Testing Platelet Reactivity In Patients Undergoing Elective Stent Placement on Clopidogrel to Guide Alternative Therapy With Prasugrel (TRIGGER-PCI)

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00910299
• Collaborator: Daiichi Sankyo Co., Ltd. (Industry)
• Enrollment: 423
• Locations: 27
• Arms: 2
• Duration (Months): 21
• Patients Per Site: 15.7
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

To determine the efficacy of prasugrel versus clopidogrel for the reduction of adverse cardiovascular outcomes in patients with high platelet reactivity on clopidogrel after successful implantation of coronary drug-eluting stents.

To determine the adverse event profile of prasugrel in patients with high platelet reactivity on clopidogrel after implantation of coronary drug-eluting stents.

To determine the effect of prasugrel on inhibition of platelet activation in patients with high platelet reactivity on clopidogrel.

Condition or Disease	Intervention/Treatment	Phase
Coronary Artery Disease (CAD)	Drug: Prasugrel; Drug: Clopidogrel	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 423 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Effectiveness of Prasugrel Versus Clopidogrel in Subjects With High Platelet Reactivity on Clopidogrel Following Elective Percutaneous Coronary Intervention With Implantation of Drug-Eluting Stent
• Study Start Date: Jul 1, 2009
• Actual Primary Completion Date: Apr 1, 2011
• Actual Study Completion Date: Apr 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Prasugrel	Drug: Prasugrel; One time 60 milligram (mg) oral loading dose and 10 mg once daily oral maintenance dose up to 6 months.; Other Names: LY640315 Effient Efient
Active Comparator: Clopidogrel	Drug: Clopidogrel; 75 mg oral daily maintenance dose up to 6 months.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Composite Endpoint of Cardiovascular Death or Myocardial Infarction (MI) [Baseline through 6 months]

   The endpoint in this measure is a combination of cardiovascular death or MI.

Secondary Outcome Measures

1. Number of Participants With Stent Thrombosis (ST) [Baseline through 6 months]

   Academic Research Consortium (ARC) criteria was used to define ST. Definite ST is angiographic or pathologic confirmation of partial or total thrombotic occlusion within the peri-stent region, and at least one of the following additional criteria: acute ischemic symptoms; ischemic electrocardiogram changes; elevated cardiac biomarkers. Probable ST is any unexplained death within 30 days of stent implantation; any MI, which is related to documented acute ischemia in the territory of the implanted stent without angiographic confirmation of ST and in the absence of any other obvious cause.

2. Number of Participants With Composite Endpoint of All-Cause Death or Myocardial Infarction (MI) [Baseline through 6 months]

   The endpoint in this measure is a combination of all-cause death or MI.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

• Have coronary artery disease and clinical indication for percutaneous coronary intervention (PCI) with implantation of at least one drug-eluting stent and where percutaneous coronary intervention of all treated lesions is successful.

• Have been given standard-of-care clopidogrel 600-mg loading dose between 24 hours before and at the time of PCI.

• Standard of Care Aspirin use prior to PCI - at least 250-mg [intravenous (IV) or oral] within 24 hours before PCI and at the time of PCI.

• VerifyNow P2Y12 reaction units > 208 measured 2-7 hours after clopidogrel maintenance dose the day after successful PCI.

Exclusion Criteria:

• Non-ST segment elevation myocardial infarction within 14 days prior to randomization

• ST-segment elevation myocardial infarction within 14 days prior to randomization

• Have known major complications after percutaneous coronary intervention and prior to randomization

• Have a body weight < 60 kilogram (kg)

• Have cardiogenic shock at time of randomization

• Have refractory ventricular arrhythmias

• Have New York Heart Association Class IV congestive heart failure

• Have received glycoprotein (GP) IIb/IIIa inhibitors eptifibatide or tirofiban within 24 hrs before or during percutaneous coronary intervention or abciximab within 10 days before or during percutaneous coronary intervention

