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Trial record 11 of 13 for:    bleeding episodes | ( Map: Greece )

Study Evaluating Safety Of Patients Switching To ReFacto AF In Usual Care Settings

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ClinicalTrials.gov Identifier: NCT00884390
Recruitment Status : Terminated (See termination reason in detailed description.)
First Posted : April 20, 2009
Results First Posted : September 1, 2014
Last Update Posted : September 1, 2014
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Hemophilia A
Interventions Drug: moroctocog alfa (AF-CC) (ReFacto AF)
Procedure: Laboratory tests
Enrollment 208
Recruitment Details Two hundred and eight (208) participants were enrolled into the study (146 participants into the ReFacto Switch group [Cohort 1: participants who switched from ReFacto to ReFacto AF] and 62 participants into the Other Switch group [Cohort 2: participants who switched from other Factor VIII (FVIII) products other than ReFacto to ReFacto AF]).
Pre-assignment Details  
Arm/Group Title ReFacto Switch Other Switch
Hide Arm/Group Description Participants who switched from ReFacto to ReFacto AF Participants who switched from other FVIII products other than ReFacto to ReFacto AF
Period Title: Overall Study
Started 146 62
Completed 123 54
Not Completed 23 8
Reason Not Completed
Adverse Event             0             1
Lost to Follow-up             0             1
Physician Decision             2             1
Protocol Violation             4             1
Withdrawal by Subject             4             1
Discontinuation of Study by Sponsor             2             2
Not specified             11             1
Arm/Group Title ReFacto Switch Other Switch Total
Hide Arm/Group Description Participants who switched from ReFacto to ReFacto AF Participants who switched from other FVIII products other than ReFacto to ReFacto AF Total of all reporting groups
Overall Number of Baseline Participants 146 62 208
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 146 participants 62 participants 208 participants
12-17 years 33 9 42
18-65 years 113 53 166
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 146 participants 62 participants 208 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
Male
146
 100.0%
62
 100.0%
208
 100.0%
1.Primary Outcome
Title Number of Participants With Clinically Significant Factor VIII Inhibitor Development
Hide Description Number of participants with clinically significant FVIII inhibitor development after switching from ReFacto to moroctocog alfa (AF-CC). Clinically significant inhibitors are defined as a central laboratory confirmed positive inhibitor (≥ 0.6 Bethesda unit (BU) using the Nijmegen modification of the Bethesda assay present at 2 consecutive blood draws within a 6-week interval) and within 28 days before the initial or within 28 days following the second positive FVIII inhibitor sample collection one of the following: the need for the participant to administer alternative hemostatic products in order to achieve sufficient efficacy, or ≥2 adverse event reports of decreased drug effect (or other adverse event indicating a decrease in the efficacy of the test article). The blood sample collection for these results must also be between the date of first dose of study medication and 28 days after the last dose of study medication.
Time Frame 100 exposure days to study medication (approx. 2 years)
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants who took at least 1 dose of ReFacto AF study drug were included in the safety and efficacy analyses.
Arm/Group Title ReFacto Switch Other Switch
Hide Arm/Group Description:
Participants who switched from ReFacto to ReFacto AF
Participants who switched from other FVIII products other than ReFacto to ReFacto AF
Overall Number of Participants Analyzed 146 62
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Number of participants
0
(0.00 to 2.49)
0
(0.00 to 5.78)
2.Secondary Outcome
Title Annualized Bleeding Rates (ABRs)
Hide Description An ABR for each participant will be calculated as the number of bleeds requiring administration of FVIII replacement product (taken from the Infusion Log Diary case report form), divided by his total therapy duration (in days), then multiplied by 365.25.
Time Frame 100 exposure days to study medication (approx. 2 years)
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants who took at least 1 dose of ReFacto AF study drug were included in the safety and efficacy analyses.
Arm/Group Title Annualized Bleed Rate
Hide Arm/Group Description:
ABR by regimen at baseline is summarized for all participants for on-demand regimen, preventive regimen and prophylaxis regimen, respectively
Overall Number of Participants Analyzed 208
Mean (Standard Deviation)
Unit of Measure: Number of bleeds
On-demand regimen (N=52) 28.35  (18.781)
Preventive regimen (N=2) 1.08  (1.528)
Primary or secondary prophylaxis regimen (N=154) 8.43  (17.362)
3.Secondary Outcome
Title Response Assessment of First On-demand Treatment of New Bleeds
Hide Description

