A-TREAT: American Trial Using Tranexamic Acid in Thrombocytopenia

• Sponsor: University of Washington (Other)
• Overall Status: Completed
• CT.gov ID: NCT02578901
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI) (NIH)
• Enrollment: 330
• Locations: 3
• Arms: 2
• Actual Duration (Months): 48.3
• Patients Per Site: 110
• Patients Per Site Per Month: 2.3

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the usefulness of antifibrinolytic therapy with tranexamic acid (TXA) in preventing bleeding in patients who are thrombocytopenic due to primary bone marrow disorders or chemotherapy, immunotherapy and/or radiation therapy.

Condition or Disease	Intervention/Treatment	Phase
Thrombocytopenia	Drug: Tranexamic Acid; Drug: Placebo	Phase 3

Detailed Description

The purpose of this study is to conduct a prospective, randomized, blinded, placebo controlled trial to evaluate the usefulness of antifibrinolytic therapy with tranexamic acid in preventing bleeding in patients who are thrombocytopenic due to primary bone marrow disorders or chemotherapy, immunotherapy and/or radiation therapy. The results of this study will change practice by providing evidence as to whether or not TXA is effective and safe treatment when used as an adjunct to platelet transfusion therapy in the thrombocytopenic patient.

Study Design

• Study Type: Interventional
• Actual Enrollment: 330 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: American Trial Using Tranexamic Acid in Thrombocytopenia (A-TREAT)
• Actual Study Start Date: Jun 1, 2016
• Actual Primary Completion Date: Mar 1, 2020
• Actual Study Completion Date: Jun 11, 2020

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Tranexamic Acid (TXA) IV or PO administered after meeting inclusion/exclusion criteria	Drug: Tranexamic Acid; Doses will be given intravenous (IV) or orally (PO) per the discretion of the treating investigator. Doses are administered every 8 hours. When given IV, TXA 1.0 gram will be administered. When given PO, TXA 1.3 grams will be administered; Other Names: TXA
Placebo Comparator: Placebo IV Normal Saline or PO placebo pills administered after meeting inclusion/exclusion criteria	Drug: Placebo; Doses will be given intravenous (IV) or orally (PO) per the discretion of the treating investigator. Doses are administered every 8 hours. When given IV, Normal Saline will be administered. When given PO, placebo pills will be administered; Other Names: NS

Outcome Measures

Primary Outcome Measures

1. Bleeding Within 30 Days [30 days after activation of study drug]

   Proportion of patients with bleeding of WHO grade 2 or above, over the study period of 30 days after activation of study drug.

Secondary Outcome Measures

1. Number of Platelet Transfusions [30 days after activation of study drug]

   Number of platelet transfusions per patient during the first 30 days post prescription activation of study drug

2. Number of Days Alive and Without WHO Grade 2 Bleeding [during the first 30 days post activation of study drug]

   Number of days alive and without WHO grade 2 bleeding or greater during the first 30 days post activation of study drug

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria (all must be met):

• Must be ≥ 18 years of age

• Confirmed diagnosis of a hematologic malignancy or aplasia

• Undergoing or planned chemotherapy, immunotherapy, or hematopoietic stem cell transplantation

• Anticipated to have hypoproliferative thrombocytopenia resulting in a platelet count of ≤ 10,000/microliters for ≥ 5 days

• Able to provide informed consent and comply with treatment and monitoring, or having a Legally Authorized Representative (LAR)

Exclusion criteria (none can be present):

• Diagnosis of acute promyelocytic leukemia undergoing induction chemotherapy

• History of ITP, TTP or HUS

• Subjects receiving L-asparaginase as part of their current cycle of treatment

• Subjects with a past history or current diagnosis of arterial or venous thromboembolic disease including acute coronary syndrome, peripheral vascular disease and retinal arterial or venous thrombosis (except when a prior history of central line thrombosis has resolved)

• Subjects with a diagnosis/previous history of sinusoidal obstruction syndrome (also called veno-occlusive disease)

• Subjects receiving any pro-coagulant agents (e.g. DDAVP, recombinant Factor VIIa or Prothrombin Complex Concentrates (PCC) and/or an antifibrinolytic agent within 48 hours of enrollment, or with known hypercoagulable state

• Known inherited or acquired bleeding disorder including, but not limited to:

• Acquired storage pool deficiency

• Paraproteinemia with platelet inhibition

• Known inherited or acquired prothrombotic disorders, including antiphospholipid syndrome. Those with lupus anticoagulant or positive antiphospholipid serology without thrombosis are not excluded.