• Are receiving daily treatment with nonsteroidal anti-inflammatory drug (NSAIDs) or cyclooxygenase-2 (COX2) inhibitors that cannot be discontinued or are anticipated to require > 2 weeks of daily treatment during the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Clearwater	Florida	United States	33756
2	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Jacksonville	Florida	United States	32209
3	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Rome	Georgia	United States	30165
4	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Moline	Illinois	United States	61265
5	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	New York	New York	United States	10021
6	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Portland	Oregon	United States	97225
7	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Pittsburgh	Pennsylvania	United States	15213
8	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Rapid City	South Dakota	United States	55701
9	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Nashville	Tennessee	United States	37203
10	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Bad Berka		Germany	99437
11	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Bad Krozingen		Germany	79189
12	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Bad Segeberg		Germany	23795
13	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Berlin		Germany	12203
14	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Bremen		Germany	28277
15	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Dortmund		Germany	44137
16	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Essen		Germany	45147
17	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Freiburg		Germany	79106
18	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Fulda		Germany	36043
19	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Hamburg		Germany	20246
20	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Leipzig		Germany	04289
21	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Mainz		Germany	55131
22	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Munich		Germany	80636
23	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Pforzheim		Germany	75175
24	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Stuttgart		Germany	70376
25	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Tuebingen		Germany	72076
26	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Villingen-Schwenningen		Germany	78050
27	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Wuppertal		Germany	42117

Sponsors and Collaborators

• Eli Lilly and Company
• Daiichi Sankyo Co., Ltd.

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT00910299
• Other Study ID Numbers: 12323; H7T-MC-TACW
• First Posted: May 29, 2009
• Last Update Posted: Jun 8, 2012
• Last Verified: Apr 1, 2012

• Keywords provided by Eli Lilly and Company: Clopidogrel; VerifyNow; PRU Measurements; Drug Eluting Stents (DES); Heart Disease; Percutaneous Coronary Intervention (PCI); P2Y12; Platelets; Platelet Reactivity
• Additional relevant MeSH terms: Coronary Artery Disease; Clopidogrel; Prasugrel Hydrochloride

Study Results

Participant Flow

Arm/Group Title	Prasugrel	Clopidogrel
Arm/Group Description	One time 60 milligram (mg) oral loading dose and 10 mg once daily oral maintenance dose up to 6 months	75 mg oral daily maintenance dose up to 6 months.
Period Title: Overall Study
STARTED	212	211
Received at Least 1 Dose of Study Drug	210	210
COMPLETED	136	137
NOT COMPLETED	76	74

Baseline Characteristics

Arm/Group Title	Prasugrel	Clopidogrel	Total
Arm/Group Description	One time 60 milligram (mg) oral loading dose and 10 mg once daily oral maintenance dose up to 6 months	75 mg oral daily maintenance dose up to 6 months.	Total of all reporting groups
Overall Participants	212	211	423
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	65.8 (8.3)	66.3 (8.6)	66.1 (8.4)
Sex: Female, Male (Count of Participants)
Female	59 27.8%	57 27%	116 27.4%
Male	153 72.2%	154 73%	307 72.6%
Race/Ethnicity, Customized (participants) [Number]
Asian	1 0.5%	1 0.5%	2 0.5%
Black or African American	0 0%	3 1.4%	3 0.7%
White	211 99.5%	207 98.1%	418 98.8%
Region of Enrollment (participants) [Number]
United States	12 5.7%	13 6.2%	25 5.9%
Germany	200 94.3%	198 93.8%	398 94.1%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Composite Endpoint of Cardiovascular Death or Myocardial Infarction (MI)
Description	The endpoint in this measure is a combination of cardiovascular death or MI.
Time Frame	Baseline through 6 months

Outcome Measure Data

Analysis Population Description

Participants who were randomized.

