Trial Outcomes & Findings for Catheter-Related Early Thromboprophylaxis With Enoxaparin (CRETE) Trial (NCT NCT03003390)

Last Updated: 2020-07-13

Results Overview

Thrombus in the central vein where the CVC was inserted that is clinically suspected then confirmed radiologically, an incidental radiologic finding, or diagnosed with the study-related active surveillance ultrasound

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

51 participants

Primary outcome timeframe

Up to removal of CVC, an average of 6 days

Results posted on

2020-07-13

Participant Flow

One participant in the enoxaparin group was enrolled during a single arm phase and not included in the analysis.

Participant milestones

Participant milestones
Measure	Prophylaxis With Enoxaparin A clinical nurse will administer enoxaparin subcutaneously \<24 hours after insertion of the central venous catheter and then give enoxaparin subcutaneously every 12 hours until the removal of the catheter. Enoxaparin: The clinical nurse will give enoxaparin subcutaneously every 12 hours at the currently used starting dose of 0.75 mg/kg for children ≤2 months old or 0.5 mg/kg (maximum of 40 mg) for older children. The 1st dose will be given \<24 hours after insertion of the catheter. Doses will be adjusted to target an anti-Xa level of 0.2-0.5 IU/mL.	Control Arm Participants randomized to the control arm will receive no 'placebo' intervention.
Overall Study STARTED	27	24
Overall Study COMPLETED	23	24
Overall Study NOT COMPLETED	4	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Prophylaxis With Enoxaparin A clinical nurse will administer enoxaparin subcutaneously \<24 hours after insertion of the central venous catheter and then give enoxaparin subcutaneously every 12 hours until the removal of the catheter. Enoxaparin: The clinical nurse will give enoxaparin subcutaneously every 12 hours at the currently used starting dose of 0.75 mg/kg for children ≤2 months old or 0.5 mg/kg (maximum of 40 mg) for older children. The 1st dose will be given \<24 hours after insertion of the catheter. Doses will be adjusted to target an anti-Xa level of 0.2-0.5 IU/mL.	Control Arm Participants randomized to the control arm will receive no 'placebo' intervention.
Overall Study Physician Decision	2	0
Overall Study Parent refused intervention	2	0

Baseline Characteristics

Catheter-Related Early Thromboprophylaxis With Enoxaparin (CRETE) Trial

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Prophylaxis With Enoxaparin n=27 Participants A clinical nurse will administer enoxaparin subcutaneously \<24 hours after insertion of the central venous catheter and then give enoxaparin subcutaneously every 12 hours until the removal of the catheter. Enoxaparin: The clinical nurse will give enoxaparin subcutaneously every 12 hours at the currently used starting dose of 0.75 mg/kg for children ≤2 months old or 0.5 mg/kg (maximum of 40 mg) for older children. The 1st dose will be given \<24 hours after insertion of the catheter. Doses will be adjusted to target an anti-Xa level of 0.2-0.5 IU/mL.	Control Arm n=24 Participants Participants randomized to the control arm will receive no 'placebo' intervention.	Total n=51 Participants Total of all reporting groups
Age, Customized <1 year old	12 Participants n=5 Participants	12 Participants n=7 Participants	24 Participants n=5 Participants
Age, Customized 1-13 years old	13 Participants n=5 Participants	10 Participants n=7 Participants	23 Participants n=5 Participants
Age, Customized >13 years old	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Sex: Female, Male Female	16 Participants n=5 Participants	12 Participants n=7 Participants	28 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	12 Participants n=7 Participants	23 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	22 Participants n=5 Participants	19 Participants n=7 Participants	41 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	6 Participants n=5 Participants	7 Participants n=7 Participants	13 Participants n=5 Participants
Race (NIH/OMB) White	20 Participants n=5 Participants	17 Participants n=7 Participants	37 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Size of Central Venous Catheter (CVC) 3 French (F)	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Size of Central Venous Catheter (CVC) 4 F	13 Participants n=5 Participants	11 Participants n=7 Participants	24 Participants n=5 Participants
Size of Central Venous Catheter (CVC) 5 F	10 Participants n=5 Participants	10 Participants n=7 Participants	20 Participants n=5 Participants
Size of Central Venous Catheter (CVC) 7 F	4 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants
Number of Lumens of CVC 1	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Number of Lumens of CVC 2	15 Participants n=5 Participants	12 Participants n=7 Participants	27 Participants n=5 Participants
Number of Lumens of CVC 3	12 Participants n=5 Participants	10 Participants n=7 Participants	22 Participants n=5 Participants
Site of Insertion of CVC Left Femoral	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Site of Insertion of CVC Right Internal Jugular	15 Participants n=5 Participants	13 Participants n=7 Participants	28 Participants n=5 Participants
Site of Insertion of CVC Right Femoral	8 Participants n=5 Participants	7 Participants n=7 Participants	15 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to removal of CVC, an average of 6 days