• Subjects receiving anticoagulant therapy or anti-platelet therapy (except when receiving prophylactic anticoagulant or low dose aspirin therapy for prophylaxis only with a plan to discontinue when the platelet count falls below 50,000)

• Patients with DIC according to the patient's physician

• Subjects with WHO Grade 2 bleeding or greater within 48 hours prior to activation

• Subjects requiring a platelet transfusion threshold > 10,000/microliters at time of randomization

• Subjects with anuria (defined as urine output < 10mls/hr over 24 hours)

• Subjects on dialysis

• Subjects with creatinine ≥5.7mg/dL

• Subjects who are pregnant or nursing or unwilling to use contraception during and for 30 days after taking the study drug (both males and females)

• Subjects enrolled in other trials involving platelet transfusions, anti-fibrinolytics, platelet growth factors or other pro-coagulant agents.

• Known allergy to tranexamic acid

• Having been previously randomized in this study at any stage of their treatment

• Subjects who are unwilling to accept blood or blood component transfusions

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of North Carolina	Chapel Hill	North Carolina	United States	21599
2	University of Pittsburgh	Pittsburgh	Pennsylvania	United States	15213
3	University of Washington	Seattle	Washington	United States	98195

Sponsors and Collaborators

• University of Washington
• National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Principal Investigator: Terry Gernsheimer, MD, University of Washington

Study Documents (Full-Text)

• Study Protocol - May 7, 2018
• Statistical Analysis Plan - Jun 3, 2019
• Informed Consent Form - Jun 24, 2016

More Information

Publications

None provided.

• Responsible Party: Susanne May, Professor, Biostatistics, University of Washington
• ClinicalTrials.gov Identifier: NCT02578901
• Other Study ID Numbers: STUDY00003329; 1U01HL122272-01A1
• First Posted: Oct 19, 2015
• Last Update Posted: Mar 24, 2021
• Last Verified: Feb 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Susanne May, Professor, Biostatistics, University of Washington: Thrombocytopenia; Tranexamic Acid; TXA; Chemotherapy induced thrombocytopenia
• Additional relevant MeSH terms: Thrombocytopenia; Tranexamic Acid

Study Results

Participant Flow

Arm/Group Title	Tranexamic Acid (TXA)	Placebo
Arm/Group Description	IV or PO administered after meeting inclusion/exclusion criteria Tranexamic Acid: Doses will be given intravenous (IV) or orally (PO) per the discretion of the treating investigator. Doses are administered every 8 hours. When given IV, TXA 1.0 gram will be administered. When given PO, TXA 1.3 grams will be administered	IV Normal Saline or PO placebo pills administered after meeting inclusion/exclusion criteria Placebo: Doses will be given intravenous (IV) or orally (PO) per the discretion of the treating investigator. Doses are administered every 8 hours. When given IV, Normal Saline will be administered. When given PO, placebo pills will be administered
Period Title: Overall Study
STARTED	165	165
COMPLETED	145	144
NOT COMPLETED	20	21

Baseline Characteristics

Arm/Group Title	Tranexamic Acid (TXA)	Placebo	Total
Arm/Group Description	IV or PO administered after meeting inclusion/exclusion criteria Tranexamic Acid: Doses will be given intravenous (IV) or orally (PO) per the discretion of the treating investigator. Doses are administered every 8 hours. When given IV, TXA 1.0 gram will be administered. When given PO, TXA 1.3 grams will be administered	IV Normal Saline or PO placebo pills administered after meeting inclusion/exclusion criteria Placebo: Doses will be given intravenous (IV) or orally (PO) per the discretion of the treating investigator. Doses are administered every 8 hours. When given IV, Normal Saline will be administered. When given PO, placebo pills will be administered	Total of all reporting groups
Overall Participants	165	165	330
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.1 (13.0)	54.3 (13.2)	54.2 (13.1)
Sex: Female, Male (Count of Participants)
Female	73 44.2%	65 39.4%	138 41.8%
Male	92 55.8%	100 60.6%	192 58.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	2 1.2%	4 2.4%	6 1.8%
Asian	3 1.8%	9 5.5%	12 3.6%
Native Hawaiian or Other Pacific Islander	2 1.2%	3 1.8%	5 1.5%
Black or African American	11 6.7%	12 7.3%	23 7%
White	141 85.5%	129 78.2%	270 81.8%
More than one race	1 0.6%	5 3%	6 1.8%
Unknown or Not Reported	5 3%	3 1.8%	8 2.4%

