Study Evaluating Refacto For Pharmacovigilance

• Sponsor: Wyeth is now a wholly owned subsidiary of Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00195442
• Collaborator: (none)
• Enrollment: 288
• Locations: 26
• Duration (Months): 126.1
• Patients Per Site: 11.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to investigate the effectiveness and safety of treatment with ReFacto under conditions of routine therapy. Furthermore a continuous benefit/risk assessment will be done.

Condition or Disease	Intervention/Treatment	Phase
Hemophilia A	Drug: Moroctocog alfa

Detailed Description

Non-interventional study: subjects to be selected according to the usual clinical practice of their physician

Study Design

• Study Type: Observational
• Actual Enrollment: 288 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Pharmacovigilance Evaluation Of Refacto In Usual Care Settings
• Study Start Date: Jul 1, 1999
• Actual Primary Completion Date: Jan 1, 2010
• Actual Study Completion Date: Jan 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
A Patients with Hemophilia A	Drug: Moroctocog alfa; Patients will be treated in accordance with the requirements of the labeling of ReFacto (Moroctocog alfa) in Germany. The dosage and duration of therapy is to be determined by the physician to meet the patients' individual needs for treatment.; Other Names: ReFacto

Outcome Measures

Primary Outcome Measures

1. Mean Number of Bleeding Episodes Per Patient Year [Baseline up to a mean duration of 54 months]

   Participants with hemophilia A suffer from a hereditary lack of blood clotting factor VIII. As a consequence, the ability of the blood to coagulate is reduced and bleedings at any site or organ of the body may occur after minor injury or even spontaneously. Predominantly, joints, muscles, and internal organs are affected by bleeding complications. Participants reported the occurrence of each bleeding episode while on study. The bleeding rate for each participant was calculated by number of reported episodes per years on study.

2. Mean Number of Bleeding-related Exposure Days Per Patient Year [Baseline up to a mean duration of 54 months]

   Exposure days are the number of days of treatment with ReFacto.

3. Mean Number of Exposure Days Per Patient Year [Baseline up to a mean duration of 54 months]

   Exposure days are the number of days of treatment with ReFacto.

Secondary Outcome Measures

1. Number of Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) [Baseline up to a mean duration of 54 months]

   AEs are any undesired side effect which occurred in a participant undergoing study treatment independent of whether a correlation with study treatment was suspected or not. SAEs are undesired events which were lethal or life-threatening, made hospitalization or extension of hospital stay necessary, lead to permanent damage with handicap (inability to work), as well as congenital anomalies, malignant disease, or overdosing. Also presence of inhibitors, thrombotic events, erythrocyte agglutination, allergic reactions, less than therapeutic effect, and inhibitor development were considered SAEs.

2. Number of Participants With de Novo Inhibitor Formation [Baseline up to a mean duration of 54 months]

   The applied criteria of clinical relevance for de novo inhibitor formation was defined as normal Factor VIII dosage was ineffective to control a bleeding, control of bleeding episodes required increasing Factor VIII dosage, change of concentrate type (administration of activated Prothrombin-Complex Concentrate [aPCC] or recombinant Factor VII [rFVII ]) was needed to stop a bleeding, or change of therapy strategy (intensive prophylaxis or Immune Tolerance Induction [ITI]) was required.

3. Mean Annual ReFacto Consumption Per Patient Year [Baseline up to a mean duration of 54 months]

   ReFacto administered as International Units (IU) according to the physician's decision following the drug's summary of product characteristics (SPC) and according to usual care principles.

4. Number of Participants for Physicians' Assessment of Satisfaction With Treatment Success [Baseline up to a mean duration of 54 months]

   Subjective assessment by the physician to evaluate treatment success (i.e., control of bleeding, Factor VIII consumption, treatment efficacy and tolerance, handling of preparation, and days missing from work or school). Physician rated assessment could be categorized as Very satisfied, Satisfied, Unsatisfied, or Very unsatisfied; no criteria was pre-specified for the assessment categories in this observational study.

5. Number of Participants for Physicians' Assessment of Efficacy [Baseline up to a mean duration of 54 months]

   Subjective assessment by the physician to evaluate control of bleeding. Physician rated assessment could be categorized as Very good, Good, Moderate, or Poor; no criteria was pre-specified for the assessment categories in this observational study.

6. Number of Participants for Patients' Assessment of Efficacy [Baseline up to a mean duration of 54 months]

   Subjective assessment by the participant to evaluate control of bleeding. Patient rated assessment could be categorized as Very good, Good, Moderate, Poor, or No specification; no criteria was pre-specified for the assessment categories in this observational study.

7. Number of Participants for Physicians' Assessment of Tolerance [Baseline up to a mean duration of 54 months]

   Subjective assessment by the physician to evaluate the participants' tolerance of treatment with ReFacto (i.e., dose, administration method, or adverse effects). Physician rated assessment could be categorized as Very good, Good, Moderate, or Poor; no criteria was pre-specified for the assessment categories in this observational study.