Outcome measures

Outcome measures
Measure	Prophylaxis With Enoxaparin n=23 Participants A clinical nurse will administer enoxaparin subcutaneously \<24 hours after insertion of the central venous catheter and then give enoxaparin subcutaneously every 12 hours until the removal of the catheter. Enoxaparin: The clinical nurse will give enoxaparin subcutaneously every 12 hours at the currently used starting dose of 0.75 mg/kg for children ≤2 months old or 0.5 mg/kg (maximum of 40 mg) for older children. The 1st dose will be given \<24 hours after insertion of the catheter. Doses will be adjusted to target an anti-Xa level of 0.2-0.5 IU/mL.	Control Arm n=24 Participants Participants randomized to the control arm will receive no 'placebo' intervention.
Number of Participants With Central Venous Catheter (CVC)- Associated Deep Vein Thrombosis (DVT)	7 Participants	13 Participants

PRIMARY outcome

Timeframe: Day of, day after and day 4 after insertion of the CVC

Population: The numbers analyzed on the day after CVC insertion and four days after CVC insertion differ from the overall number of participants. Participants were excluded if the CVC was removed or if blood was not drawn.

An established measure of coagulation status and is the best method to measure thrombin generation. It directly measures the amount of thrombin generation over time capturing the effects of natural (i.e., subject's coagulation status) and pharmacological (e.g., enoxaparin) pro- and anticoagulants. Endogenous thrombin potential is measured using thrombin generation assay.

Outcome measures

Outcome measures
Measure	Prophylaxis With Enoxaparin n=27 Participants A clinical nurse will administer enoxaparin subcutaneously \<24 hours after insertion of the central venous catheter and then give enoxaparin subcutaneously every 12 hours until the removal of the catheter. Enoxaparin: The clinical nurse will give enoxaparin subcutaneously every 12 hours at the currently used starting dose of 0.75 mg/kg for children ≤2 months old or 0.5 mg/kg (maximum of 40 mg) for older children. The 1st dose will be given \<24 hours after insertion of the catheter. Doses will be adjusted to target an anti-Xa level of 0.2-0.5 IU/mL.	Control Arm n=24 Participants Participants randomized to the control arm will receive no 'placebo' intervention.
Endogenous Thrombin Potential Day of CVC Insertion	919.7 Nanomolar-minute (nM.min) Interval 418.71 to 1150.77	1035.6 Nanomolar-minute (nM.min) Interval 800.22 to 1455.05
Endogenous Thrombin Potential Day After CVC Insertion	851.19 Nanomolar-minute (nM.min) Interval 627.31 to 995.98	896.58 Nanomolar-minute (nM.min) Interval 433.9 to 1331.03
Endogenous Thrombin Potential Day 4 After CVC Insertion	826.97 Nanomolar-minute (nM.min) Interval 0.0 to 1131.7	969.89 Nanomolar-minute (nM.min) Interval 605.35 to 1302.95

SECONDARY outcome

Timeframe: Up to removal of CVC, an average of 6 days

Thrombus in the deep vein of any extremity or PE that is clinically suspected then confirmed radiologically, an incidental radiologic finding, excluding DVT diagnosed with the study-related active surveillance ultrasound