Arm/Group Title	Prasugrel	Clopidogrel
Arm/Group Description	One time 60 milligram (mg) oral loading dose and 10 mg once daily oral maintenance dose up to 6 months	75 mg oral daily maintenance dose up to 6 months.
Measure Participants	212	211
Number [participants]	0 0%	1 0.5%

2. Secondary Outcome

Title	Number of Participants With Stent Thrombosis (ST)
Description	Academic Research Consortium (ARC) criteria was used to define ST. Definite ST is angiographic or pathologic confirmation of partial or total thrombotic occlusion within the peri-stent region, and at least one of the following additional criteria: acute ischemic symptoms; ischemic electrocardiogram changes; elevated cardiac biomarkers. Probable ST is any unexplained death within 30 days of stent implantation; any MI, which is related to documented acute ischemia in the territory of the implanted stent without angiographic confirmation of ST and in the absence of any other obvious cause.
Time Frame	Baseline through 6 months

Outcome Measure Data

Analysis Population Description

Participants who were randomized.

Arm/Group Title	Prasugrel	Clopidogrel
Arm/Group Description	One time 60 milligram (mg) oral loading dose and 10 mg once daily oral maintenance dose up to 6 months	75 mg oral daily maintenance dose up to 6 months.
Measure Participants	212	211
Number [participants]	0 0%	0 0%

3. Secondary Outcome

Title	Number of Participants With Composite Endpoint of All-Cause Death or Myocardial Infarction (MI)
Description	The endpoint in this measure is a combination of all-cause death or MI.
Time Frame	Baseline through 6 months

Outcome Measure Data

Analysis Population Description

Participants who were randomized.

Arm/Group Title	Prasugrel	Clopidogrel
Arm/Group Description	One time 60 milligram (mg) oral loading dose and 10 mg once daily oral maintenance dose up to 6 months	75 mg oral daily maintenance dose up to 6 months.
Measure Participants	212	211
Number [participants]	0 0%	2 0.9%