8. Number of Participants for Patients' Assessment of Tolerance [Baseline up to a mean duration of 54 months]

   Subjective assessment by the participant to evaluate tolerance of treatment with ReFacto (i.e., dose, administration method, or adverse effects). Patient rated assessment could be categorized as Very good, Good, Moderate, Poor, or No specification; no criteria was pre-specified for the assessment categories in this observational study.

9. Number of Participants for Physicians' Assessment of Handling of ReFacto [Baseline up to a mean duration of 54 months]

   Subjective assessment by the physician to evaluate the participants' handling (preparation and administration) of ReFacto. Physician rated assessment could be categorized as Very good, Good, Moderate, or Poor; no criteria was pre-specified for the assessment categories in this observational study.

10. Number of Participants for Patients' Assessment of Handling of ReFacto [Baseline up to a mean duration of 54 months]

    Subjective assessment by the participant on handling (preparation and administration) of ReFacto. Patient rated assessment could be categorized as Very good, Good, Moderate, Poor, or No specification; no criteria was pre-specified for the assessment categories in this observational study.

11. Number of Participants for Days of Sick Leave Per Month [Baseline up to a mean duration of 54 months]

    Days of sick leave (missing work or school) per month categorized as No days of absence, Number of days of absence, Long-term inability to work or study, Not employed or at school, or No specification.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Proven diagnosis of Hemophilia A

Exclusion Criteria:

• Contraindications according to Summary of Product Characteristics

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	Vienna		Austria	A-1090
2	Pfizer Investigational Site	Frankfurt	Hessen	Germany	60596
3	Pfizer Investigational Site	Giessen	Hessen	Germany	35385
4	Pfizer Investigational Site	Rostock	Mecklenburg-Vorpommern	Germany	18055
5	Pfizer Investigational Site	Hannover	Niedersachsen	Germany	30625
6	Pfizer Investigational Site	Bonn	Nordrhein-Westfalen	Germany	53105
7	Pfizer Investigational Site	Halle	Sachsen-Anhalt	Germany	06120
8	Pfizer Investigational Site	Stadtroda	Thuringen	Germany	07646
9	Pfizer Investigational Site	Berlin		Germany	10249
10	Pfizer Investigational Site	Berlin		Germany	13353
11	Pfizer Investigational Site	Bermen		Germany	28205
12	Pfizer Investigational Site	Erlangen		Germany	91054
13	Pfizer Investigational Site	Frankfurt a. M.		Germany	60594
14	Pfizer Investigational Site	Hamburg		Germany	20246
15	Pfizer Investigational Site	Heidelberg		Germany	69123
16	Pfizer Investigational Site	Homburg		Germany	66424
17	Pfizer Investigational Site	Klipphausen		Germany	01665
18	Pfizer Investigational Site	Leipzig		Germany	04103
19	Pfizer Investigational Site	Lubeck		Germany	23538
20	Pfizer Investigational Site	Muenchen		Germany	80336
21	Pfizer Investigational Site	Muenchen		Germany	80337
22	Pfizer Investigational Site	Muenster		Germany	D-48143
23	Pfizer Investigational Site	Potsdam		Germany	14467
24	Pfizer Investigational Site	Schwerin		Germany	19049
25	Pfizer Investigational Site	Ulm		Germany	89081
26	Pfizer Investigational Site	Wiesbaden		Germany	65191

Sponsors and Collaborators

• Wyeth is now a wholly owned subsidiary of Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00195442
• Other Study ID Numbers: 3082A-100690
• First Posted: Sep 19, 2005
• Last Update Posted: Feb 11, 2011
• Last Verified: Feb 1, 2011

• Keywords provided by , ,: Hemophilia A
• Additional relevant MeSH terms: Hemophilia A; Factor VIII

Study Results

Participant Flow

Recruitment Details	A total of 288 participants were observed during the study in 48 centers (44 Germany and 4 Austria) from time of First subject first visit May 1999 to Last subject last visit January 2010.
Pre-assignment Detail	The study was terminated January 2010 due to the introduction of a successor product ReFacto® AF.

Arm/Group Title	ReFacto (Moroctocog Alfa)
Arm/Group Description	B-domain deleted, recombinant factor VIII (BDDrFVIII) for participants with Hemophilia A in usual health care settings.
Period Title: Overall Study
STARTED	288
COMPLETED	152
NOT COMPLETED	136

Baseline Characteristics

Arm/Group Title	ReFacto (Moroctocog Alfa)
Arm/Group Description	B-domain deleted, recombinant factor VIII (BDDrFVIII) for participants with Hemophilia A in usual health care settings.
Overall Participants	288
Age, Customized (participants) [Number]
Children < 18 years of age	106 36.8%
Adults ≥ 18 years of age	182 63.2%
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	288 100%

Outcome Measures

1. Primary Outcome

Title	Mean Number of Bleeding Episodes Per Patient Year
Description	Participants with hemophilia A suffer from a hereditary lack of blood clotting factor VIII. As a consequence, the ability of the blood to coagulate is reduced and bleedings at any site or organ of the body may occur after minor injury or even spontaneously. Predominantly, joints, muscles, and internal organs are affected by bleeding complications. Participants reported the occurrence of each bleeding episode while on study. The bleeding rate for each participant was calculated by number of reported episodes per years on study.
Time Frame	Baseline up to a mean duration of 54 months

Outcome Measure Data

Analysis Population Description

Total population for efficacy analysis included all participants with submitted diary cards and severe haemophilia.

