The Safety and Effectiveness of PROCRIT (Epoetin Alfa) in Patients Undergoing Elective Major Abdominal and/or Pelvic Surgery

• Sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00350519
• Collaborator: Ortho Biotech Clinical Affairs, L.L.C. (Industry)
• Enrollment: 37
• Arms: 2
• Duration (Months): 18

Study Details

Study Description

Brief Summary

The primary purpose of the study is to compare the effect of perioperative (the time period describing the duration of a participants surgical procedure) administration of PROCRIT to that of Standard of Care (SOC) on the proportion of participants receiving pRBC (packed red blood cells) transfusions (from the day of surgery to the day of hospital discharge) in participants undergoing elective major abdominal and/or pelvic surgery. Standard of Care is defined as the treatment of participants according to the hospital or institution's policy, but where participants will not receive PROCRIT (Epoetin alfa) or any other erythropoiesis-stimulating agents (ESAs) (agents that stimulate the production of red blood cells in the bone marrow).

Condition or Disease	Intervention/Treatment	Phase
Hemostasis, Surgical	Drug: Epoetin alfa; Drug: Standard of Care	Phase 4

Detailed Description

This is a randomized (the study medication is assigned by chance), parallel-arm (each group of participants will be treated at the same time), open-label (all people know the identity of the intervention), multicenter study. The study consists of screening phase of 21 days, treatment phase of 15 days, follow-up phase of 28 days. Approximately 110 participants undergoing elective major abdominal and/or pelvic surgery will be enrolled. During the Treatment Phase, eligible participants will be randomly assigned (participants are assigned to a treatment group based on chance) in a 1:1 ratio to either PROCRIT (Epoetin alfa) or the Standard of Care (SOC) group that will not receive any erythropoiesis-stimulating agents (ESAs). Participants will undergo surgery during the Treatment Phase. After surgery, all participants will stay in the study for 4 days (or until hospital discharge) and followed for an additional 28 days (Follow-up Phase). Safety evaluations will include assessment of adverse events, clinical laboratory tests, electrocardiogram, vital signs, and physical examination which will be monitored throughout the study. The duration of the study for each participant will be approximately 64 days.

Study Design

• Study Type: Interventional
• Actual Enrollment: 37 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open Label, Multicenter, Randomized, Controlled Study to Evaluate Efficacy and Safety of PROCRIT in Subjects Undergoing Elective Major Abdominal and/or Pelvic Surgery
• Study Start Date: Aug 1, 2006
• Actual Primary Completion Date: Feb 1, 2008
• Actual Study Completion Date: Feb 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PROCRIT (epoetin alfa) Participants will receive PROCRIT (epoetin alfa).	Drug: Epoetin alfa; Participants will receive epoetin alfa 300 IU/kg once daily subcutaneously for 10 days prior to surgery, on the day of surgery, and for four days after surgery.; Other Names: PROCRIT
Experimental: STANDARD THERAPY Participants will receive standard of care.	Drug: Standard of Care; Participants will receive standard of care based on the Institution's treatment policy.