Outcome Measures

1. Primary Outcome

Title	Bleeding Within 30 Days
Description	Proportion of patients with bleeding of WHO grade 2 or above, over the study period of 30 days after activation of study drug.
Time Frame	30 days after activation of study drug

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tranexamic Acid (TXA)	Placebo
Arm/Group Description	IV or PO administered after meeting inclusion/exclusion criteria Tranexamic Acid: Doses will be given intravenous (IV) or orally (PO) per the discretion of the treating investigator. Doses are administered every 8 hours. When given IV, TXA 1.0 gram will be administered. When given PO, TXA 1.3 grams will be administered	IV Normal Saline or PO placebo pills administered after meeting inclusion/exclusion criteria Placebo: Doses will be given intravenous (IV) or orally (PO) per the discretion of the treating investigator. Doses are administered every 8 hours. When given IV, Normal Saline will be administered. When given PO, placebo pills will be administered
Measure Participants	145	144
Count of Participants [Participants]	73 44.2%	78 47.3%

2. Secondary Outcome

Title	Number of Platelet Transfusions
Description	Number of platelet transfusions per patient during the first 30 days post prescription activation of study drug
Time Frame	30 days after activation of study drug

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tranexamic Acid (TXA)	Placebo
Arm/Group Description	IV or PO administered after meeting inclusion/exclusion criteria Tranexamic Acid: Doses will be given intravenous (IV) or orally (PO) per the discretion of the treating investigator. Doses are administered every 8 hours. When given IV, TXA 1.0 gram will be administered. When given PO, TXA 1.3 grams will be administered	IV Normal Saline or PO placebo pills administered after meeting inclusion/exclusion criteria Placebo: Doses will be given intravenous (IV) or orally (PO) per the discretion of the treating investigator. Doses are administered every 8 hours. When given IV, Normal Saline will be administered. When given PO, placebo pills will be administered
Measure Participants	165	165
Mean (Standard Deviation) [platelet transfusions]	7.7 (8.7)	7.6 (10.1)

3. Secondary Outcome

Title	Number of Days Alive and Without WHO Grade 2 Bleeding
Description	Number of days alive and without WHO grade 2 bleeding or greater during the first 30 days post activation of study drug
Time Frame	during the first 30 days post activation of study drug

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tranexamic Acid (TXA)	Placebo
Arm/Group Description	IV or PO administered after meeting inclusion/exclusion criteria Tranexamic Acid: Doses will be given intravenous (IV) or orally (PO) per the discretion of the treating investigator. Doses are administered every 8 hours. When given IV, TXA 1.0 gram will be administered. When given PO, TXA 1.3 grams will be administered	IV Normal Saline or PO placebo pills administered after meeting inclusion/exclusion criteria Placebo: Doses will be given intravenous (IV) or orally (PO) per the discretion of the treating investigator. Doses are administered every 8 hours. When given IV, Normal Saline will be administered. When given PO, placebo pills will be administered
Measure Participants	136	132
Mean (Standard Deviation) [days]	28.1 (3.7)	27.7 (4.7)