Arm/Group Title	ReFacto (Moroctocog Alfa)
Arm/Group Description	B-domain deleted, recombinant factor VIII (BDDrFVIII) for participants with Hemophilia A in usual health care settings.
Measure Participants	192
Mean (Standard Deviation) [episodes per year]	13.41 (14.67)

2. Primary Outcome

Title	Mean Number of Bleeding-related Exposure Days Per Patient Year
Description	Exposure days are the number of days of treatment with ReFacto.
Time Frame	Baseline up to a mean duration of 54 months

Outcome Measure Data

Analysis Population Description

Total population for efficacy analysis included all participants with submitted diary cards and severe haemophilia.

Arm/Group Title	ReFacto (Moroctocog Alfa)
Arm/Group Description	B-domain deleted, recombinant factor VIII (BDDrFVIII) for participants with Hemophilia A in usual health care settings.
Measure Participants	192
Mean (Standard Deviation) [days per year]	20.58 (21.39)

3. Primary Outcome

Title	Mean Number of Exposure Days Per Patient Year
Description	Exposure days are the number of days of treatment with ReFacto.
Time Frame	Baseline up to a mean duration of 54 months

Outcome Measure Data

Analysis Population Description

Total population for efficacy analysis included all participants with submitted diary cards and severe haemophilia.

Arm/Group Title	ReFacto (Moroctocog Alfa)
Arm/Group Description	B-domain deleted, recombinant factor VIII (BDDrFVIII) for participants with Hemophilia A in usual health care settings.
Measure Participants	192
Mean (Standard Deviation) [days per year]	126.76 (68.81)

4. Secondary Outcome

Title	Number of Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description	AEs are any undesired side effect which occurred in a participant undergoing study treatment independent of whether a correlation with study treatment was suspected or not. SAEs are undesired events which were lethal or life-threatening, made hospitalization or extension of hospital stay necessary, lead to permanent damage with handicap (inability to work), as well as congenital anomalies, malignant disease, or overdosing. Also presence of inhibitors, thrombotic events, erythrocyte agglutination, allergic reactions, less than therapeutic effect, and inhibitor development were considered SAEs.
Time Frame	Baseline up to a mean duration of 54 months

Outcome Measure Data

Analysis Population Description

Safety population includes all subjects with a baseline visit; (n)=number of participants with events.

Arm/Group Title	ReFacto (Moroctocog Alfa)
Arm/Group Description	B-domain deleted, recombinant factor VIII (BDDrFVIII) for participants with Hemophilia A in usual health care settings.
Measure Participants	288
Non-serious Adverse Events (n=118)	668
Serious Adverse Events (n=141)	291

5. Secondary Outcome

Title	Number of Participants With de Novo Inhibitor Formation
Description	The applied criteria of clinical relevance for de novo inhibitor formation was defined as normal Factor VIII dosage was ineffective to control a bleeding, control of bleeding episodes required increasing Factor VIII dosage, change of concentrate type (administration of activated Prothrombin-Complex Concentrate [aPCC] or recombinant Factor VII [rFVII ]) was needed to stop a bleeding, or change of therapy strategy (intensive prophylaxis or Immune Tolerance Induction [ITI]) was required.
Time Frame	Baseline up to a mean duration of 54 months

Outcome Measure Data

Analysis Population Description

Safety population includes all subjects with a baseline visit.

Arm/Group Title	ReFacto (Moroctocog Alfa)
Arm/Group Description	B-domain deleted, recombinant factor VIII (BDDrFVIII) for participants with Hemophilia A in usual health care settings.
Measure Participants	288
Number [participants]	7 2.4%

6. Secondary Outcome

Title	Mean Annual ReFacto Consumption Per Patient Year
Description	ReFacto administered as International Units (IU) according to the physician's decision following the drug's summary of product characteristics (SPC) and according to usual care principles.
Time Frame	Baseline up to a mean duration of 54 months

Outcome Measure Data

Analysis Population Description

Total population for efficacy analysis included all participants with submitted diary cards and severe haemophilia.

