DESIR-ABLE: Safety Study of Desirudin, an Anticoagulant for the Prophylaxis of Thrombosis

• Sponsor: Canyon Pharmaceuticals, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00913133
• Collaborator: (none)
• Enrollment: 516
• Locations: 16
• Arm: 1
• Duration (Months): 15
• Patients Per Site: 32.3
• Patients Per Site Per Month: 2.1

Study Details

Study Description

Brief Summary

The objective of this trial is to demonstrate the clinical utility of fixed-dose SC Desirudin for the prophylaxis of thrombosis as an alternative to heparin-based anticoagulation.

Condition or Disease	Intervention/Treatment	Phase
Thrombosis	Drug: Desirudin	Phase 4

Detailed Description

Hospitalized patients who require DVT prophylaxis and who are not good candidates for heparin-based anti-coagulation were eligible.

Study Design

• Study Type: Interventional
• Actual Enrollment: 516 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Multi-Center Trial of Desirudin for the Prophylaxis of Thrombosis: an Alternative to Heparin-Based Anticoagulation (DESIR-ABLE)
• Study Start Date: Mar 1, 2010
• Actual Primary Completion Date: Jun 1, 2011
• Actual Study Completion Date: Jun 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Desirudin desirudin 15 mg twice daily for a minimum of 5 days	Drug: Desirudin; Desirudin SC 15mg q12h; Other Names: Iprivask

Outcome Measures

Primary Outcome Measures

1. Major Bleeding [24 hours after last dose of study drug]

   Major bleeding is defined as clinically evident hemorrhage associated with a hemoglobin decrease ≥2 g/dL that leads to a transfusion of ≥2 units of whole blood or packed red cells outside of the peri-operative period (time from the start of the surgery or procedure and up to 12 hours after), or hemorrhage that is intracranial, retroperitoneal, or into a prosthetic joint.

Secondary Outcome Measures

1. Thrombosis [Up until 24 hours after last dose of study drug]

   New onset symptomatic thrombosis requiring medical or surgical intervention; Death due to thrombosis defined as fatal pulmonary embolism, ischemic stroke, mesenteric thrombosis or myocardial infarction.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Provide written informed consent before initiation of any study related procedures.

2. Be at least 18 years of age.

3. Patients requiring anticoagulation for the prophylaxis of thrombosis.

4. In the opinion of the Investigator, an alternative to heparin-based anticoagulant therapies is desirable.

Exclusion Criteria:

1. Confirmed pregnancy (if woman of child-bearing potential) (urine or serum pregnancy test).

2. Intracranial neoplasm, arteriovenous malformation or aneurysm.

3. Severe renal insufficiency (chronic or acute) with a GFR of < or equal to 30 mL/min as determined by measured or estimated creatinine clearance using Cockroft-Gault method or by estimated GFR using the MDRD formula.

4. Known allergy to desirudin or hirudin-derived drugs, or known sensitivity to any component of the product

5. Participation in other clinical research studies involving the evaluation of other investigational or FDA-approved drugs or devices within 30 days of enrollment (participation in observational studies of FDA-approved products is acceptable).

6. Refusal to undergo blood transfusion should it become necessary

7. Active bleeding or irreversible coagulation abnormality.

8. Uncontrolled hypertension defined as a blood pressure > or equal to 180/110 mmHg.

9. Patients requiring anticoagulation for left-ventricular assist device, intra-aortic balloon pump, veno-venous ultra filtration or ECMO.

10. Any other disease or condition which, in the judgment of the Investigator, would place a patient at undue risk by being enrolled in the trial, or cause inability to comply with the trial.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Colorado Health Science Center	Aurora	Colorado	United States	80045
2	University of South Florida, Tampa General Hospital	Tampa	Florida	United States	33606
3	Saint Joseph's Research Institute	Atlanta	Georgia	United States	30342
4	Southeastern Center for Clinical Trials	Decatur	Georgia	United States	30033
5	Provena St. Joseph's Medical Center	Joliet	Illinois	United States	60435
6	Illinois Lung and Critical Care Institute	Peoria	Illinois	United States	61606
7	St. John's Mercy Medical Center	St. Louis	Missouri	United States	63141
8	Overlook Hospital	Summit	New Jersey	United States	07901
9	Weill Cornell Medical College	New York	New York	United States	10065
10	Stony Brook University Medical Center	Stony Brook	New York	United States	11794-8191
11	Forsyth Regional Medical Center	Winston-Salem	North Carolina	United States	27103
12	Forsyth Regional Medical Center	Winston-Salem	North Carolina	United States	55902
13	The Ohio State University Medical Center	Columbus	Ohio	United States	43210
14	Drexel University College of Medicine	Philadelphia	Pennsylvania	United States	19102-1192
15	Research Concepts, Memorial Hermann Healthcare System	Houston	Texas	United States	77024
16	Carilion Roanoke Memorial Hospital	Roanoke	Virginia	United States	24014

Sponsors and Collaborators

• Canyon Pharmaceuticals, Inc.

