California
United States	1160.128.1099 Boehringer Ingelheim Investigational Site	Norfolk	Virginia
United States	1160.128.1050 Boehringer Ingelheim Investigational Site	Norwalk	Connecticut
United States	1160.128.1107 Boehringer Ingelheim Investigational Site	Oklahoma City	Oklahoma
United States	1160.128.1059 Boehringer Ingelheim Investigational Site	Omaha	Nebraska
United States	1160.128.1087 Boehringer Ingelheim Investigational Site	Orlando	Florida
United States	1160.128.1079 Boehringer Ingelheim Investigational Site	Overland Park	Kansas
United States	1160.128.1058 Boehringer Ingelheim Investigational Site	Pensacola	Florida
United States	1160.128.1056 Boehringer Ingelheim Investigational Site	Pittsburgh	Pennsylvania
United States	1160.128.1007 Boehringer Ingelheim Investigational Site	Port Charlotte	Florida
United States	1160.128.1001 Boehringer Ingelheim Investigational Site	Poughkeepsie	New York
United States	1160.128.1040 Boehringer Ingelheim Investigational Site	Rapid City	South Dakota
United States	1160.128.1015 Boehringer Ingelheim Investigational Site	Rochester Hills	Michigan
United States	1160.128.1060 Boehringer Ingelheim Investigational Site	Rockledge	Florida
United States	1160.128.1068 Boehringer Ingelheim Investigational Site	Roswell	Georgia
United States	1160.128.1012 Boehringer Ingelheim Investigational Site	Salisbury	Maryland
United States	1160.128.1082 Boehringer Ingelheim Investigational Site	San Antonio	Texas
United States	1160.128.1042 Boehringer Ingelheim Investigational Site	San Diego	California
United States	1160.128.1075 Boehringer Ingelheim Investigational Site	St. Louis	Missouri
United States	1160.128.1071 Boehringer Ingelheim Investigational Site	Statesville	North Carolina
United States	1160.128.1004 Boehringer Ingelheim Investigational Site	Tupelo	Mississippi
United States	1160.128.1065 Boehringer Ingelheim Investigational Site	Uniontown	Pennsylvania
United States	1160.128.1085 Boehringer Ingelheim Investigational Site	Washington	District of Columbia
United States	1160.128.1057 Boehringer Ingelheim Investigational Site	Waterbury	Connecticut
United States	1160.128.1048 Boehringer Ingelheim Investigational Site	Winfield	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	Week 4	No
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.	Week 4	No
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.	Week 4	No
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.	Week 8	No
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.	Week 8	No
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.; 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.	Week 8	No
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.	Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7 & Week 8	No
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.	Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7 & Week 8	No
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.	Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7 & Week 8	No
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.	Week 8	No

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