Arm/Group Title	ReFacto (Moroctocog Alfa)
Arm/Group Description	B-domain deleted, recombinant factor VIII (BDDrFVIII) for participants with Hemophilia A in usual health care settings.
Measure Participants	192
Mean (Standard Deviation) [International units per year]	204509 (221723)

7. Secondary Outcome

Title	Number of Participants for Physicians' Assessment of Satisfaction With Treatment Success
Description	Subjective assessment by the physician to evaluate treatment success (i.e., control of bleeding, Factor VIII consumption, treatment efficacy and tolerance, handling of preparation, and days missing from work or school). Physician rated assessment could be categorized as Very satisfied, Satisfied, Unsatisfied, or Very unsatisfied; no criteria was pre-specified for the assessment categories in this observational study.
Time Frame	Baseline up to a mean duration of 54 months

Outcome Measure Data

Analysis Population Description

Safety population includes all subjects with a baseline visit. N=participants with evaluable data; last measurement available.

Arm/Group Title	ReFacto (Moroctocog Alfa)
Arm/Group Description	B-domain deleted, recombinant factor VIII (BDDrFVIII) for participants with Hemophilia A in usual health care settings.
Measure Participants	169
Very satisfied	92 31.9%
Satisfied	73 25.3%
Unsatisfied	3 1%
Very unsatisfied	1 0.3%

8. Secondary Outcome

Title	Number of Participants for Physicians' Assessment of Efficacy
Description	Subjective assessment by the physician to evaluate control of bleeding. Physician rated assessment could be categorized as Very good, Good, Moderate, or Poor; no criteria was pre-specified for the assessment categories in this observational study.
Time Frame	Baseline up to a mean duration of 54 months

Outcome Measure Data

Analysis Population Description

Safety population includes all subjects with a baseline visit. N=participants with evaluable data; last measurement available.

Arm/Group Title	ReFacto (Moroctocog Alfa)
Arm/Group Description	B-domain deleted, recombinant factor VIII (BDDrFVIII) for participants with Hemophilia A in usual health care settings.
Measure Participants	269
Very good	111 38.5%
Good	111 38.5%
Moderate	38 13.2%
Poor	9 3.1%

9. Secondary Outcome

Title	Number of Participants for Patients' Assessment of Efficacy
Description	Subjective assessment by the participant to evaluate control of bleeding. Patient rated assessment could be categorized as Very good, Good, Moderate, Poor, or No specification; no criteria was pre-specified for the assessment categories in this observational study.
Time Frame	Baseline up to a mean duration of 54 months

Outcome Measure Data

Analysis Population Description

Safety population includes all subjects with a baseline visit. N=participants with evaluable data; last measurement available.

Arm/Group Title	ReFacto (Moroctocog Alfa)
Arm/Group Description	B-domain deleted, recombinant factor VIII (BDDrFVIII) for participants with Hemophilia A in usual health care settings.
Measure Participants	269
Very good	103 35.8%
Good	116 40.3%
Moderate	35 12.2%
Poor	11 3.8%
No specification	4 1.4%

10. Secondary Outcome

Title	Number of Participants for Physicians' Assessment of Tolerance
Description	Subjective assessment by the physician to evaluate the participants' tolerance of treatment with ReFacto (i.e., dose, administration method, or adverse effects). Physician rated assessment could be categorized as Very good, Good, Moderate, or Poor; no criteria was pre-specified for the assessment categories in this observational study.
Time Frame	Baseline up to a mean duration of 54 months

Outcome Measure Data

Analysis Population Description

Safety population includes all subjects with a baseline visit. N=participants with evaluable data; last measurement available.

Arm/Group Title	ReFacto (Moroctocog Alfa)
Arm/Group Description	B-domain deleted, recombinant factor VIII (BDDrFVIII) for participants with Hemophilia A in usual health care settings.
Measure Participants	269
Very good	130 45.1%
Good	137 47.6%
Moderate	2 0.7%

11. Secondary Outcome

Title	Number of Participants for Patients' Assessment of Tolerance
Description	Subjective assessment by the participant to evaluate tolerance of treatment with ReFacto (i.e., dose, administration method, or adverse effects). Patient rated assessment could be categorized as Very good, Good, Moderate, Poor, or No specification; no criteria was pre-specified for the assessment categories in this observational study.
Time Frame	Baseline up to a mean duration of 54 months

Outcome Measure Data

Analysis Population Description

Safety population includes all subjects with a baseline visit. N=participants with evaluable data; last measurement available.

Arm/Group Title	ReFacto (Moroctocog Alfa)
Arm/Group Description	B-domain deleted, recombinant factor VIII (BDDrFVIII) for participants with Hemophilia A in usual health care settings.
Measure Participants	269
Very good	131 45.5%
Good	132 45.8%
Moderate	1 0.3%
Poor	1 0.3%
No specification	4 1.4%

12. Secondary Outcome

Title	Number of Participants for Physicians' Assessment of Handling of ReFacto
Description	Subjective assessment by the physician to evaluate the participants' handling (preparation and administration) of ReFacto. Physician rated assessment could be categorized as Very good, Good, Moderate, or Poor; no criteria was pre-specified for the assessment categories in this observational study.
Time Frame	Baseline up to a mean duration of 54 months

Outcome Measure Data

Analysis Population Description

Safety population includes all subjects with a baseline visit. N=participants with evaluable data; last measurement available.