Adverse Events

Arm/Group Title	Prasugrel		Clopidogrel
Arm/Group Description	One time 60 milligram (mg) oral loading dose and 10 mg once daily oral maintenance dose up to 6 months		75 mg oral daily maintenance dose up to 6 months.
All Cause Mortality
	Prasugrel		Clopidogrel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Prasugrel		Clopidogrel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	40/210 (19%)		38/210 (18.1%)
Cardiac disorders
Angina pectoris	6/210 (2.9%)	6	2/210 (1%)	2
Angina unstable	0/210 (0%)	0	1/210 (0.5%)	1
Arrhythmia	1/210 (0.5%)	1	0/210 (0%)	0
Atrial fibrillation	0/210 (0%)	0	1/210 (0.5%)	1
Atrioventricular block second degree	0/210 (0%)	0	1/210 (0.5%)	1
Bradycardia	1/210 (0.5%)	1	0/210 (0%)	0
Cardiac failure	1/210 (0.5%)	1	2/210 (1%)	2
Cardiac failure acute	0/210 (0%)	0	1/210 (0.5%)	1
Cardiac failure congestive	0/210 (0%)	0	1/210 (0.5%)	1
Coronary artery stenosis	1/210 (0.5%)	1	0/210 (0%)	0
Mitral valve incompetence	0/210 (0%)	0	1/210 (0.5%)	1
Pericardial effusion	1/210 (0.5%)	1	0/210 (0%)	0
Ventricular tachycardia	0/210 (0%)	0	1/210 (0.5%)	1
Ear and labyrinth disorders
Deafness	1/210 (0.5%)	1	0/210 (0%)	0
Gastrointestinal disorders
Gastric ulcer	1/210 (0.5%)	1	0/210 (0%)	0
Gastritis	0/210 (0%)	0	1/210 (0.5%)	1
Gastritis erosive	0/210 (0%)	0	1/210 (0.5%)	1
Gastrointestinal haemorrhage	1/210 (0.5%)	1	1/210 (0.5%)	1
Melaena	0/210 (0%)	0	1/210 (0.5%)	1
Rectal haemorrhage	1/210 (0.5%)	1	1/210 (0.5%)	1
Vomiting	0/210 (0%)	0	1/210 (0.5%)	1
General disorders
Catheter site haemorrhage	1/210 (0.5%)	1	0/210 (0%)	0
Chest pain	1/210 (0.5%)	1	0/210 (0%)	0
Non-cardiac chest pain	2/210 (1%)	2	5/210 (2.4%)	5
Infections and infestations
Arthritis infective	1/210 (0.5%)	1	0/210 (0%)	0
Bronchitis	1/210 (0.5%)	1	0/210 (0%)	0
Cellulitis	1/210 (0.5%)	1	0/210 (0%)	0
Clostridium difficile colitis	0/210 (0%)	0	1/210 (0.5%)	2
Diverticulitis	0/210 (0%)	0	1/210 (0.5%)	1
Erysipelas	1/210 (0.5%)	1	0/210 (0%)	0
Gastroenteritis norovirus	1/210 (0.5%)	1	0/210 (0%)	0
Nasopharyngitis	0/210 (0%)	0	1/210 (0.5%)	1
Sepsis	0/210 (0%)	0	1/210 (0.5%)	1
Viral infection	0/210 (0%)	0	1/210 (0.5%)	1
Injury, poisoning and procedural complications
Contusion	0/210 (0%)	0	2/210 (1%)	2
In-stent coronary artery restenosis	0/210 (0%)	0	1/210 (0.5%)	1
Spinal compression fracture	0/210 (0%)	0	1/210 (0.5%)	1
Vascular pseudoaneurysm	1/210 (0.5%)	1	1/210 (0.5%)	1
Investigations
Blood creatine phosphokinase increased	0/210 (0%)	0	1/210 (0.5%)	1
Blood creatinine increased	1/210 (0.5%)	1	0/210 (0%)	0
Troponin increased	0/210 (0%)	0	1/210 (0.5%)	1
Metabolism and nutrition disorders
Hyperglycaemia	0/210 (0%)	0	1/210 (0.5%)	1
Musculoskeletal and connective tissue disorders
Gouty arthritis	1/210 (0.5%)	1	0/210 (0%)	0
Intervertebral disc protrusion	1/210 (0.5%)	1	0/210 (0%)	0
