Clinical trial NCT01493557: 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
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Atrial Fibrillation
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2011-12-16
Enrollment: 1067
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.


Eligibility criteria: 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. not applicable
4. Contraindication to pantoprazole or other proton pump inhibitors, e.g. omeprazole, lansoprazole, rabeprazole, atnoprazole, esomeprazole
5. Contraindication to Pradaxa® (dabigatran etexilate) or known hypersensitivity to Pradaxa® (dabigatran etexilate) or its excipients
6. Hemorrhagic disorder, bleeding diathesis or active pathological bleeding
7. Need for anticoagulant treatment for disorders other than atrial fibrillation
8. Current treatment with rifampin
9. Creatinine clearance \<15ml/min (in Canada, \<30ml/min), or patients on renal replacement therapy (dialysis)
10. 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.
11. Patients who have received an investigational drug in the past 30 days or are participating in another drug study
12. Patients considered unreliable by the investigator concerning the requirements for follow-up during the study
13. Any condition the investigator believes would not allow safe participation in the study
14. 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.

Primary outcomes:
measure: The Rate of Complete Effectiveness of Initial GIS Management Strategy
timeFrame: Week 4
Secondary outcomes:
measure: Rate of Partial Effectiveness of Initial GIS Management Strategies
timeFrame: Week 4
measure: Combined Rate of Complete or Partial Effectiveness of Initial GIS Management Strategies
timeFrame: Week 4
measure: Rate of Complete Effectiveness of Combined GIS Management Strategies
timeFrame: Week 8
measure: Rate of Partial Effectiveness of Combined GIS Management Strategies
timeFrame: Week 8
measure: Combined Rate of Complete or Partial Effectiveness of Combined GIS Management Strategies
timeFrame: Week 8
measure: Rates of Complete Effectiveness of GIS at Each Visit.
timeFrame: Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7 & Week 8
measure: Rates of Partial Effectiveness of GIS at Each Visit.
timeFrame: Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7 & Week 8
measure: Rates of Complete or Partial Effectiveness of GIS at Each Visit.
timeFrame: Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7 & Week 8
measure: Time Between Symptom Onset and First Observed Complete or Partial Effectiveness and Between Symptom Onset and Last Observed Symptom
timeFrame: Week 8
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: 1160.128.1046 Boehringer Ingelheim Investigational Site
state: Alabama
city: Huntsville
country: United States
facility: 1160.128.1045 Boehringer Ingelheim Investigational Site
state: Alabama
city: Mobile
country: United States
facility: 1160.128.1003 Boehringer Ingelheim Investigational Site
state: Alabama
city: Chandler
country: United States
facility: 1160.128.1093 Boehringer Ingelheim Investigational Site
state: Arizona
city: Hot Springs
country: United States
facility: 1160.128.1067 Boehringer Ingelheim Investigational Site
state: Arkansas
city: Mesa
country: United States
facility: 1160.128.1103 Boehringer Ingelheim Investigational Site
state: California
city: Newport Beach
country: United States
facility: 1160.128.1094 Boehringer Ingelheim Investigational Site
state: California
city: San Diego
country: United States
facility: 1160.128.1042 Boehringer Ingelheim Investigational Site
state: California
city: Colorado Spring
country: United States
facility: 1160.128.1005 Boehringer Ingelheim Investigational Site
state: Colorado
city: Denver
country: United States
facility: 1160.128.1023 Boehringer Ingelheim Investigational Site
state: Colorado
city: Bridgeport
country: United States
facility: 1160.128.1016 Boehringer Ingelheim Investigational Site
state: Connecticut
city: Bridgeport
country: United States
facility: 1160.128.1066 Boehringer Ingelheim Investigational Site
state: Connecticut
city: Guilford
country: United States
facility: 1160.128.1018 Boehringer Ingelheim Investigational Site
state: Connecticut
city: Norwalk
country: United States
facility: 1160.128.1050 Boehringer Ingelheim Investigational Site
state: Connecticut
city: Waterbury
country: United States
facility: 1160.128.1057 Boehringer Ingelheim Investigational Site
state: Connecticut
city: Washington
country: United States
facility: 1160.128.1085 Boehringer Ingelheim Investigational Site
state: District of Columbia
city: Atlantis
country: United States
facility: 1160.128.1111 Boehringer Ingelheim Investigational Site
state: Florida
city: Brandon
country: United States
facility: 1160.128.1032 Boehringer Ingelheim Investigational Site
state: Florida
city: Coral Springs
country: United States
facility: 1160.128.1021 Boehringer Ingelheim Investigational Site
state: Florida
city: Daytona Beach
country: United States