Arm/Group Title	ReFacto (Moroctocog Alfa)
Arm/Group Description	B-domain deleted, recombinant factor VIII (BDDrFVIII) for participants with Hemophilia A in usual health care settings.
Measure Participants	269
Very good	109 37.8%
Good	154 53.5%
Moderate	6 2.1%

13. Secondary Outcome

Title	Number of Participants for Patients' Assessment of Handling of ReFacto
Description	Subjective assessment by the participant on handling (preparation and administration) of ReFacto. Patient rated assessment could be categorized as Very good, Good, Moderate, Poor, or No specification; no criteria was pre-specified for the assessment categories in this observational study.
Time Frame	Baseline up to a mean duration of 54 months

Outcome Measure Data

Analysis Population Description

Safety population includes all subjects with a baseline visit. N=participants with evaluable data; last measurement available.

Arm/Group Title	ReFacto (Moroctocog Alfa)
Arm/Group Description	B-domain deleted, recombinant factor VIII (BDDrFVIII) for participants with Hemophilia A in usual health care settings.
Measure Participants	269
Very good	99 34.4%
Good	154 53.5%
Moderate	11 3.8%
Poor	1 0.3%
No specification	4 1.4%

14. Secondary Outcome

Title	Number of Participants for Days of Sick Leave Per Month
Description	Days of sick leave (missing work or school) per month categorized as No days of absence, Number of days of absence, Long-term inability to work or study, Not employed or at school, or No specification.
Time Frame	Baseline up to a mean duration of 54 months

Outcome Measure Data

Analysis Population Description

Safety population includes all subjects with a baseline visit. N=participants with evaluable data; last measurement available.

Arm/Group Title	ReFacto (Moroctocog Alfa)
Arm/Group Description	B-domain deleted, recombinant factor VIII (BDDrFVIII) for participants with Hemophilia A in usual health care settings.
Measure Participants	169
No days of absence	87 30.2%
<6 days of absence	32 11.1%
6 to 10 days of absence	4 1.4%
>10 days of absence	8 2.8%
Long-term inability to work or study	0 0%
Not employed or at school	36 12.5%
No specification	2 0.7%