Outcome measures

Outcome measures
Measure	Prophylaxis With Enoxaparin n=27 Participants A clinical nurse will administer enoxaparin subcutaneously \<24 hours after insertion of the central venous catheter and then give enoxaparin subcutaneously every 12 hours until the removal of the catheter. Enoxaparin: The clinical nurse will give enoxaparin subcutaneously every 12 hours at the currently used starting dose of 0.75 mg/kg for children ≤2 months old or 0.5 mg/kg (maximum of 40 mg) for older children. The 1st dose will be given \<24 hours after insertion of the catheter. Doses will be adjusted to target an anti-Xa level of 0.2-0.5 IU/mL.	Control Arm n=24 Participants Participants randomized to the control arm will receive no 'placebo' intervention.
Number With Other Thromboembolic Events	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Up to day of discharge from the pediatric intensive care unit, an average of 10 days

Duration of stay in the pediatric intensive care unit from the day of enrollment

Outcome measures

Outcome measures
Measure	Prophylaxis With Enoxaparin n=27 Participants A clinical nurse will administer enoxaparin subcutaneously \<24 hours after insertion of the central venous catheter and then give enoxaparin subcutaneously every 12 hours until the removal of the catheter. Enoxaparin: The clinical nurse will give enoxaparin subcutaneously every 12 hours at the currently used starting dose of 0.75 mg/kg for children ≤2 months old or 0.5 mg/kg (maximum of 40 mg) for older children. The 1st dose will be given \<24 hours after insertion of the catheter. Doses will be adjusted to target an anti-Xa level of 0.2-0.5 IU/mL.	Control Arm n=24 Participants Participants randomized to the control arm will receive no 'placebo' intervention.
Length of Stay in the Pediatric Intensive Care Unit in Days	12 days Interval 6.0 to 22.0	8 days Interval 4.0 to 16.0

SECONDARY outcome

Timeframe: Up to day of discharge from the hospital, an average of 18 days

Duration of stay in the hospital from the day of enrollment

Outcome measures

Outcome measures
Measure	Prophylaxis With Enoxaparin n=27 Participants A clinical nurse will administer enoxaparin subcutaneously \<24 hours after insertion of the central venous catheter and then give enoxaparin subcutaneously every 12 hours until the removal of the catheter. Enoxaparin: The clinical nurse will give enoxaparin subcutaneously every 12 hours at the currently used starting dose of 0.75 mg/kg for children ≤2 months old or 0.5 mg/kg (maximum of 40 mg) for older children. The 1st dose will be given \<24 hours after insertion of the catheter. Doses will be adjusted to target an anti-Xa level of 0.2-0.5 IU/mL.	Control Arm n=24 Participants Participants randomized to the control arm will receive no 'placebo' intervention.
Length of Stay in the Hospital	16 days Interval 6.0 to 35.0	16 days Interval 7.0 to 23.0

SECONDARY outcome

Timeframe: Up to 30 hours after the last enoxaparin dose

Bleeding that is fatal, associated with a decrease in hemoglobin by ≥2 g/dl in 24 hours, requires medical or surgical intervention to restore hemostasis, or is in the retroperitoneum, pulmonary, intracranial or central nervous system as defined by International Society of Thrombosis and Haemostasis

Outcome measures

Outcome measures
Measure	Prophylaxis With Enoxaparin n=27 Participants A clinical nurse will administer enoxaparin subcutaneously \<24 hours after insertion of the central venous catheter and then give enoxaparin subcutaneously every 12 hours until the removal of the catheter. Enoxaparin: The clinical nurse will give enoxaparin subcutaneously every 12 hours at the currently used starting dose of 0.75 mg/kg for children ≤2 months old or 0.5 mg/kg (maximum of 40 mg) for older children. The 1st dose will be given \<24 hours after insertion of the catheter. Doses will be adjusted to target an anti-Xa level of 0.2-0.5 IU/mL.	Control Arm n=24 Participants Participants randomized to the control arm will receive no 'placebo' intervention.
Number With Clinically Relevant Bleeding	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to removal of CVC, an average of 6 days

Population: None of the participants experienced this outcome; hence, a statistical analysis was not performed.