Investigators

• Study Director: Dawn Bell, PharmD, Canyon Pharmaceuticals, Inc.
• Principal Investigator: Jerrold Levy, MD, FAHA, Emory University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Canyon Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT00913133
• Other Study ID Numbers: DES-09-02
• First Posted: Jun 4, 2009
• Last Update Posted: Jan 10, 2013
• Last Verified: Jan 1, 2013

• Keywords provided by Canyon Pharmaceuticals, Inc.: Anticoagulation; Prophylaxis; Desirudin; Direct thrombin inhibitor; Heparin-induced thrombocytopenia
• Additional relevant MeSH terms: Thrombosis; Desirudin

Study Results

Participant Flow

Recruitment Details	Patients were recruited between April 5, 2010 and February 18, 2011. Patients were recruited from inpatient medical and surgical services as well as surgical clinics when presenting for pre-operative services.

Arm/Group Title	Desirudin
Arm/Group Description	desirudin 15 mg twice daily for a minimum of 5 days
Period Title: Overall Study
STARTED	516
COMPLETED	516
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Desirudin
Arm/Group Description	desirudin 15 mg twice daily for a minimum of 5 days
Overall Participants	516
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	387 75%
>=65 years	129 25%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59 (14.7)
Sex: Female, Male (Count of Participants)
Female	314 60.9%
Male	202 39.1%
Region of Enrollment (participants) [Number]
United States	516 100%

Outcome Measures

1. Primary Outcome

Title	Major Bleeding
Description	Major bleeding is defined as clinically evident hemorrhage associated with a hemoglobin decrease ≥2 g/dL that leads to a transfusion of ≥2 units of whole blood or packed red cells outside of the peri-operative period (time from the start of the surgery or procedure and up to 12 hours after), or hemorrhage that is intracranial, retroperitoneal, or into a prosthetic joint.
Time Frame	24 hours after last dose of study drug

Outcome Measure Data

Analysis Population Description

All patients receiving at least one dose of study drug

Arm/Group Title	Desirudin
Arm/Group Description	desirudin 15 mg twice daily for a minimum of 5 days
Measure Participants	516
Number [participants]	0 0%

2. Secondary Outcome

Title	Thrombosis
Description	New onset symptomatic thrombosis requiring medical or surgical intervention; Death due to thrombosis defined as fatal pulmonary embolism, ischemic stroke, mesenteric thrombosis or myocardial infarction.
Time Frame	Up until 24 hours after last dose of study drug

Outcome Measure Data

Analysis Population Description

Patients who received at least one dose of study drug

Arm/Group Title	Desirudin
Arm/Group Description	desirudin 15 mg twice daily for a minimum of 5 days
Measure Participants	516
Number [participants]	8 1.6%