Adverse Events

Time Frame	120 days after activation
Arm/Group Title	Tranexamic Acid (TXA)		Placebo
Arm/Group Description	IV or PO administered after meeting inclusion/exclusion criteria Tranexamic Acid: Doses will be given intravenous (IV) or orally (PO) per the discretion of the treating investigator. Doses are administered every 8 hours. When given IV, TXA 1.0 gram will be administered. When given PO, TXA 1.3 grams will be administered		IV Normal Saline or PO placebo pills administered after meeting inclusion/exclusion criteria Placebo: Doses will be given intravenous (IV) or orally (PO) per the discretion of the treating investigator. Doses are administered every 8 hours. When given IV, Normal Saline will be administered. When given PO, placebo pills will be administered
All Cause Mortality
	Tranexamic Acid (TXA)		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	19/163 (11.7%)		19/163 (11.7%)
Serious Adverse Events
	Tranexamic Acid (TXA)		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	123/163 (75.5%)		110/163 (67.5%)
Blood and lymphatic system disorders
Febrile neutropenia	40/163 (24.5%)		36/163 (22.1%)
Other blood/lymph disorder	2/163 (1.2%)		0/163 (0%)
Anemia	0/163 (0%)		1/163 (0.6%)
Spleen disorder	0/163 (0%)		1/163 (0.6%)
Hemolysis	1/163 (0.6%)		0/163 (0%)
Cardiac disorders
Sinus tachycardia	10/163 (6.1%)		9/163 (5.5%)
Other cardiac	3/163 (1.8%)		4/163 (2.5%)
Atrial fibrillation	2/163 (1.2%)		3/163 (1.8%)
Atrial flutter	2/163 (1.2%)		1/163 (0.6%)
Cardiac arrest	1/163 (0.6%)		1/163 (0.6%)
Ventricular arrhythmia	1/163 (0.6%)		1/163 (0.6%)
Pericardial effusion	0/163 (0%)		2/163 (1.2%)
Heart failure	1/163 (0.6%)		1/163 (0.6%)
Palpitations	0/163 (0%)		2/163 (1.2%)
Myocardial infarction	0/163 (0%)		1/163 (0.6%)
RV dysfunction	1/163 (0.6%)		0/163 (0%)
Chest pain - cardiac	0/163 (0%)		1/163 (0.6%)
Sinus bradycardia	1/163 (0.6%)		0/163 (0%)
Mitral valve disease	1/163 (0.6%)		0/163 (0%)
Tricuspid valve disease	1/163 (0.6%)		0/163 (0%)
Congenital, familial and genetic disorders
Other congenital	1/163 (0.6%)		0/163 (0%)
Ear and labyrinth disorders
Tinnitus	0/163 (0%)		3/163 (1.8%)
Ear pain	2/163 (1.2%)		0/163 (0%)
Other	0/163 (0%)		1/163 (0.6%)
Eye disorders
Blurred vision	1/163 (0.6%)		3/163 (1.8%)
Other eye disorder	2/163 (1.2%)		2/163 (1.2%)
Eye pain	0/163 (0%)		1/163 (0.6%)
Gastrointestinal disorders
Nausea	27/163 (16.6%)		16/163 (9.8%)
Diarrhea	8/163 (4.9%)		11/163 (6.7%)
Abdominal pain	8/163 (4.9%)		11/163 (6.7%)
Vomiting	9/163 (5.5%)		7/163 (4.3%)
Constipation	10/163 (6.1%)		4/163 (2.5%)
Other gastrointestinal	4/163 (2.5%)		6/163 (3.7%)
Mucositis oral	4/163 (2.5%)		3/163 (1.8%)
Dyspepsia	2/163 (1.2%)		5/163 (3.1%)
Dysphagia	2/163 (1.2%)		3/163 (1.8%)
Esophageal pain	2/163 (1.2%)		3/163 (1.8%)
Rectal pain	4/163 (2.5%)		0/163 (0%)
Dry mouth	3/163 (1.8%)		1/163 (0.6%)
Ascites	1/163 (0.6%)		2/163 (1.2%)
Bloating	1/163 (0.6%)		1/163 (0.6%)
Hemorrhoids	2/163 (1.2%)		0/163 (0%)
Rectal ulcer	0/163 (0%)		1/163 (0.6%)