Heparin-induced thrombocytopenia that is diagnosed with a positive serotonin release assay

Outcome measures

Outcome measures
Measure	Prophylaxis With Enoxaparin n=27 Participants A clinical nurse will administer enoxaparin subcutaneously \<24 hours after insertion of the central venous catheter and then give enoxaparin subcutaneously every 12 hours until the removal of the catheter. Enoxaparin: The clinical nurse will give enoxaparin subcutaneously every 12 hours at the currently used starting dose of 0.75 mg/kg for children ≤2 months old or 0.5 mg/kg (maximum of 40 mg) for older children. The 1st dose will be given \<24 hours after insertion of the catheter. Doses will be adjusted to target an anti-Xa level of 0.2-0.5 IU/mL.	Control Arm n=24 Participants Participants randomized to the control arm will receive no 'placebo' intervention.
Number With Laboratory Confirmed Heparin-induced Thrombocytopenia	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to day of discharge from the hospital, average of 18 days

In-hospital mortality during the subject's admission

Outcome measures

Outcome measures
Measure	Prophylaxis With Enoxaparin n=27 Participants A clinical nurse will administer enoxaparin subcutaneously \<24 hours after insertion of the central venous catheter and then give enoxaparin subcutaneously every 12 hours until the removal of the catheter. Enoxaparin: The clinical nurse will give enoxaparin subcutaneously every 12 hours at the currently used starting dose of 0.75 mg/kg for children ≤2 months old or 0.5 mg/kg (maximum of 40 mg) for older children. The 1st dose will be given \<24 hours after insertion of the catheter. Doses will be adjusted to target an anti-Xa level of 0.2-0.5 IU/mL.	Control Arm n=24 Participants Participants randomized to the control arm will receive no 'placebo' intervention.
Number of Mortality	5 Participants	2 Participants

SECONDARY outcome

Timeframe: Up to 24 hours after insertion of CVC

Number of eligible children enrolled in the study.

Outcome measures

Outcome measures
Measure	Prophylaxis With Enoxaparin n=164 Participants A clinical nurse will administer enoxaparin subcutaneously \<24 hours after insertion of the central venous catheter and then give enoxaparin subcutaneously every 12 hours until the removal of the catheter. Enoxaparin: The clinical nurse will give enoxaparin subcutaneously every 12 hours at the currently used starting dose of 0.75 mg/kg for children ≤2 months old or 0.5 mg/kg (maximum of 40 mg) for older children. The 1st dose will be given \<24 hours after insertion of the catheter. Doses will be adjusted to target an anti-Xa level of 0.2-0.5 IU/mL.	Control Arm Participants randomized to the control arm will receive no 'placebo' intervention.
Number of Enrolled Eligible Children	51 Participants	—

SECONDARY outcome

Timeframe: Up to 48 hours after insertion of CVC

Time to first dose of enoxaparin

Outcome measures

Outcome measures
Measure	Prophylaxis With Enoxaparin n=27 Participants A clinical nurse will administer enoxaparin subcutaneously \<24 hours after insertion of the central venous catheter and then give enoxaparin subcutaneously every 12 hours until the removal of the catheter. Enoxaparin: The clinical nurse will give enoxaparin subcutaneously every 12 hours at the currently used starting dose of 0.75 mg/kg for children ≤2 months old or 0.5 mg/kg (maximum of 40 mg) for older children. The 1st dose will be given \<24 hours after insertion of the catheter. Doses will be adjusted to target an anti-Xa level of 0.2-0.5 IU/mL.	Control Arm Participants randomized to the control arm will receive no 'placebo' intervention.
Time to 1st Dose of Enoxaparin	21.1 hours from insertion of CVC Interval 14.7 to 23.5	—

SECONDARY outcome

Timeframe: Up to removal of CVC, an average of 6 days

Population: This outcome measure is only applicable to subjects in the enoxaparin arm because the control arm did not receive enoxaparin for which anti-Xa activity is used to titrate the dose. Only 12 participants in the enoxaparin arm achieved the target anti-Xa activity.

Time from insertion of the CVC to time that anti-Xa activity was within 0.2-0.5 IU/mL.

Outcome measures

Outcome measures
Measure	Prophylaxis With Enoxaparin n=12 Participants A clinical nurse will administer enoxaparin subcutaneously \<24 hours after insertion of the central venous catheter and then give enoxaparin subcutaneously every 12 hours until the removal of the catheter. Enoxaparin: The clinical nurse will give enoxaparin subcutaneously every 12 hours at the currently used starting dose of 0.75 mg/kg for children ≤2 months old or 0.5 mg/kg (maximum of 40 mg) for older children. The 1st dose will be given \<24 hours after insertion of the catheter. Doses will be adjusted to target an anti-Xa level of 0.2-0.5 IU/mL.	Control Arm Participants randomized to the control arm will receive no 'placebo' intervention.
Time to Target Anti-Xa Activity	70.4 hours from insertion of CVC Interval 47.4 to 92.2	—

SECONDARY outcome

Timeframe: Up to removal of CVC, an average of 6 days

Number of doses of enoxaparin that were not administered. This outcome measure was only applicable to the enoxaparin arm.