Musculoskeletal chest pain	1/210 (0.5%)	1	1/210 (0.5%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute lymphocytic leukaemia	1/210 (0.5%)	1	0/210 (0%)	0
Burkitt's lymphoma	1/210 (0.5%)	1	0/210 (0%)	0
Oropharyngeal cancer stage unspecified	0/210 (0%)	0	1/210 (0.5%)	1
Ovarian adenoma	1/210 (0.5%)	1	0/210 (0%)	0
Nervous system disorders
Hypoglycaemic coma	1/210 (0.5%)	1	0/210 (0%)	0
Ischaemic stroke	0/210 (0%)	0	1/210 (0.5%)	1
Neuralgia	0/210 (0%)	0	1/210 (0.5%)	1
Syncope	1/210 (0.5%)	1	0/210 (0%)	0
Transient ischaemic attack	0/210 (0%)	0	1/210 (0.5%)	1
Psychiatric disorders
Alcohol abuse	0/210 (0%)	0	1/210 (0.5%)	1
Depression	0/210 (0%)	0	1/210 (0.5%)	2
Panic attack	1/210 (0.5%)	1	0/210 (0%)	0
Renal and urinary disorders
Renal impairment	1/210 (0.5%)	1	0/210 (0%)	0
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	1/210 (0.5%)	2	0/210 (0%)	0
Dyspnoea	1/210 (0.5%)	1	0/210 (0%)	0
Dyspnoea exertional	1/210 (0.5%)	1	0/210 (0%)	0
Pleural effusion	0/210 (0%)	0	1/210 (0.5%)	1
Skin and subcutaneous tissue disorders
Rash	0/210 (0%)	0	1/210 (0.5%)	1
Surgical and medical procedures
Coronary revascularisation	0/210 (0%)	0	1/210 (0.5%)	1
Percutaneous coronary intervention	1/210 (0.5%)	1	0/210 (0%)	0
Vascular disorders
Aortic aneurysm	0/210 (0%)	0	2/210 (1%)	2
Deep vein thrombosis	1/210 (0.5%)	1	0/210 (0%)	0
Hypertension	1/210 (0.5%)	1	0/210 (0%)	0
Hypertensive crisis	3/210 (1.4%)	3	2/210 (1%)	2
Intermittent claudication	1/210 (0.5%)	2	0/210 (0%)	0
Peripheral arterial occlusive disease	0/210 (0%)	0	1/210 (0.5%)	1
Peripheral artery aneurysm	0/210 (0%)	0	1/210 (0.5%)	1
Other (Not Including Serious) Adverse Events
	Prasugrel		Clopidogrel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	110/210 (52.4%)		72/210 (34.3%)
Blood and lymphatic system disorders
Anaemia	1/210 (0.5%)	1	0/210 (0%)	0
Spontaneous haematoma	6/210 (2.9%)	6	2/210 (1%)	2
Cardiac disorders
Angina pectoris	2/210 (1%)	2	1/210 (0.5%)	1
Atrial fibrillation	2/210 (1%)	2	3/210 (1.4%)	3
Bradycardia	1/210 (0.5%)	1	0/210 (0%)	0
Bundle branch block left	1/210 (0.5%)	1	0/210 (0%)	0
Cardiac failure chronic	0/210 (0%)	0	1/210 (0.5%)	1
Coronary artery disease	0/210 (0%)	0	2/210 (1%)	2
Intracardiac thrombus	0/210 (0%)	0	1/210 (0.5%)	1
Myocardial infarction	2/210 (1%)	2	0/210 (0%)	0
Ventricular extrasystoles	0/210 (0%)	0	1/210 (0.5%)	1
Ear and labyrinth disorders
Vertigo	1/210 (0.5%)	1	2/210 (1%)	2
Eye disorders
Conjunctival haemorrhage	1/210 (0.5%)	1	0/210 (0%)	0
Conjunctivitis	1/210 (0.5%)	1	0/210 (0%)	0
Glaucoma	1/210 (0.5%)	1	0/210 (0%)	0
Gastrointestinal disorders
Abdominal pain	1/210 (0.5%)	1	0/210 (0%)	0
Abdominal pain upper	0/210 (0%)	0	1/210 (0.5%)	2
Constipation	0/210 (0%)	0	1/210 (0.5%)	1
Diarrhoea	3/210 (1.4%)	3	6/210 (2.9%)	6
Faeces discoloured	1/210 (0.5%)	1	0/210 (0%)	0
Gastritis	1/210 (0.5%)	1	1/210 (0.5%)	2
Gastrointestinal disorder	0/210 (0%)	0	1/210 (0.5%)	1
Gastrooesophageal reflux disease	0/210 (0%)	0	1/210 (0.5%)	1