Small intestinal obstruction	1/163 (0.6%)		0/163 (0%)
Typhlitis	1/163 (0.6%)		0/163 (0%)
Rectal fistula	0/163 (0%)		1/163 (0.6%)
Rectal hemorrhage	1/163 (0.6%)		0/163 (0%)
Gastroesoph reflux disease	1/163 (0.6%)		0/163 (0%)
Abdominal distension	0/163 (0%)		1/163 (0.6%)
Oral pain	0/163 (0%)		1/163 (0.6%)
General disorders
Fatigue	17/163 (10.4%)		15/163 (9.2%)
Fever	12/163 (7.4%)		12/163 (7.4%)
Edema limbs	7/163 (4.3%)		13/163 (8%)
Infusion related reaction	3/163 (1.8%)		5/163 (3.1%)
Other general disorder	3/163 (1.8%)		2/163 (1.2%)
Pain	1/163 (0.6%)		3/163 (1.8%)
Chills	0/163 (0%)		4/163 (2.5%)
Non-cardiac chest pain	0/163 (0%)		4/163 (2.5%)
Multi-organ failure	0/163 (0%)		2/163 (1.2%)
Edema face	1/163 (0.6%)		1/163 (0.6%)
Malaise	1/163 (0.6%)		0/163 (0%)
Neck edema	1/163 (0.6%)		0/163 (0%)
Facial pain	1/163 (0.6%)		0/163 (0%)
Hepatobiliary disorders
Other hepatobiliary	2/163 (1.2%)		2/163 (1.2%)
Hepatic failure	0/163 (0%)		2/163 (1.2%)
Cholecystitis	0/163 (0%)		1/163 (0.6%)
Immune system disorders
Other immune disorder	18/163 (11%)		12/163 (7.4%)
Allergic reaction	1/163 (0.6%)		0/163 (0%)
Infections and infestations
Other infection	19/163 (11.7%)		22/163 (13.5%)
Sepsis	5/163 (3.1%)		10/163 (6.1%)
Lung infection	2/163 (1.2%)		8/163 (4.9%)
Sinusitis	3/163 (1.8%)		5/163 (3.1%)
Upper respiratory infection	4/163 (2.5%)		3/163 (1.8%)
Urinary tract infection	4/163 (2.5%)		1/163 (0.6%)
Skin infection	2/163 (1.2%)		3/163 (1.8%)
Abdominal infection	0/163 (0%)		1/163 (0.6%)
Papulopustular rash	0/163 (0%)		1/163 (0.6%)
Meningitis	0/163 (0%)		1/163 (0.6%)
Catheter related infection	1/163 (0.6%)		0/163 (0%)
Injury, poisoning and procedural complications
Fall	4/163 (2.5%)		2/163 (1.2%)
Other injury	3/163 (1.8%)		3/163 (1.8%)
Bruising	3/163 (1.8%)		0/163 (0%)
Gastric anastomotic leak	0/163 (0%)		1/163 (0.6%)
Investigations
ALT increased	1/163 (0.6%)		4/163 (2.5%)
Creatinine increased	3/163 (1.8%)		2/163 (1.2%)
Weight gain	3/163 (1.8%)		2/163 (1.2%)
AST increased	1/163 (0.6%)		3/163 (1.8%)
Blood bilirubin increased	1/163 (0.6%)		2/163 (1.2%)
Other investigation abnormal	1/163 (0.6%)		2/163 (1.2%)
Urine output decreased	1/163 (0.6%)		2/163 (1.2%)
Weight loss	0/163 (0%)		2/163 (1.2%)
Alk phos increased	0/163 (0%)		1/163 (0.6%)
Metabolism and nutrition disorders
Anorexia	11/163 (6.7%)		5/163 (3.1%)
Other metabolism disorder	4/163 (2.5%)		2/163 (1.2%)
Hyperglycemia	4/163 (2.5%)		1/163 (0.6%)
Hypomagnesemia	3/163 (1.8%)		2/163 (1.2%)
Acidosis	1/163 (0.6%)		3/163 (1.8%)
Hyperkalemia	2/163 (1.2%)		1/163 (0.6%)
Hypokalemia	1/163 (0.6%)		2/163 (1.2%)
Dehydration	2/163 (1.2%)		0/163 (0%)
Hypernatremia	0/163 (0%)		2/163 (1.2%)
Hypoglycemia	2/163 (1.2%)		0/163 (0%)
Hyponatremia	1/163 (0.6%)		1/163 (0.6%)
Hyperuricemia	0/163 (0%)		1/163 (0.6%)
Iron overload	0/163 (0%)		1/163 (0.6%)
Hypercalcemia	0/163 (0%)		1/163 (0.6%)
Musculoskeletal and connective tissue disorders
Back pain	7/163 (4.3%)		8/163 (4.9%)
Pain in extremity	7/163 (4.3%)		5/163 (3.1%)
Arthralgia	5/163 (3.1%)		3/163 (1.8%)