Outcome measures

Outcome measures
Measure	Prophylaxis With Enoxaparin n=272 Doses A clinical nurse will administer enoxaparin subcutaneously \<24 hours after insertion of the central venous catheter and then give enoxaparin subcutaneously every 12 hours until the removal of the catheter. Enoxaparin: The clinical nurse will give enoxaparin subcutaneously every 12 hours at the currently used starting dose of 0.75 mg/kg for children ≤2 months old or 0.5 mg/kg (maximum of 40 mg) for older children. The 1st dose will be given \<24 hours after insertion of the catheter. Doses will be adjusted to target an anti-Xa level of 0.2-0.5 IU/mL.	Control Arm Participants randomized to the control arm will receive no 'placebo' intervention.
Number of Missed Doses of Enoxaparin	8 Doses of enoxaparin	—

SECONDARY outcome

Timeframe: Up to 24 hours after removal of CVC

Number of children in whom ultrasound was not performed.

Outcome measures

Outcome measures
Measure	Prophylaxis With Enoxaparin n=51 Participants A clinical nurse will administer enoxaparin subcutaneously \<24 hours after insertion of the central venous catheter and then give enoxaparin subcutaneously every 12 hours until the removal of the catheter. Enoxaparin: The clinical nurse will give enoxaparin subcutaneously every 12 hours at the currently used starting dose of 0.75 mg/kg for children ≤2 months old or 0.5 mg/kg (maximum of 40 mg) for older children. The 1st dose will be given \<24 hours after insertion of the catheter. Doses will be adjusted to target an anti-Xa level of 0.2-0.5 IU/mL.	Control Arm Participants randomized to the control arm will receive no 'placebo' intervention.
Number of Children With Ultrasound	47 Participants	—

Adverse Events

Prophylaxis With Enoxaparin

Serious events: 2 serious events

Other events: 9 other events

Deaths: 5 deaths

Control Arm

Serious events: 0 serious events

Other events: 6 other events

Deaths: 2 deaths

Serious adverse events

Serious adverse events
Measure	Prophylaxis With Enoxaparin n=27 participants at risk A clinical nurse will administer enoxaparin subcutaneously \<24 hours after insertion of the central venous catheter and then give enoxaparin subcutaneously every 12 hours until the removal of the catheter. Enoxaparin: The clinical nurse will give enoxaparin subcutaneously every 12 hours at the currently used starting dose of 0.75 mg/kg for children ≤2 months old or 0.5 mg/kg (maximum of 40 mg) for older children. The 1st dose will be given \<24 hours after insertion of the catheter. Doses will be adjusted to target an anti-Xa level of 0.2-0.5 IU/mL.	Control Arm n=24 participants at risk Participants randomized to the control arm will receive no 'placebo' intervention.
Renal and urinary disorders acute kidney injury	3.7% 1/27 • From hospital admission to day of discharge for death, up to 60 days.	0.00% 0/24 • From hospital admission to day of discharge for death, up to 60 days.
Cardiac disorders Cardiac arrest	3.7% 1/27 • From hospital admission to day of discharge for death, up to 60 days.	0.00% 0/24 • From hospital admission to day of discharge for death, up to 60 days.