Gingivitis	1/210 (0.5%)	1	1/210 (0.5%)	1
Haematochezia	0/210 (0%)	0	1/210 (0.5%)	1
Haemorrhoidal haemorrhage	1/210 (0.5%)	1	0/210 (0%)	0
Nausea	2/210 (1%)	2	3/210 (1.4%)	3
Periodontitis	0/210 (0%)	0	1/210 (0.5%)	1
Vomiting	1/210 (0.5%)	1	0/210 (0%)	0
General disorders
Chest pain	0/210 (0%)	0	1/210 (0.5%)	1
Fatigue	2/210 (1%)	2	1/210 (0.5%)	1
Non-cardiac chest pain	0/210 (0%)	0	2/210 (1%)	2
Oedema due to cardiac disease	1/210 (0.5%)	1	0/210 (0%)	0
Oedema peripheral	3/210 (1.4%)	3	2/210 (1%)	2
Vessel puncture site haematoma	1/210 (0.5%)	1	0/210 (0%)	0
Immune system disorders
Seasonal allergy	1/210 (0.5%)	1	0/210 (0%)	0
Infections and infestations
Acute tonsillitis	1/210 (0.5%)	1	0/210 (0%)	0
Bronchitis	3/210 (1.4%)	4	2/210 (1%)	2
Cystitis	2/210 (1%)	2	1/210 (0.5%)	1
Diverticulitis	1/210 (0.5%)	1	0/210 (0%)	0
Erysipelas	2/210 (1%)	2	0/210 (0%)	0
Furuncle	3/210 (1.4%)	3	0/210 (0%)	0
Gastrointestinal infection	1/210 (0.5%)	1	3/210 (1.4%)	3
Nasopharyngitis	15/210 (7.1%)	18	8/210 (3.8%)	8
Onychomycosis	1/210 (0.5%)	1	0/210 (0%)	0
Oral herpes	1/210 (0.5%)	1	0/210 (0%)	0
Otitis externa	0/210 (0%)	0	1/210 (0.5%)	1
Pneumonia	0/210 (0%)	0	1/210 (0.5%)	1
Upper respiratory tract infection	1/210 (0.5%)	1	0/210 (0%)	0
Urinary tract infection	1/210 (0.5%)	1	1/210 (0.5%)	1
Injury, poisoning and procedural complications
Arthropod bite	0/210 (0%)	0	1/210 (0.5%)	1
Contusion	7/210 (3.3%)	7	2/210 (1%)	2
Foot fracture	1/210 (0.5%)	1	0/210 (0%)	0
Joint capsule rupture	0/210 (0%)	0	1/210 (0.5%)	1
Joint sprain	3/210 (1.4%)	3	0/210 (0%)	0
Muscle strain	0/210 (0%)	0	1/210 (0.5%)	1
Periorbital haematoma	1/210 (0.5%)	1	1/210 (0.5%)	1
Post procedural haematoma	1/210 (0.5%)	1	0/210 (0%)	0
Skin laceration	0/210 (0%)	0	1/210 (0.5%)	1
Traumatic haematoma	4/210 (1.9%)	4	4/210 (1.9%)	4
Vascular pseudoaneurysm	2/210 (1%)	2	0/210 (0%)	0
Investigations
Arteriogram coronary	0/210 (0%)	0	1/210 (0.5%)	1
Blood creatine increased	1/210 (0.5%)	1	0/210 (0%)	0
Blood creatine phosphokinase increased	0/210 (0%)	0	2/210 (1%)	2
Blood creatine phosphokinase mb increased	0/210 (0%)	0	1/210 (0.5%)	1
White blood cell count increased	0/210 (0%)	0	1/210 (0.5%)	1
Metabolism and nutrition disorders
Diabetes mellitus	0/210 (0%)	0	1/210 (0.5%)	1
Hypercholesterolaemia	1/210 (0.5%)	1	3/210 (1.4%)	3
Hyperkalaemia	1/210 (0.5%)	1	0/210 (0%)	0
Hyperlipidaemia	2/210 (1%)	2	0/210 (0%)	0
Hyperuricaemia	1/210 (0.5%)	1	0/210 (0%)	0
Hypokalaemia	1/210 (0.5%)	1	1/210 (0.5%)	1
Hypokalaemic syndrome	1/210 (0.5%)	1	0/210 (0%)	0
Obesity	0/210 (0%)	0	1/210 (0.5%)	1
Type 2 diabetes mellitus	1/210 (0.5%)	1	0/210 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	1/210 (0.5%)	1	1/210 (0.5%)	1
Arthritis	0/210 (0%)	0	2/210 (1%)	2
Back pain	2/210 (1%)	2	1/210 (0.5%)	1
Bursitis	0/210 (0%)	0	1/210 (0.5%)	1
Jaw cyst	1/210 (0.5%)	1	0/210 (0%)	0
Muscular weakness	0/210 (0%)	0	1/210 (0.5%)	1