Outcome Measures

Primary Outcome Measures

1. Number of Participants Receiving pRBC (Packed Red Blood Cell) Transfusions [Day of surgery until hospital discharge]

Secondary Outcome Measures

1. Hemoglobin Change From Baseline to End of Study [Baseline (Day-10) to end of study (Day 32)]

   End of Study Hemoglobin minus baseline Hemoglobin

2. Number of pRBC Units Transfused During Study [Baseline (Day -10) to end of study (Day 32)]

3. Hospital Length of Stay [Surgery to hospital discharge]

Eligibility Criteria

Criteria

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

Inclusion Criteria: - Scheduled to undergo elective major abdominal and/or pelvic surgery with anticipated significant perioperative ((the time period describing the duration of a participants surgical procedure) blood loss (eg, greater than 500 cc and at increased risk for blood transfusion) - Hemoglobin greater than 10 g/dL and less than or equal to 13 g/dL at screening (Day -13 [13 days prior to surgery] to Day -11) and baseline (Day -10) - Patients with reproductive potential and their partners must practice an effective method of birth control (eg, prescription oral contraceptives, contraceptive injections, intrauterine device, double-barrier method, contraceptive patch, partner sterilization) before entry and throughout the study - Female patients with reproductive potential must have a negative urine pregnancy test within 7 days of the first dose of PROCRIT - Adequate renal (kidney) and adequate hepatic (liver) function assessed within the 21-day screening period Exclusion Criteria: - No severe Congestive Heart Failure (New York Heart Association Class IV) - No known severe stable or unstable coronary artery disease, or unstable angina

• No history of deep venous thrombosis (DVT) or pulmonary embolus (PE) within 12 months before study entry (prior superficial thrombophlebitis is not an exclusion criterion) - No history of cerebrovascular accident (CVA), transient ischemic attack (TIA), Acute coronary syndrome (unstable Angina, myocardial Infarction), or other arterial thrombosis within 6 months before study entry - Not anticipated to donate perioperative autologous blood or receive transfusions within 21 days prior to baseline or to have greater than 6 transfusions perioperatively - No prior treatment with PROCRIT or any erythropoiesis-stimulating agents (ESAs) within the previous month

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
• Ortho Biotech Clinical Affairs, L.L.C.

Investigators

• Study Director: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial, Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
• ClinicalTrials.gov Identifier: NCT00350519
• Other Study ID Numbers: CR012460; EPOSUR4005
• First Posted: Jul 10, 2006
• Last Update Posted: Jul 22, 2013
• Last Verified: Jul 1, 2013

• Keywords provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.: Hemostasis, Surgical; Epoetin alfa; Surgery; Abdomen; Pelvis; PROCRIT; pRBC; Blood transfusion; Packed red blood cell transfusion
• Additional relevant MeSH terms: Epoetin Alfa

Study Results

Participant Flow

Pre-assignment Detail	37 participants were enrolled in the study. 18 participants were randomly assigned to the epoetin alfa group and 19 were randomly assigned to the Standard therapy group.

Arm/Group Title	PROCRIT (Epoetin Alfa)	STANDARD THERAPY
Arm/Group Description	Participants received epoetin alfa 300 IU/kg subcutaneously once daily for 10 days, prior to surgery, on the day of surgery, and for four days after surgery	Participants received standard of care based on the Institution's treatment policy
Period Title: Overall Study
STARTED	18	19
COMPLETED	14	13
NOT COMPLETED	4	6

Baseline Characteristics

Arm/Group Title	PROCRIT (Epoetin Alfa)	STANDARD THERAPY	Total
Arm/Group Description	Participants received epoetin alfa 300 IU/kg subcutaneously once daily for 10 days, prior to surgery, on the day of surgery, and for four days after surgery	Participants received standard of care based on the Institution's treatment policy	Total of all reporting groups
Overall Participants	18	19	37
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	11 61.1%	12 63.2%	23 62.2%
>=65 years	7 38.9%	7 36.8%	14 37.8%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.06 (16.17)	61.42 (18.32)	62.22 (17.08)
Sex: Female, Male (Count of Participants)
Female	13 72.2%	10 52.6%	23 62.2%
Male	5 27.8%	9 47.4%	14 37.8%
Race/Ethnicity, Customized (participants) [Number]
Black or Aftrican American	0 0%	5 26.3%	5 13.5%
Other	1 5.6%	2 10.5%	3 8.1%
White	17 94.4%	12 63.2%	29 78.4%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Receiving pRBC (Packed Red Blood Cell) Transfusions
Time Frame	Day of surgery until hospital discharge

Outcome Measure Data

Analysis Population Description

ITT(intention to treat), No formal analysis was conducted due to early termination and small sample size