Adverse Events

Time Frame	Baseline up to a mean duration of 54 months
Adverse Event Reporting Description	The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Arm/Group Title	ReFacto (Moroctocog Alfa)
Arm/Group Description	B-domain deleted, recombinant factor VIII (BDDrFVIII) for participants with Hemophilia A in usual health care settings.
All Cause Mortality
	ReFacto (Moroctocog Alfa)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	ReFacto (Moroctocog Alfa)
	Affected / at Risk (%)	# Events
Total	141/288 (49%)
Blood and lymphatic system disorders
Haemolysis	1/288 (0.3%)
Cardiac disorders
Acute coronary syndrome	1/288 (0.3%)
Acute myocardial infarction	1/288 (0.3%)
Angina pectoris	2/288 (0.7%)
Cardiomyopathy	1/288 (0.3%)
Myocardial infarction	1/288 (0.3%)
Congenital, familial and genetic disorders
Phimosis	2/288 (0.7%)
Ear and labyrinth disorders
Conductive deafness	1/288 (0.3%)
Middle ear effusion	1/288 (0.3%)
Gastrointestinal disorders
Acute abdomen	1/288 (0.3%)
Dental caries	1/288 (0.3%)
Enteritis	1/288 (0.3%)
Gastric ulcer haemorrhage	1/288 (0.3%)
Gastrointestinal haemorrhage	2/288 (0.7%)
Gingival bleeding	1/288 (0.3%)
Haematemesis	1/288 (0.3%)
Ileus	1/288 (0.3%)
Inguinal hernia	2/288 (0.7%)
Intestinal infarction	1/288 (0.3%)
Lip haemorrhage	1/288 (0.3%)
Melaena	1/288 (0.3%)
Mouth haemorrhage	1/288 (0.3%)
Oesophageal varices haemorrhage	2/288 (0.7%)
Retroperitoneal haematoma	1/288 (0.3%)
Small intestinal haemorrhage	1/288 (0.3%)
Tooth impacted	1/288 (0.3%)
General disorders
Chills	1/288 (0.3%)
Concomitant disease progression	1/288 (0.3%)
Condition aggravated	6/288 (2.1%)
Death	1/288 (0.3%)
Developmental delay	1/288 (0.3%)
Drug ineffective	42/288 (14.6%)
Impaired healing	1/288 (0.3%)
Local swelling	1/288 (0.3%)
Medical device complication	1/288 (0.3%)
Pyrexia	1/288 (0.3%)
Thrombosis in device	1/288 (0.3%)
Unevaluable event	1/288 (0.3%)
Hepatobiliary disorders
Cholelithiasis	1/288 (0.3%)
Gallbladder polyp	1/288 (0.3%)
Hepatic cirrhosis	1/288 (0.3%)
Hepatic failure	3/288 (1%)
Infections and infestations
Acquired immunodeficiency syndrome	1/288 (0.3%)
Anogenital warts	1/288 (0.3%)
Appendicitis	3/288 (1%)
Bronchitis	1/288 (0.3%)
Bronchopneumonia	1/288 (0.3%)
Cerebral toxoplasmosis	1/288 (0.3%)
Device related infection	4/288 (1.4%)
Gastroenteritis	2/288 (0.7%)
Implant site infection	1/288 (0.3%)
Klebsiella sepsis	1/288 (0.3%)
Meningitis	1/288 (0.3%)
Osteomyelitis	1/288 (0.3%)
Paronychia	1/288 (0.3%)
Pilonidal cyst	1/288 (0.3%)
Pneumocystis jiroveci pneumonia	1/288 (0.3%)
Pneumonia	1/288 (0.3%)
Pneumonia staphylococcal	1/288 (0.3%)
Salmonellosis	1/288 (0.3%)
Staphylococcal infection	1/288 (0.3%)
Tooth abscess	1/288 (0.3%)
Viral upper respiratory tract infection	1/288 (0.3%)
Injury, poisoning and procedural complications
Accidental overdose	1/288 (0.3%)
Concussion	1/288 (0.3%)
Contusion	1/288 (0.3%)
Fall	5/288 (1.7%)
Femoral neck fracture	1/288 (0.3%)
Femur fracture	1/288 (0.3%)
Foot fracture	2/288 (0.7%)
Forearm fracture	1/288 (0.3%)
Hepatic rupture	1/288 (0.3%)
Humerus fracture	1/288 (0.3%)
Injury	2/288 (0.7%)
Muscle strain	1/288 (0.3%)
Post procedural haemorrhage	2/288 (0.7%)
Radius fracture	2/288 (0.7%)
Skull fractured base	1/288 (0.3%)
Subdural haematoma	1/288 (0.3%)
Thermal burn	1/288 (0.3%)
Traumatic brain injury	1/288 (0.3%)
Wound	1/288 (0.3%)
Investigations
Alanine aminotransferase increased	1/288 (0.3%)
Anti factor VIII antibody positive	1/288 (0.3%)
Anti factor VIII antibody test	22/288 (7.6%)
Antiphospholipid antibodies	1/288 (0.3%)
Aspartate aminotransferase increased	1/288 (0.3%)
Biopsy testes	1/288 (0.3%)
Blood urine present	1/288 (0.3%)
Catheterisation cardiac	1/288 (0.3%)
Coagulation factor VIII level decreased	1/288 (0.3%)
Coagulation factor inhibitor assay	1/288 (0.3%)
Drug specific antibody present	1/288 (0.3%)
Free haemoglobin present	1/288 (0.3%)
Gamma-glutamyltransferase increased	1/288 (0.3%)
Investigation	1/288 (0.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/288 (0.3%)
Arthritis	1/288 (0.3%)
Fistula	1/288 (0.3%)