Generalized muscle weakness	2/163 (1.2%)		4/163 (2.5%)
Neck pain	1/163 (0.6%)		2/163 (1.2%)
Other musculoskeletal disorder	0/163 (0%)		2/163 (1.2%)
Bone pain	0/163 (0%)		2/163 (1.2%)
Myalgia	2/163 (1.2%)		0/163 (0%)
Joint ROM decreased	0/163 (0%)		1/163 (0.6%)
Muscle weakness lower limb	1/163 (0.6%)		0/163 (0%)
Arthritis	1/163 (0.6%)		0/163 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Other neoplasm	0/163 (0%)		2/163 (1.2%)
Nervous system disorders
Headache	16/163 (9.8%)		10/163 (6.1%)
Dizziness	9/163 (5.5%)		5/163 (3.1%)
Other nervous sys disorder	3/163 (1.8%)		5/163 (3.1%)
Paresthesia	4/163 (2.5%)		2/163 (1.2%)
Syncope	3/163 (1.8%)		1/163 (0.6%)
Peripheral sensory neuropathy	3/163 (1.8%)		1/163 (0.6%)
Intracranial hemorrhage	1/163 (0.6%)		2/163 (1.2%)
Encephalopathy	0/163 (0%)		3/163 (1.8%)
Seizure	1/163 (0.6%)		1/163 (0.6%)
Ataxia	1/163 (0.6%)		1/163 (0.6%)
Dysgeusia	2/163 (1.2%)		0/163 (0%)
Tremor	1/163 (0.6%)		1/163 (0.6%)
Akathisia	0/163 (0%)		1/163 (0.6%)
Ischemia cerebrovascular	1/163 (0.6%)		0/163 (0%)
Transient ischemic attacks	1/163 (0.6%)		0/163 (0%)
Stroke	1/163 (0.6%)		0/163 (0%)
Somnolence	1/163 (0.6%)		0/163 (0%)
Dysphasia	0/163 (0%)		1/163 (0.6%)
Dysesthesia	1/163 (0.6%)		0/163 (0%)
Memory impairment	0/163 (0%)		1/163 (0.6%)
Lethargy	0/163 (0%)		1/163 (0.6%)
Vasovagal reaction	0/163 (0%)		1/163 (0.6%)
Psychiatric disorders
Insomnia	11/163 (6.7%)		7/163 (4.3%)
Other psychiatric disorder	4/163 (2.5%)		2/163 (1.2%)
Anxiety	2/163 (1.2%)		3/163 (1.8%)
Depression	3/163 (1.8%)		1/163 (0.6%)
Delirium	1/163 (0.6%)		2/163 (1.2%)
Confusion	0/163 (0%)		3/163 (1.8%)
Restlessness	1/163 (0.6%)		0/163 (0%)
Renal and urinary disorders
Acute kidney injury	7/163 (4.3%)		6/163 (3.7%)
Other renal disorder	5/163 (3.1%)		2/163 (1.2%)
Urinary frequency	2/163 (1.2%)		2/163 (1.2%)
Hematuria	1/163 (0.6%)		1/163 (0.6%)
Renal calculi	0/163 (0%)		2/163 (1.2%)
Urinary incontinence	0/163 (0%)		2/163 (1.2%)
Urinary retention	1/163 (0.6%)		0/163 (0%)
Urinary urgency	0/163 (0%)		1/163 (0.6%)
Reproductive system and breast disorders
Other reproductive sys disorder	3/163 (1.8%)		3/163 (1.8%)
Testicular pain	1/163 (0.6%)		0/163 (0%)
Menorrhagia	0/163 (0%)		1/163 (0.6%)
Erectile dysfunction	0/163 (0%)		1/163 (0.6%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	10/163 (6.1%)		10/163 (6.1%)
Other respiratory disorder	8/163 (4.9%)		11/163 (6.7%)
Hypoxia	10/163 (6.1%)		7/163 (4.3%)
Respiratory failure	5/163 (3.1%)		7/163 (4.3%)
Cough	3/163 (1.8%)		7/163 (4.3%)
Allergic rhinitis	3/163 (1.8%)		7/163 (4.3%)
Pulmonary edema	3/163 (1.8%)		4/163 (2.5%)
Pleural effusion	1/163 (0.6%)		5/163 (3.1%)
Pharyngeal mucositis	3/163 (1.8%)		3/163 (1.8%)
Bronchopulmonary hemorrhage	2/163 (1.2%)		2/163 (1.2%)
Epistaxis	1/163 (0.6%)		3/163 (1.8%)
Nasal congestion	0/163 (0%)		3/163 (1.8%)
Sore throat	2/163 (1.2%)		1/163 (0.6%)
Atelectasis	1/163 (0.6%)		1/163 (0.6%)
Pulmonary hypertension	1/163 (0.6%)		1/163 (0.6%)
Apnea	1/163 (0.6%)		0/163 (0%)
Pharyngolaryngeal pain	1/163 (0.6%)		0/163 (0%)