Arm/Group Title	PROCRIT (Epoetin Alfa)	STANDARD THERAPY
Arm/Group Description	Participants received epoetin alfa 300 IU/kg subcutaneously once daily for 10 days, prior to surgery, on the day of surgery, and for four days after surgery	Participants received standard of care based on the Institution's treatment policy
Measure Participants	18	19
Number [participants]	4 22.2%	9 47.4%

2. Secondary Outcome

Title	Hemoglobin Change From Baseline to End of Study
Description	End of Study Hemoglobin minus baseline Hemoglobin
Time Frame	Baseline (Day-10) to end of study (Day 32)

Outcome Measure Data

Analysis Population Description

All Subjects, No formal analysis was conducted due to early termination and small sample size

Arm/Group Title	PROCRIT (Epoetin Alfa)	STANDARD THERAPY
Arm/Group Description	Participants received epoetin alfa 300 IU/kg subcutaneously once daily for 10 days, prior to surgery, on the day of surgery, and for four days after surgery	Participants received standard of care based on the Institution's treatment policy
Measure Participants	13	13
Mean (Standard Deviation) [g/dL]	0.98 (1.39)	0.33 (2.06)

3. Secondary Outcome

Title	Number of pRBC Units Transfused During Study
Time Frame	Baseline (Day -10) to end of study (Day 32)

Outcome Measure Data

Analysis Population Description

ITT, No formal analysis was conducted due to early termination and small sample size

Arm/Group Title	PROCRIT (Epoetin Alfa)	STANDARD THERAPY
Arm/Group Description	Participants received epoetin alfa 300 IU/kg subcutaneously once daily for 10 days, prior to surgery, on the day of surgery, and for four days after surgery	Participants received standard of care based on the Institution's treatment policy
Measure Participants	4	9
Mean (Standard Deviation) [units]	3.5 (3.00)	6.11 (7.98)

4. Secondary Outcome

Title	Hospital Length of Stay
Time Frame	Surgery to hospital discharge

Outcome Measure Data

Analysis Population Description

ITT, No formal analysis was conducted due to early termination and small sample size

Arm/Group Title	PROCRIT (Epoetin Alfa)	STANDARD THERAPY
Arm/Group Description	Participants received epoetin alfa 300 IU/kg subcutaneously once daily for 10 days, prior to surgery, on the day of surgery, and for four days after surgery	Participants received standard of care based on the Institution's treatment policy
Measure Participants	17	16
Mean (Standard Deviation) [days]	7.94 (5.17)	12.56 (12.30)