facility: 1160.128.1027 Boehringer Ingelheim Investigational Site
state: Florida
city: Jacksonville
country: United States
facility: 1160.128.1019 Boehringer Ingelheim Investigational Site
state: Florida
city: Jacksonville
country: United States
facility: 1160.128.1062 Boehringer Ingelheim Investigational Site
state: Florida
city: Largo
country: United States
facility: 1160.128.1054 Boehringer Ingelheim Investigational Site
state: Florida
city: Miami
country: United States
facility: 1160.128.1097 Boehringer Ingelheim Investigational Site
state: Florida
city: Miami
country: United States
facility: 1160.128.1109 Boehringer Ingelheim Investigational Site
state: Florida
city: Orlando
country: United States
facility: 1160.128.1087 Boehringer Ingelheim Investigational Site
state: Florida
city: Pensacola
country: United States
facility: 1160.128.1058 Boehringer Ingelheim Investigational Site
state: Florida
city: Port Charlotte
country: United States
facility: 1160.128.1007 Boehringer Ingelheim Investigational Site
state: Florida
city: Rockledge
country: United States
facility: 1160.128.1060 Boehringer Ingelheim Investigational Site
state: Florida
city: Columbus
country: United States
facility: 1160.128.1096 Boehringer Ingelheim Investigational Site
state: Georgia
city: Roswell
country: United States
facility: 1160.128.1068 Boehringer Ingelheim Investigational Site
state: Georgia
city: Coeur d' Alene
country: United States
facility: 1160.128.1076 Boehringer Ingelheim Investigational Site
state: Idaho
city: Melrose Park
country: United States
facility: 1160.128.1073 Boehringer Ingelheim Investigational Site
state: Illinois
city: Winfield
country: United States
facility: 1160.128.1048 Boehringer Ingelheim Investigational Site
state: Illinois
city: Hammond
country: United States
facility: 1160.128.1105 Boehringer Ingelheim Investigational Site
state: Indiana
city: Indianapolis
country: United States
facility: 1160.128.1029 Boehringer Ingelheim Investigational Site
state: Indiana
city: Overland Park
country: United States
facility: 1160.128.1079 Boehringer Ingelheim Investigational Site
state: Kansas
city: Baton Rouge
country: United States
facility: 1160.128.1008 Boehringer Ingelheim Investigational Site
state: Louisiana
city: Auburn
country: United States
facility: 1160.128.1025 Boehringer Ingelheim Investigational Site
state: Maine
city: Biddeford
country: United States
facility: 1160.128.1100 Boehringer Ingelheim Investigational Site
state: Maine
city: Columbia
country: United States
facility: 1160.128.1041 Boehringer Ingelheim Investigational Site
state: Maryland
city: Salisbury
country: United States
facility: 1160.128.1012 Boehringer Ingelheim Investigational Site
state: Maryland
city: Rochester Hills
country: United States
facility: 1160.128.1015 Boehringer Ingelheim Investigational Site
state: Michigan
city: Tupelo
country: United States
facility: 1160.128.1004 Boehringer Ingelheim Investigational Site
state: Mississippi
city: Columbia
country: United States
facility: 1160.128.1014 Boehringer Ingelheim Investigational Site
state: Missouri
city: Kansas City
country: United States
facility: 1160.128.1047 Boehringer Ingelheim Investigational Site
state: Missouri
city: St. Louis
country: United States
facility: 1160.128.1075 Boehringer Ingelheim Investigational Site
state: Missouri
city: Great Falls
country: United States
facility: 1160.128.1069 Boehringer Ingelheim Investigational Site
state: Montana
city: Kalispell
country: United States
facility: 1160.128.1011 Boehringer Ingelheim Investigational Site
state: Montana
city: Lincoln
country: United States
facility: 1160.128.1092 Boehringer Ingelheim Investigational Site
state: Nebraska
city: Omaha
country: United States
facility: 1160.128.1059 Boehringer Ingelheim Investigational Site
state: Nebraska
city: Elmer
country: United States
facility: 1160.128.1039 Boehringer Ingelheim Investigational Site
state: New Jersey
city: Flemington
country: United States
facility: 1160.128.1035 Boehringer Ingelheim Investigational Site
state: New Jersey
city: Albuquerque
country: United States
facility: 1160.128.1036 Boehringer Ingelheim Investigational Site
state: New Mexico
city: Hawthorne
country: United States
facility: 1160.128.1063 Boehringer Ingelheim Investigational Site
state: New York
city: Mineola
country: United States
facility: 1160.128.1078 Boehringer Ingelheim Investigational Site
state: New York
city: Poughkeepsie
country: United States
facility: 1160.128.1001 Boehringer Ingelheim Investigational Site
state: New York
city: Asheville
country: United States
facility: 1160.128.1022 Boehringer Ingelheim Investigational Site
state: North Carolina
city: Gastonia
country: United States
facility: 1160.128.1052 Boehringer Ingelheim Investigational Site
state: North Carolina
city: Statesville
country: United States
facility: 1160.128.1071 Boehringer Ingelheim Investigational Site
state: North Carolina
city: Gallipolis
country: United States
facility: 1160.128.1091 Boehringer Ingelheim Investigational Site
state: Ohio