Musculoskeletal chest pain	2/210 (1%)	2	0/210 (0%)	0
Musculoskeletal pain	1/210 (0.5%)	1	0/210 (0%)	0
Osteoarthritis	1/210 (0.5%)	1	0/210 (0%)	0
Pain in extremity	1/210 (0.5%)	1	0/210 (0%)	0
Rheumatic fever	0/210 (0%)	0	1/210 (0.5%)	1
Rheumatoid arthritis	1/210 (0.5%)	1	0/210 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Thyroid neoplasm	1/210 (0.5%)	1	0/210 (0%)	0
Nervous system disorders
Dizziness	1/210 (0.5%)	1	1/210 (0.5%)	1
Dizziness postural	0/210 (0%)	0	1/210 (0.5%)	1
Dysgeusia	1/210 (0.5%)	1	0/210 (0%)	0
Headache	1/210 (0.5%)	1	0/210 (0%)	0
Paraesthesia	1/210 (0.5%)	1	0/210 (0%)	0
Sciatica	1/210 (0.5%)	1	0/210 (0%)	0
Syncope	1/210 (0.5%)	1	0/210 (0%)	0
Psychiatric disorders
Anxiety disorder	1/210 (0.5%)	1	0/210 (0%)	0
Insomnia	1/210 (0.5%)	1	0/210 (0%)	0
Nightmare	1/210 (0.5%)	1	0/210 (0%)	0
Panic attack	1/210 (0.5%)	1	0/210 (0%)	0
Sleep disorder	1/210 (0.5%)	1	0/210 (0%)	0
Renal and urinary disorders
Renal failure chronic	1/210 (0.5%)	1	0/210 (0%)	0
Reproductive system and breast disorders
Benign prostatic hyperplasia	0/210 (0%)	0	1/210 (0.5%)	1
Respiratory, thoracic and mediastinal disorders
Bronchospasm	0/210 (0%)	0	1/210 (0.5%)	1
Cough	1/210 (0.5%)	1	0/210 (0%)	0
Dyspnoea	3/210 (1.4%)	3	0/210 (0%)	0
Dyspnoea exertional	0/210 (0%)	0	1/210 (0.5%)	1
Epistaxis	20/210 (9.5%)	21	8/210 (3.8%)	10
Obstructive airways disorder	1/210 (0.5%)	1	0/210 (0%)	0
Pleural effusion	0/210 (0%)	0	1/210 (0.5%)	1
Skin and subcutaneous tissue disorders
Alopecia	1/210 (0.5%)	1	0/210 (0%)	0
Dermatitis	1/210 (0.5%)	1	0/210 (0%)	0
Drug eruption	0/210 (0%)	0	1/210 (0.5%)	1
Eczema	3/210 (1.4%)	3	3/210 (1.4%)	3
Erythema	1/210 (0.5%)	1	0/210 (0%)	0
Pruritus	6/210 (2.9%)	6	1/210 (0.5%)	1
Pruritus generalised	0/210 (0%)	0	2/210 (1%)	2
Rash	3/210 (1.4%)	3	1/210 (0.5%)	1
Rash generalised	0/210 (0%)	0	1/210 (0.5%)	1
Skin ulcer	0/210 (0%)	0	3/210 (1.4%)	3
Surgical and medical procedures
Cardiac pacemaker insertion	1/210 (0.5%)	1	0/210 (0%)	0
Implantable defibrillator insertion	1/210 (0.5%)	1	0/210 (0%)	0
Limb operation	0/210 (0%)	0	1/210 (0.5%)	1
Nasal septal operation	1/210 (0.5%)	1	0/210 (0%)	0
Percutaneous coronary intervention	2/210 (1%)	2	0/210 (0%)	0
Renal revascularisation surgery	1/210 (0.5%)	1	0/210 (0%)	0
Smoking cessation therapy	0/210 (0%)	0	1/210 (0.5%)	1
Tooth extraction	1/210 (0.5%)	1	0/210 (0%)	0
Vascular disorders
Haematoma	1/210 (0.5%)	1	0/210 (0%)	0
Hot flush	1/210 (0.5%)	1	0/210 (0%)	0
Hypertension	3/210 (1.4%)	3	2/210 (1%)	2
Hypotension	1/210 (0.5%)	1	0/210 (0%)	0
Peripheral arterial occlusive disease	1/210 (0.5%)	1	0/210 (0%)	0
Thrombophlebitis	1/210 (0.5%)	1	0/210 (0%)	0
Varicose vein	1/210 (0.5%)	1	0/210 (0%)	0

Limitations/Caveats

The study was terminated early, and no formal statistical time-to-event analysis was performed.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.