Adverse Events

Time Frame	64 days
Arm/Group Title	PROCRIT (Epoetin Alfa)		STANDARD THERAPY
Arm/Group Description	Participants received epoetin alfa 300 IU/kg subcutaneously once daily for 10 days, prior to surgery, on the day of surgery, and for four days after surgery		Participants received standard of care based on the Institution's treatment policy
All Cause Mortality
	PROCRIT (Epoetin Alfa)		STANDARD THERAPY
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	PROCRIT (Epoetin Alfa)		STANDARD THERAPY
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/18 (27.8%)		8/19 (42.1%)
Infections and infestations
Abdominal abscess	1/18 (5.6%)		0/19 (0%)
Injury, poisoning and procedural complications
Device dislocation	0/18 (0%)		1/19 (5.3%)
Postoperative ileus	2/18 (11.1%)		0/19 (0%)
Wound dehiscence	1/18 (5.6%)		0/19 (0%)
Investigations
Anticoagulation drug level below therapurtic	0/18 (0%)		1/19 (5.3%)
International normalized ratio increased	0/18 (0%)		1/19 (5.3%)
Metabolism and nutrition disorders
Failure to thrive	0/18 (0%)		2/19 (10.5%)
Hypergylcaemia	0/18 (0%)		1/19 (5.3%)
Malnutrition	0/18 (0%)		1/19 (5.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer metastatic	0/18 (0%)		1/19 (5.3%)
Metastatic neoplasm	0/18 (0%)		1/19 (5.3%)
Pancreatic carcinoma	0/18 (0%)		1/19 (5.3%)
Renal and urinary disorders
Renal failure	1/18 (5.6%)		0/19 (0%)
Ureteric obstruction	1/18 (5.6%)		0/19 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	0/18 (0%)		1/19 (5.3%)
Hypoxia	0/18 (0%)		1/19 (5.3%)
Pleural effusion	1/18 (5.6%)		0/19 (0%)
Pneumonitis	0/18 (0%)		1/19 (5.3%)
Stridor	0/18 (0%)		1/19 (5.3%)
Vascular disorders
Thrombosis	0/18 (0%)		1/19 (5.3%)
Other (Not Including Serious) Adverse Events
	PROCRIT (Epoetin Alfa)		STANDARD THERAPY
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/18 (100%)		13/19 (68.4%)
Blood and lymphatic system disorders
Anaemia	0/18 (0%)		2/19 (10.5%)
Thrombocytopenia	0/18 (0%)		2/19 (10.5%)
Cardiac disorders
Atrial fibrillation	0/18 (0%)		1/19 (5.3%)
Sinus tachycardia	1/18 (5.6%)		1/19 (5.3%)
Supraventricular tachycardia	1/18 (5.6%)		0/19 (0%)
Tachycardia	2/18 (11.1%)		2/19 (10.5%)
Gastrointestinal disorders
Abdominal distension	1/18 (5.6%)		0/19 (0%)
Abdominal pain	2/18 (11.1%)		1/19 (5.3%)
Constipation	1/18 (5.6%)		0/19 (0%)
Diarrhoea	1/18 (5.6%)		1/19 (5.3%)
Diverticulum	1/18 (5.6%)		0/19 (0%)
Duodenal ulcer	0/18 (0%)		1/19 (5.3%)
Faecaloma	1/18 (5.6%)		0/19 (0%)
Ileus	0/18 (0%)		1/19 (5.3%)
Nausea	6/18 (33.3%)		6/19 (31.6%)
Pancreatic fistula	1/18 (5.6%)		1/19 (5.3%)
Stomach discomfort	1/18 (5.6%)		0/19 (0%)
Vomiting	4/18 (22.2%)		2/19 (10.5%)
Faeces discoloured	1/18 (5.6%)		0/19 (0%)
General disorders
Asthenia	1/18 (5.6%)		0/19 (0%)
Feeling hot	1/18 (5.6%)		0/19 (0%)
Oedema peripheral	0/18 (0%)		1/19 (5.3%)
Pain	2/18 (11.1%)		1/19 (5.3%)
Pyrexia	2/18 (11.1%)		7/19 (36.8%)
Infections and infestations
Application site infection	1/18 (5.6%)		0/19 (0%)
Bacterial infection	0/18 (0%)		1/19 (5.3%)
Pneumonia	0/18 (0%)		1/19 (5.3%)