Productive cough	0/163 (0%)		1/163 (0.6%)
Skin and subcutaneous tissue disorders
Rash maculo-papular	5/163 (3.1%)		12/163 (7.4%)
Other skin disorder	5/163 (3.1%)		7/163 (4.3%)
Pruritus	4/163 (2.5%)		4/163 (2.5%)
Dry skin	4/163 (2.5%)		3/163 (1.8%)
Skin ulceration	4/163 (2.5%)		1/163 (0.6%)
Hyperhidrosis	2/163 (1.2%)		3/163 (1.8%)
Purpura	1/163 (0.6%)		1/163 (0.6%)
Skin hyperpigmentation	0/163 (0%)		2/163 (1.2%)
Skin induration	0/163 (0%)		1/163 (0.6%)
Bullous dermatitis	1/163 (0.6%)		0/163 (0%)
Pain of skin	0/163 (0%)		1/163 (0.6%)
Vascular disorders
Hypotension	13/163 (8%)		11/163 (6.7%)
Hypertension	6/163 (3.7%)		7/163 (4.3%)
Thromboembolic event	3/163 (1.8%)		4/163 (2.5%)
Flushing	1/163 (0.6%)		0/163 (0%)
Other (Not Including Serious) Adverse Events
	Tranexamic Acid (TXA)		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	161/163 (98.8%)		161/163 (98.8%)
Blood and lymphatic system disorders
Febrile neutropenia	81/163 (49.7%)		75/163 (46%)
Cardiac disorders
Sinus tachycardia	70/163 (42.9%)		65/163 (39.9%)
Sinus bradycardia	14/163 (8.6%)		8/163 (4.9%)
Other cardiac	10/163 (6.1%)		6/163 (3.7%)
Ear and labyrinth disorders
Other	9/163 (5.5%)		4/163 (2.5%)
Eye disorders
Blurred vision	18/163 (11%)		12/163 (7.4%)
Other eye disorder	9/163 (5.5%)		18/163 (11%)
Gastrointestinal disorders
Diarrhea	114/163 (69.9%)		112/163 (68.7%)
Nausea	95/163 (58.3%)		91/163 (55.8%)
Abdominal pain	68/163 (41.7%)		55/163 (33.7%)
Mucositis oral	58/163 (35.6%)		63/163 (38.7%)
Vomiting	65/163 (39.9%)		56/163 (34.4%)
Constipation	43/163 (26.4%)		52/163 (31.9%)
Other gastrointestinal	36/163 (22.1%)		42/163 (25.8%)
Dry mouth	20/163 (12.3%)		25/163 (15.3%)
Dyspepsia	26/163 (16%)		17/163 (10.4%)
Oral pain	15/163 (9.2%)		15/163 (9.2%)
Gastroesoph reflux disease	13/163 (8%)		14/163 (8.6%)
Bloating	14/163 (8.6%)		11/163 (6.7%)
Rectal pain	12/163 (7.4%)		12/163 (7.4%)
Hemorrhoids	16/163 (9.8%)		7/163 (4.3%)
Fecal incontinence	6/163 (3.7%)		11/163 (6.7%)
Abdominal distension	9/163 (5.5%)		7/163 (4.3%)
General disorders
Fatigue	100/163 (61.3%)		102/163 (62.6%)
Edema limbs	65/163 (39.9%)		64/163 (39.3%)
Chills	28/163 (17.2%)		27/163 (16.6%)
Infusion related reaction	26/163 (16%)		29/163 (17.8%)
Fever	25/163 (15.3%)		28/163 (17.2%)
Other general disorder	26/163 (16%)		24/163 (14.7%)
Pain	23/163 (14.1%)		15/163 (9.2%)
Injection site reaction	15/163 (9.2%)		17/163 (10.4%)
Non-cardiac chest pain	16/163 (9.8%)		9/163 (5.5%)
Localized edema	11/163 (6.7%)		12/163 (7.4%)
Edema face	11/163 (6.7%)		11/163 (6.7%)
Hepatobiliary disorders
Other hepatobiliary	11/163 (6.7%)		8/163 (4.9%)
Immune system disorders
Other immune disorder	21/163 (12.9%)		14/163 (8.6%)
Infections and infestations
Other infection	52/163 (31.9%)		52/163 (31.9%)
Skin infection	14/163 (8.6%)		22/163 (13.5%)
Sinusitis	13/163 (8%)		15/163 (9.2%)
Lung infection	14/163 (8.6%)		6/163 (3.7%)
Injury, poisoning and procedural complications
Other injury	9/163 (5.5%)		13/163 (8%)
Investigations