city: Oklahoma City
country: United States
facility: 1160.128.1107 Boehringer Ingelheim Investigational Site
state: Oklahoma
city: Bend
country: United States
facility: 1160.128.1053 Boehringer Ingelheim Investigational Site
state: Oregon
city: Hillsboro
country: United States
facility: 1160.128.1033 Boehringer Ingelheim Investigational Site
state: Oregon
city: Altoona
country: United States
facility: 1160.128.1037 Boehringer Ingelheim Investigational Site
state: Pennsylvania
city: Camp Hill
country: United States
facility: 1160.128.1034 Boehringer Ingelheim Investigational Site
state: Pennsylvania
city: Langhorne
country: United States
facility: 1160.128.1010 Boehringer Ingelheim Investigational Site
state: Pennsylvania
city: Pittsburgh
country: United States
facility: 1160.128.1056 Boehringer Ingelheim Investigational Site
state: Pennsylvania
city: Uniontown
country: United States
facility: 1160.128.1065 Boehringer Ingelheim Investigational Site
state: Pennsylvania
city: Charleston
country: United States
facility: 1160.128.1043 Boehringer Ingelheim Investigational Site
state: South Carolina
city: Rapid City
country: United States
facility: 1160.128.1040 Boehringer Ingelheim Investigational Site
state: South Dakota
city: Austin
country: United States
facility: 1160.128.1006 Boehringer Ingelheim Investigational Site
state: Texas
city: Houston
country: United States
facility: 1160.128.1104 Boehringer Ingelheim Investigational Site
state: Texas
city: McKinney
country: United States
facility: 1160.128.1061 Boehringer Ingelheim Investigational Site
state: Texas
city: New Braunfels
country: United States
facility: 1160.128.1090 Boehringer Ingelheim Investigational Site
state: Texas
city: San Antonio
country: United States
facility: 1160.128.1082 Boehringer Ingelheim Investigational Site
state: Texas
city: Layton
country: United States
facility: 1160.128.1102 Boehringer Ingelheim Investigational Site
state: Utah
city: Danville
country: United States
facility: 1160.128.1077 Boehringer Ingelheim Investigational Site
state: Virginia
city: Falls Church
country: United States
facility: 1160.128.1064 Boehringer Ingelheim Investigational Site
state: Virginia
city: Manassas
country: United States
facility: 1160.128.1110 Boehringer Ingelheim Investigational Site
state: Virginia
city: Norfolk
country: United States
facility: 1160.128.1099 Boehringer Ingelheim Investigational Site
state: Virginia
city: Calgary
country: Canada
facility: 1160.128.1160 Boehringer Ingelheim Investigational Site
state: Alberta
city: Edmonton
country: Canada
facility: 1160.128.1159 Boehringer Ingelheim Investigational Site
state: Alberta
city: Red Deer
country: Canada
facility: 1160.128.1152 Boehringer Ingelheim Investigational Site
state: Alberta
city: Spruce Grove
country: Canada
facility: 1160.128.1153 Boehringer Ingelheim Investigational Site
state: Alberta
city: Coquitlam
country: Canada
facility: 1160.128.1167 Boehringer Ingelheim Investigational Site
state: British Columbia
city: Victoria
country: Canada
facility: 1160.128.1158 Boehringer Ingelheim Investigational Site
state: British Columbia
city: Saint John
country: Canada
facility: 1160.128.1154 Boehringer Ingelheim Investigational Site
state: New Brunswick
city: Bay Roberts
country: Canada
facility: 1160.128.1166 Boehringer Ingelheim Investigational Site
state: Newfoundland and Labrador
city: Brampton
country: Canada
facility: 1160.128.1151 Boehringer Ingelheim Investigational Site
state: Ontario
city: Cambridge
country: Canada
facility: 1160.128.1168 Boehringer Ingelheim Investigational Site
state: Ontario
city: Collingwood
country: Canada
facility: 1160.128.1164 Boehringer Ingelheim Investigational Site
state: Ontario
city: Corunna
country: Canada
facility: 1160.128.1173 Boehringer Ingelheim Investigational Site
state: Ontario
city: Hamilton
country: Canada
facility: 1160.128.1156 Boehringer Ingelheim Investigational Site
state: Ontario
city: Kitchener
country: Canada
facility: 1160.128.1157 Boehringer Ingelheim Investigational Site
state: Ontario
city: London
country: Canada
facility: 1160.128.1155 Boehringer Ingelheim Investigational Site
state: Ontario
city: Peterborough
country: Canada
facility: 1160.128.1170 Boehringer Ingelheim Investigational Site
state: Ontario
city: Sarnia
country: Canada
facility: 1160.128.1165 Boehringer Ingelheim Investigational Site
state: Ontario
city: Sarnia
country: Canada
facility: 1160.128.1169 Boehringer Ingelheim Investigational Site
state: Ontario
city: Stayner
country: Canada
facility: 1160.128.1161 Boehringer Ingelheim Investigational Site
state: Ontario
city: Sudbury
country: Canada
facility: 1160.128.1171 Boehringer Ingelheim Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: 1160.128.1162 Boehringer Ingelheim Investigational Site
state: Ontario
city: Saskatoon
country: Canada
facility: 1160.128.1172 Boehringer Ingelheim Investigational Site
state: Saskatchewan
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: 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.