Rhinitis	1/18 (5.6%)		0/19 (0%)
Staphylococcal infection	1/18 (5.6%)		0/19 (0%)
Tracheobronchitis	0/18 (0%)		1/19 (5.3%)
Injury, poisoning and procedural complications
Contusion	1/18 (5.6%)		0/19 (0%)
Head injury	1/18 (5.6%)		0/19 (0%)
Incision site complication	1/18 (5.6%)		1/19 (5.3%)
Muscle strain	1/18 (5.6%)		0/19 (0%)
Postoperative ileus	0/18 (0%)		1/19 (5.3%)
Procedural hypertension	1/18 (5.6%)		3/19 (15.8%)
Procedural hypotension	3/18 (16.7%)		5/19 (26.3%)
Wound dehiscence	0/18 (0%)		2/19 (10.5%)
Procedural pain	2/18 (11.1%)		5/19 (26.3%)
Investigations
Blood potassium decreased	0/18 (0%)		1/19 (5.3%)
Body temperature increased	0/18 (0%)		1/19 (5.3%)
Platelet count increased	0/18 (0%)		1/19 (5.3%)
Prothrombin level increased	0/18 (0%)		1/19 (5.3%)
Prothrombin time prolonged	1/18 (5.6%)		0/19 (0%)
Urine output decreased	1/18 (5.6%)		2/19 (10.5%)
Metabolism and nutrition disorders
Cachexia	0/18 (0%)		1/19 (5.3%)
Dehydration	0/18 (0%)		1/19 (5.3%)
Diabetes mellitus	1/18 (5.6%)		0/19 (0%)
Hyperglycaemia	1/18 (5.6%)		3/19 (15.8%)
Hypokalaemia	1/18 (5.6%)		1/19 (5.3%)
Hypomagnesaemia	0/18 (0%)		1/19 (5.3%)
Metabolic acidosis	0/18 (0%)		1/19 (5.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/18 (5.6%)		0/19 (0%)
Back pain	1/18 (5.6%)		0/19 (0%)
Musculoskeletal chest pain	1/18 (5.6%)		0/19 (0%)
Shoulder pain	1/18 (5.6%)		0/19 (0%)
Nervous system disorders
Dizziness	1/18 (5.6%)		1/19 (5.3%)
Headache	2/18 (11.1%)		0/19 (0%)
Lethargy	0/18 (0%)		2/19 (10.5%)
Psychiatric disorders
Agitation	0/18 (0%)		1/19 (5.3%)
Anxiety	1/18 (5.6%)		0/19 (0%)
Confusional state	1/18 (5.6%)		1/19 (5.3%)
Hallucination	1/18 (5.6%)		0/19 (0%)
Insomnia	1/18 (5.6%)		0/19 (0%)
Mental status changes	1/18 (5.6%)		0/19 (0%)
Renal and urinary disorders
Dysuria	0/18 (0%)		1/19 (5.3%)
Haematuria	1/18 (5.6%)		0/19 (0%)
Renal failure	1/18 (5.6%)		0/19 (0%)
Renal tubular necrosis	0/18 (0%)		1/19 (5.3%)
Urinary retention	1/18 (5.6%)		0/19 (0%)
Respiratory, thoracic and mediastinal disorders
Atelectasis	1/18 (5.6%)		1/19 (5.3%)
Cough	3/18 (16.7%)		2/19 (10.5%)
Dyspnoea	0/18 (0%)		2/19 (10.5%)
Hypoxia	1/18 (5.6%)		1/19 (5.3%)
Laryngeal oedema	0/18 (0%)		1/19 (5.3%)
Lung consolidation	1/18 (5.6%)		0/19 (0%)
Pharyngolaryngeal pain	0/18 (0%)		1/19 (5.3%)
Pleural effusion	1/18 (5.6%)		1/19 (5.3%)
Pneumothorax	0/18 (0%)		1/19 (5.3%)
Pulmonary congestion	1/18 (5.6%)		0/19 (0%)
Respiratory distress	0/18 (0%)		1/19 (5.3%)
Respiratory failure	1/18 (5.6%)		1/19 (5.3%)
Rhinorrhoea	1/18 (5.6%)		0/19 (0%)
Throat irritation	1/18 (5.6%)		0/19 (0%)
Wheezing	1/18 (5.6%)		2/19 (10.5%)
Skin and subcutaneous tissue disorders
Skin odour abnormal	0/18 (0%)		1/19 (5.3%)
Skin ulcer	1/18 (5.6%)		0/19 (0%)
Surgical and medical procedures
Wound drainage	0/18 (0%)		1/19 (5.3%)
Vascular disorders
Hypertension	0/18 (0%)		1/19 (5.3%)
Hypotension	4/18 (22.2%)		1/19 (5.3%)

Limitations/Caveats

No formal analysis was conducted due to early termination.

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.