Other adverse events

Additional Information

Dr. E. Vincent S Faustino

Yale University

Phone: 203-785-4651

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Prophylaxis With Enoxaparin n=27 participants at risk A clinical nurse will administer enoxaparin subcutaneously \<24 hours after insertion of the central venous catheter and then give enoxaparin subcutaneously every 12 hours until the removal of the catheter. Enoxaparin: The clinical nurse will give enoxaparin subcutaneously every 12 hours at the currently used starting dose of 0.75 mg/kg for children ≤2 months old or 0.5 mg/kg (maximum of 40 mg) for older children. The 1st dose will be given \<24 hours after insertion of the catheter. Doses will be adjusted to target an anti-Xa level of 0.2-0.5 IU/mL.	Control Arm n=24 participants at risk Participants randomized to the control arm will receive no 'placebo' intervention.
Metabolism and nutrition disorders Acidosis	11.1% 3/27 • From hospital admission to day of discharge for death, up to 60 days.	4.2% 1/24 • From hospital admission to day of discharge for death, up to 60 days.
Blood and lymphatic system disorders Anemia	18.5% 5/27 • From hospital admission to day of discharge for death, up to 60 days.	12.5% 3/24 • From hospital admission to day of discharge for death, up to 60 days.
Respiratory, thoracic and mediastinal disorders Aspiration	3.7% 1/27 • From hospital admission to day of discharge for death, up to 60 days.	0.00% 0/24 • From hospital admission to day of discharge for death, up to 60 days.
General disorders Edema trunk	0.00% 0/27 • From hospital admission to day of discharge for death, up to 60 days.	4.2% 1/24 • From hospital admission to day of discharge for death, up to 60 days.
Respiratory, thoracic and mediastinal disorders Epistaxis	3.7% 1/27 • From hospital admission to day of discharge for death, up to 60 days.	0.00% 0/24 • From hospital admission to day of discharge for death, up to 60 days.
General disorders General disorders and administration site conditions - Other, specify	0.00% 0/27 • From hospital admission to day of discharge for death, up to 60 days.	4.2% 1/24 • From hospital admission to day of discharge for death, up to 60 days.
Renal and urinary disorders Hematuria	3.7% 1/27 • From hospital admission to day of discharge for death, up to 60 days.	4.2% 1/24 • From hospital admission to day of discharge for death, up to 60 days.
Metabolism and nutrition disorders Hypernatremia	3.7% 1/27 • From hospital admission to day of discharge for death, up to 60 days.	0.00% 0/24 • From hospital admission to day of discharge for death, up to 60 days.
Metabolism and nutrition disorders Hypoalbuminemia	11.1% 3/27 • From hospital admission to day of discharge for death, up to 60 days.	8.3% 2/24 • From hospital admission to day of discharge for death, up to 60 days.
Metabolism and nutrition disorders Hypocalcemia	3.7% 1/27 • From hospital admission to day of discharge for death, up to 60 days.	4.2% 1/24 • From hospital admission to day of discharge for death, up to 60 days.
Metabolism and nutrition disorders Hypoglycemia	3.7% 1/27 • From hospital admission to day of discharge for death, up to 60 days.	0.00% 0/24 • From hospital admission to day of discharge for death, up to 60 days.
Metabolism and nutrition disorders Hypokalemia	0.00% 0/27 • From hospital admission to day of discharge for death, up to 60 days.	4.2% 1/24 • From hospital admission to day of discharge for death, up to 60 days.
Metabolism and nutrition disorders Hypophosphatemia	0.00% 0/27 • From hospital admission to day of discharge for death, up to 60 days.	4.2% 1/24 • From hospital admission to day of discharge for death, up to 60 days.
Vascular disorders Hypotension	3.7% 1/27 • From hospital admission to day of discharge for death, up to 60 days.	0.00% 0/24 • From hospital admission to day of discharge for death, up to 60 days.
Gastrointestinal disorders Oral hemorrhage	3.7% 1/27 • From hospital admission to day of discharge for death, up to 60 days.	0.00% 0/24 • From hospital admission to day of discharge for death, up to 60 days.
Investigations Platelet count decreased	3.7% 1/27 • From hospital admission to day of discharge for death, up to 60 days.	0.00% 0/24 • From hospital admission to day of discharge for death, up to 60 days.
Nervous system disorders Seizure	3.7% 1/27 • From hospital admission to day of discharge for death, up to 60 days.	0.00% 0/24 • From hospital admission to day of discharge for death, up to 60 days.
Vascular disorders Thromboembolic event	3.7% 1/27 • From hospital admission to day of discharge for death, up to 60 days.	0.00% 0/24 • From hospital admission to day of discharge for death, up to 60 days.
Infections and infestations Tracheitis	3.7% 1/27 • From hospital admission to day of discharge for death, up to 60 days.	8.3% 2/24 • From hospital admission to day of discharge for death, up to 60 days.