Adverse Events

Time Frame	up to 30 days after cessation of study drug
Arm/Group Title	Desirudin
Arm/Group Description	desirudin 15 mg twice daily for a minimum of 5 days
All Cause Mortality
	Desirudin
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Desirudin
	Affected / at Risk (%)	# Events
Total	80/516 (15.5%)
Blood and lymphatic system disorders
anemia	2/516 (0.4%)	2
leukopenia	1/516 (0.2%)	1
Cardiac disorders
acute myocardial infarction	4/516 (0.8%)	4
atrial fibrillation	5/516 (1%)	5
cardiac failure congestive	2/516 (0.4%)	2
cardiogenic shock	1/516 (0.2%)	1
coronary artery disease	1/516 (0.2%)	1
Gastrointestinal disorders
abdominal distension	1/516 (0.2%)	1
abdominal pain	2/516 (0.4%)	2
colonic obstruction	1/516 (0.2%)	1
constipation	3/516 (0.6%)	3
gastric hemorrhage	4/516 (0.8%)	4
gastrointestinal necrosis	1/516 (0.2%)	1
hematemesis	1/516 (0.2%)	1
ileus	1/516 (0.2%)	1
nausea	2/516 (0.4%)	2
pancreatic pseudocyst	1/516 (0.2%)	1
rectal hemorrhage	1/516 (0.2%)	1
small intestinal obstruction	7/516 (1.4%)	7
vomiting	1/516 (0.2%)	1
General disorders
asthenia	1/516 (0.2%)	1
multi-organ failure	2/516 (0.4%)	2
Hepatobiliary disorders
cholecystitis acute	1/516 (0.2%)	1
Infections and infestations
abdominal abscess	1/516 (0.2%)	1
abdominal sepsis	1/516 (0.2%)	1
bacterial infection	1/516 (0.2%)	1
cellulitis	1/516 (0.2%)	1
clostridium difficile colitis	2/516 (0.4%)	2
diverticulitis	1/516 (0.2%)	1
osteomyelitis	1/516 (0.2%)	1
pelvic abscess	1/516 (0.2%)	1
peridiverticular abscess	1/516 (0.2%)	1
pneumonia	2/516 (0.4%)	2
post-procedural infection	1/516 (0.2%)	1
sepsis	3/516 (0.6%)	3
septic shock	1/516 (0.2%)	1
wound infection	1/516 (0.2%)	1
Injury, poisoning and procedural complications
gatrointestinal disorder postoperative	1/516 (0.2%)	1
gastrointestinal stoma complication	1/516 (0.2%)	1
graft thrombosis	1/516 (0.2%)	1
postoperative ileus	5/516 (1%)	5
procedural nausea	1/516 (0.2%)	1
procedural pain	1/516 (0.2%)	1
procedural site reaction	1/516 (0.2%)	1
procedural vomiting	1/516 (0.2%)	1
splenic hematoma	1/516 (0.2%)	1
subdural hematoma	1/516 (0.2%)	1
Investigations
white blood cell count increased	1/516 (0.2%)	1
Metabolism and nutrition disorders
dehydration	1/516 (0.2%)	1
failure to thrive	1/516 (0.2%)	1
Musculoskeletal and connective tissue disorders
pain in extremity	1/516 (0.2%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
bladder cancer	1/516 (0.2%)	1
lung neoplasm malignant	1/516 (0.2%)	1
plasmacytoma	1/516 (0.2%)	1
Nervous system disorders
embolic stroke	1/516 (0.2%)	1
syncope	3/516 (0.6%)	3
Renal and urinary disorders
hydronephrosis	1/516 (0.2%)	1
renal failure	3/516 (0.6%)	3
renal failure acute	5/516 (1%)	5
uretic obstruction	1/516 (0.2%)	1
Reproductive system and breast disorders
pelvic fluid collection	1/516 (0.2%)	1
pelvic pain	1/516 (0.2%)	1
vaginal hemorrhage	1/516 (0.2%)	1
Respiratory, thoracic and mediastinal disorders
atelectasis	1/516 (0.2%)	1
bronchial secretion retention	1/516 (0.2%)	1
chronic obstructive pulmonary disease	1/516 (0.2%)	1
diaphragmatic hernia	1/516 (0.2%)	1
dyspnea	1/516 (0.2%)	1
hypoxia	1/516 (0.2%)	1
pleural effusion	4/516 (0.8%)	4
pneumonia aspiration	1/516 (0.2%)	1
pulmonary embolism	1/516 (0.2%)	1
pulmonary oedema	1/516 (0.2%)	1
respiratory failure	4/516 (0.8%)	4
Surgical and medical procedures
cholecystectomy	1/516 (0.2%)	1
Vascular disorders
deep vein thrombosis	3/516 (0.6%)	3
haematoma	1/516 (0.2%)	1
Other (Not Including Serious) Adverse Events
	Desirudin
	Affected / at Risk (%)	# Events
Total	382/516 (74%)
Blood and lymphatic system disorders
anemia	45/516 (8.7%)	45
Cardiac disorders
tachycardia	37/516 (7.2%)	37
hypotension	27/516 (5.2%)	27
Gastrointestinal disorders
constipation	76/516 (14.7%)	76
nausea	76/516 (14.7%)	76
vomiting	31/516 (6%)	31
General disorders
pyrexia	39/516 (7.6%)	39
asthenia	36/516 (7%)	36
generalised oedema	26/516 (5%)	26
Injury, poisoning and procedural complications
procedural pain	59/516 (11.4%)	59
anemia postoperative	33/516 (6.4%)	33
Metabolism and nutrition disorders
hypophosphataemia	38/516 (7.4%)	38
hyperglycemia	30/516 (5.8%)	30
hypokalemia	27/516 (5.2%)	27
hypocalcemia	26/516 (5%)	26
Respiratory, thoracic and mediastinal disorders
breath sounds abnormal	41/516 (7.9%)	41
oxygen saturation decrease	32/516 (6.2%)	32
Vascular disorders
oedema peripheral	31/516 (6%)	31

Limitations/Caveats

This was a multi-center, single-arm, observational safety trial. The lack of an active comparator does not allow us to make conclusions about the relative safety and efficacy of the product.

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 less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.