Flank pain	1/288 (0.3%)
Haemarthrosis	8/288 (2.8%)
Haemophilic arthropathy	4/288 (1.4%)
Muscle haemorrhage	1/288 (0.3%)
Synovitis	1/288 (0.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Central nervous system lymphoma	1/288 (0.3%)
Hepatic neoplasm malignant	1/288 (0.3%)
Nervous system disorders
Cerebral haemorrhage	5/288 (1.7%)
Convulsion	1/288 (0.3%)
Cubital tunnel syndrome	1/288 (0.3%)
Dyspraxia	1/288 (0.3%)
Febrile convulsion	1/288 (0.3%)
Peripheral sensory neuropathy	1/288 (0.3%)
Psychiatric disorders
Antisocial behaviour	1/288 (0.3%)
Attention deficit/hyperactivity disorder	1/288 (0.3%)
Renal and urinary disorders
Calculus ureteric	1/288 (0.3%)
Enuresis	1/288 (0.3%)
Haematuria	4/288 (1.4%)
Nephrolithiasis	1/288 (0.3%)
Renal colic	1/288 (0.3%)
Renal haemorrhage	1/288 (0.3%)
Reproductive system and breast disorders
Testicular haemorrhage	1/288 (0.3%)
Respiratory, thoracic and mediastinal disorders
Adenoidal hypertrophy	1/288 (0.3%)
Asthma	1/288 (0.3%)
Skin and subcutaneous tissue disorders
Henoch-Schonlein purpura	1/288 (0.3%)
Surgical and medical procedures
Adenotonsillectomy	1/288 (0.3%)
Arthrodesis	1/288 (0.3%)
Bone operation	1/288 (0.3%)
Central venous catheter removal	4/288 (1.4%)
Dental care	1/288 (0.3%)
Ear tube insertion	1/288 (0.3%)
Hip arthroplasty	1/288 (0.3%)
Joint arthroplasty	2/288 (0.7%)
Joint surgery	1/288 (0.3%)
Knee arthroplasty	2/288 (0.7%)
Ossiculoplasty	1/288 (0.3%)
Skin neoplasm excision	1/288 (0.3%)
Surgery	2/288 (0.7%)
Thyroidectomy	1/288 (0.3%)
Tooth extraction	1/288 (0.3%)
Vascular operation	1/288 (0.3%)
Wisdom teeth removal	1/288 (0.3%)
Vascular disorders
Circulatory collapse	1/288 (0.3%)
Haematoma	7/288 (2.4%)
Haemorrhage	9/288 (3.1%)
Vein disorder	1/288 (0.3%)
Other (Not Including Serious) Adverse Events
	ReFacto (Moroctocog Alfa)
	Affected / at Risk (%)	# Events
Total	118/288 (41%)
Blood and lymphatic system disorders
Iron deficiency anaemia	1/288 (0.3%)
Spontaneous haematoma	1/288 (0.3%)
Thrombocytopenia	2/288 (0.7%)
Cardiac disorders
Palpitations	1/288 (0.3%)
Congenital, familial and genetic disorders
Phimosis	1/288 (0.3%)
Ear and labyrinth disorders
Tinnitus	2/288 (0.7%)
Endocrine disorders
Hypothyroidism	1/288 (0.3%)
Eye disorders
Conjunctivitis	1/288 (0.3%)
Eye haemorrhage	3/288 (1%)
Vision blurred	1/288 (0.3%)
Visual impairment	1/288 (0.3%)
Gastrointestinal disorders
Abdominal discomfort	1/288 (0.3%)
Abdominal distension	1/288 (0.3%)
Abdominal pain	2/288 (0.7%)
Abdominal pain upper	2/288 (0.7%)
Cheilosis	2/288 (0.7%)
Dental caries	1/288 (0.3%)
Dyspepsia	1/288 (0.3%)
Gastrointestinal disorder	1/288 (0.3%)
Gastrointestinal haemorrhage	2/288 (0.7%)
Gastrointestinal pain	1/288 (0.3%)
Gingival bleeding	1/288 (0.3%)
Haematemesis	1/288 (0.3%)
Haematochezia	1/288 (0.3%)
Inflammatory bowel disease	1/288 (0.3%)
Lip haemorrhage	1/288 (0.3%)
Mouth haemorrhage	1/288 (0.3%)
Nausea	2/288 (0.7%)
Stomatitis	1/288 (0.3%)
Tooth loss	1/288 (0.3%)
Tooth socket haemorrhage	1/288 (0.3%)
Vomiting	2/288 (0.7%)
General disorders
Discomfort	1/288 (0.3%)
Drug ineffective	2/288 (0.7%)
General physical health deterioration	1/288 (0.3%)
Inflammation	2/288 (0.7%)
Influenza like illness	3/288 (1%)
Oedema	1/288 (0.3%)
Oedema peripheral	2/288 (0.7%)
Pain	3/288 (1%)
Pyrexia	6/288 (2.1%)
Unevaluable event	2/288 (0.7%)
Unevaluable event	4/288 (1.4%)
Hepatobiliary disorders
Hepatic cirrhosis	2/288 (0.7%)
Immune system disorders
Drug hypersensitivity	1/288 (0.3%)
Seasonal allergy	3/288 (1%)
Infections and infestations
Acquired immunodeficiency syndrome	1/288 (0.3%)
Acute tonsillitis	1/288 (0.3%)
Bronchitis	2/288 (0.7%)
Device related infection	1/288 (0.3%)
Ear infection	1/288 (0.3%)
Gastrointestinal infection	1/288 (0.3%)
HIV infection	1/288 (0.3%)
Hepatitis C	1/288 (0.3%)
Herpes zoster	1/288 (0.3%)
Infection	2/288 (0.7%)
Influenza	2/288 (0.7%)
Localised infection	1/288 (0.3%)
Nasopharyngitis	1/288 (0.3%)
Otitis externa	1/288 (0.3%)
Otitis media viral	1/288 (0.3%)
Parotitis	1/288 (0.3%)
Pneumonia	1/288 (0.3%)
Rhinitis	2/288 (0.7%)
Sinusitis	1/288 (0.3%)