ALT increased	27/163 (16.6%)		19/163 (11.7%)
AST increased	22/163 (13.5%)		16/163 (9.8%)
Weight gain	10/163 (6.1%)		12/163 (7.4%)
Blood bilirubin increased	15/163 (9.2%)		7/163 (4.3%)
Metabolism and nutrition disorders
Anorexia	69/163 (42.3%)		65/163 (39.9%)
Hyperglycemia	30/163 (18.4%)		23/163 (14.1%)
Other metabolism disorder	25/163 (15.3%)		22/163 (13.5%)
Hypokalemia	24/163 (14.7%)		19/163 (11.7%)
Hypomagnesemia	15/163 (9.2%)		18/163 (11%)
Hyponatremia	13/163 (8%)		11/163 (6.7%)
Hypophosphatemia	9/163 (5.5%)		6/163 (3.7%)
Musculoskeletal and connective tissue disorders
Arthralgia	42/163 (25.8%)		44/163 (27%)
Generalized muscle weakness	32/163 (19.6%)		35/163 (21.5%)
Back pain	36/163 (22.1%)		28/163 (17.2%)
Pain in extremity	32/163 (19.6%)		30/163 (18.4%)
Neck pain	12/163 (7.4%)		8/163 (4.9%)
Myalgia	6/163 (3.7%)		11/163 (6.7%)
Bone pain	8/163 (4.9%)		9/163 (5.5%)
Other musculoskeletal disorder	4/163 (2.5%)		10/163 (6.1%)
Nervous system disorders
Headache	66/163 (40.5%)		67/163 (41.1%)
Dizziness	38/163 (23.3%)		38/163 (23.3%)
Dysgeusia	34/163 (20.9%)		30/163 (18.4%)
Tremor	16/163 (9.8%)		19/163 (11.7%)
Peripheral sensory neuropathy	14/163 (8.6%)		14/163 (8.6%)
Paresthesia	9/163 (5.5%)		15/163 (9.2%)
Psychiatric disorders
Insomnia	37/163 (22.7%)		49/163 (30.1%)
Anxiety	30/163 (18.4%)		33/163 (20.2%)
Confusion	13/163 (8%)		11/163 (6.7%)
Depression	10/163 (6.1%)		11/163 (6.7%)
Other psychiatric disorder	9/163 (5.5%)		8/163 (4.9%)
Renal and urinary disorders
Other renal disorder	27/163 (16.6%)		26/163 (16%)
Urinary frequency	19/163 (11.7%)		13/163 (8%)
Acute kidney injury	8/163 (4.9%)		17/163 (10.4%)
Urinary urgency	10/163 (6.1%)		11/163 (6.7%)
Urinary incontinence	9/163 (5.5%)		8/163 (4.9%)
Urinary retention	9/163 (5.5%)		5/163 (3.1%)
Reproductive system and breast disorders
Other reproductive sys disorder	9/163 (5.5%)		11/163 (6.7%)
Respiratory, thoracic and mediastinal disorders
Cough	38/163 (23.3%)		53/163 (32.5%)
Dyspnea	40/163 (24.5%)		41/163 (25.2%)
Other respiratory disorder	33/163 (20.2%)		33/163 (20.2%)
Allergic rhinitis	32/163 (19.6%)		33/163 (20.2%)
Pharyngeal mucositis	24/163 (14.7%)		31/163 (19%)
Productive cough	26/163 (16%)		21/163 (12.9%)
Sore throat	20/163 (12.3%)		20/163 (12.3%)
Hypoxia	23/163 (14.1%)		17/163 (10.4%)
Pleural effusion	17/163 (10.4%)		16/163 (9.8%)
Pulmonary edema	15/163 (9.2%)		16/163 (9.8%)
Pharyngolaryngeal pain	9/163 (5.5%)		18/163 (11%)
Nasal congestion	12/163 (7.4%)		11/163 (6.7%)
Wheezing	14/163 (8.6%)		9/163 (5.5%)
Atelectasis	9/163 (5.5%)		8/163 (4.9%)
Skin and subcutaneous tissue disorders
Rash maculo-papular	71/163 (43.6%)		62/163 (38%)
Other skin disorder	40/163 (24.5%)		53/163 (32.5%)
Pruritus	41/163 (25.2%)		48/163 (29.4%)
Dry skin	20/163 (12.3%)		31/163 (19%)
Hyperhidrosis	13/163 (8%)		16/163 (9.8%)
Skin ulceration	17/163 (10.4%)		10/163 (6.1%)
Vascular disorders
Hypotension	53/163 (32.5%)		56/163 (34.4%)
Hypertension	50/163 (30.7%)		56/163 (34.4%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.