Streptococcal infection	1/288 (0.3%)
Upper respiratory tract infection	1/288 (0.3%)
Urinary tract infection	2/288 (0.7%)
Injury, poisoning and procedural complications
Accident at work	1/288 (0.3%)
Bite	1/288 (0.3%)
Contusion	2/288 (0.7%)
Electric shock	1/288 (0.3%)
Excoriation	1/288 (0.3%)
Face injury	3/288 (1%)
Fall	18/288 (6.3%)
Foot fracture	1/288 (0.3%)
Genital injury	1/288 (0.3%)
Hand fracture	1/288 (0.3%)
Head injury	5/288 (1.7%)
Injury	5/288 (1.7%)
Joint injury	6/288 (2.1%)
Joint sprain	2/288 (0.7%)
Limb crushing injury	3/288 (1%)
Limb injury	8/288 (2.8%)
Mouth injury	2/288 (0.7%)
Muscle rupture	1/288 (0.3%)
Open wound	1/288 (0.3%)
Post procedural haematoma	1/288 (0.3%)
Post procedural haemorrhage	1/288 (0.3%)
Skin injury	1/288 (0.3%)
Tendon rupture	1/288 (0.3%)
Tibia fracture	1/288 (0.3%)
Traumatic brain injury	1/288 (0.3%)
Traumatic haematoma	5/288 (1.7%)
Traumatic haemorrhage	4/288 (1.4%)
Wound	3/288 (1%)
Investigations
Arthroscopy	1/288 (0.3%)
Biopsy stomach	1/288 (0.3%)
Blood lactate dehydrogenase increased	2/288 (0.7%)
Blood urine present	1/288 (0.3%)
Coagulation factor VIII level decreased	10/288 (3.5%)
Endoscopy upper gastrointestinal tract	1/288 (0.3%)
Free haemoglobin present	1/288 (0.3%)
Liver function test abnormal	1/288 (0.3%)
Urine analysis abnormal	1/288 (0.3%)
Weight decreased	1/288 (0.3%)
Metabolism and nutrition disorders
Gout	1/288 (0.3%)
Obesity	1/288 (0.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	5/288 (1.7%)
Exostosis	1/288 (0.3%)
Flank pain	1/288 (0.3%)
Haemarthrosis	37/288 (12.8%)
Haemophilic arthropathy	1/288 (0.3%)
Joint swelling	3/288 (1%)
Lordosis	1/288 (0.3%)
Muscle haemorrhage	8/288 (2.8%)
Muscle spasms	1/288 (0.3%)
Musculoskeletal discomfort	1/288 (0.3%)
Musculoskeletal pain	1/288 (0.3%)
Pain in extremity	5/288 (1.7%)
Pain in jaw	1/288 (0.3%)
Soft tissue haemorrhage	3/288 (1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant melanoma	1/288 (0.3%)
Melanocytic naevus	1/288 (0.3%)
Nervous system disorders
Disturbance in attention	2/288 (0.7%)
Dizziness	2/288 (0.7%)
Facial nerve disorder	1/288 (0.3%)
Headache	2/288 (0.7%)
Mental impairment	1/288 (0.3%)
Tongue biting	2/288 (0.7%)
Psychiatric disorders
Affect lability	1/288 (0.3%)
Apathy	1/288 (0.3%)
Insomnia	1/288 (0.3%)
Restlessness	1/288 (0.3%)
Violence-related symptom	1/288 (0.3%)
Renal and urinary disorders
Haematuria	4/288 (1.4%)
Nephrolithiasis	2/288 (0.7%)
Renal colic	1/288 (0.3%)
Renal haemorrhage	3/288 (1%)
Renal pain	1/288 (0.3%)
Urinary tract obstruction	1/288 (0.3%)
Reproductive system and breast disorders
Breast haematoma	1/288 (0.3%)
Gynaecomastia	1/288 (0.3%)
Testicular pain	1/288 (0.3%)
Respiratory, thoracic and mediastinal disorders
Cough	2/288 (0.7%)
Epistaxis	6/288 (2.1%)
Rhinitis allergic	1/288 (0.3%)
Sleep apnoea syndrome	1/288 (0.3%)
Tonsillar inflammation	1/288 (0.3%)
Skin and subcutaneous tissue disorders
Dermal cyst	1/288 (0.3%)
Ecchymosis	2/288 (0.7%)
Haemorrhage subcutaneous	1/288 (0.3%)
Hyperhidrosis	1/288 (0.3%)
Rash	1/288 (0.3%)
Skin chapped	2/288 (0.7%)
Skin lesion	1/288 (0.3%)
Skin ulcer	2/288 (0.7%)
Subcutaneous nodule	1/288 (0.3%)
Urticaria	1/288 (0.3%)
Surgical and medical procedures
Adenotonsillectomy	1/288 (0.3%)
Bursa removal	1/288 (0.3%)
Catheterisation venous	1/288 (0.3%)
Central venous catheter removal	2/288 (0.7%)
Central venous catheterisation	4/288 (1.4%)
Dental care	1/288 (0.3%)
Hospitalisation	3/288 (1%)
Joint injection	1/288 (0.3%)
Medical device implantation	1/288 (0.3%)
Medical device removal	1/288 (0.3%)
Penile operation	1/288 (0.3%)
Plastic surgery	1/288 (0.3%)
Radiotherapy to joint	2/288 (0.7%)
Suture insertion	1/288 (0.3%)
Suture removal	1/288 (0.3%)
Synovectomy	2/288 (0.7%)
Tonsillectomy	1/288 (0.3%)
Tooth extraction	5/288 (1.7%)
Wisdom teeth removal	1/288 (0.3%)
Vascular disorders
Haematoma	9/288 (3.1%)
Haemorrhage	22/288 (7.6%)
Lymphostasis	1/288 (0.3%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

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

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.