A 4-point scale of assessment of ‘on-demand’ treatment (administration of an unscheduled bolus infusion of Refacto-AF to stop bleeding) is defined as:

  • Excellent: Definite pain relief and/or improvement in signs of bleeding starting within 8 hours after an infusion, with no additional infusion administered.
  • Good: Definite pain relief and/or improvement in signs of bleeding starting within 8 hours after an infusion, with at least one additional infusion administered for complete resolution of the bleeding episode; or, Definite pain relief and/or improvement in signs of bleeding starting after 8 hours following the infusion, with no additional infusion administered.
  • Moderate: Probable or slight improvement starting after 8 hours following the infusion, with at least one additional infusion administered for complete resolution of the bleeding episode.
  • No Response: No improvement at all between infusions or during the 24-hour interval following an infusion, or condition worsens.
Time Frame 100 exposure days to study medication (approx. 2 years)
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants who took at least 1 dose of ReFacto AF study drug were included in the safety and efficacy analyses.
Arm/Group Title First Infusion Per Bleed
Hide Arm/Group Description:
Includes the first infusion for an associated bleeding episode
Overall Number of Participants Analyzed 156
Measure Type: Number
Unit of Measure: Number of observations
Excellent 1650
Good 1031
Moderate 191
No response 26
Data Not Recorded 343
Total 3241
4.Secondary Outcome
Title Number of ReFacto AF Infusions to Treat Each New Bleed
Hide Description The Infusion Log Diary case report form (CRF) was used to determine the number of test article infusions administered to treat a bleed. This was calculated by adding the initial (on-demand) infusion to any subsequent (on-demand) infusions for the same bleed (same bleed start date/time).
Time Frame 100 exposure days to study medication (approx. 2 years)
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants who took at least 1 dose of ReFacto AF study drug were included in the safety and efficacy analyses.
Arm/Group Title All Participants With Bleeds
Hide Arm/Group Description:
Includes any infusion with an associated bleeding episode, regardless of the reason for treatment indicated on the case report form
Overall Number of Participants Analyzed 156
Mean (Standard Deviation)
Unit of Measure: Number of Infusions
Excellent 1.1  (0.66)
Good 1.4  (1.45)
Moderate 2.0  (1.63)
No response 2.5  (2.60)
Data Not Recorded 1.3  (1.55)
5.Secondary Outcome
Title Number of Bleeding Episodes Occurring ≤48 Hours After a Prophylaxis Infusion
Hide Description First, the bleed start time from the Infusion Log Diary CRF was used to determine the number of breakthrough bleeds that occurred ≤48 hours after an infusion marked as “Prophylaxis” (which had no associated bleed). If there was more than 1 bleed location (ie, ankle and joint) with identical bleed start date and time, it was treated as 1 bleed occurrence. If a response was given, or if a bleed time was given, but “On Demand” was not listed as “treatment type”, it was still counted as an on-demand bleed for analyses/summaries. Bleeding episodes were not categorized as spontaneous (atraumatic) or traumatic.
Time Frame 100 exposure days to study medication (approx. 2 years)
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants who took at least 1 dose of ReFacto AF study drug were included in the safety and efficacy analyses.
Arm/Group Title Participants Who Received at Least One Prophylactic Infusion
Hide Arm/Group Description:
Participants who had at least one prophylaxis dose, and at least one bleed.
Overall Number of Participants Analyzed 108
Measure Type: Number
Unit of Measure: bleeds
96
6.Secondary Outcome
Title Number of Participants With Breakthrough Bleeds
Hide Description The number of participants with any breakthrough bleed was reported.
Time Frame 100 exposure days to study medication (approx. 2 years)
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants who took at least 1 dose of ReFacto AF study drug were included in the safety and efficacy analyses.
Arm/Group Title Participants Who Received at Least One Prophylactic Infusion
Hide Arm/Group Description:
Participants who had at least one prophylaxis dose, and at least one bleed.
Overall Number of Participants Analyzed 108
Measure Type: Number
Unit of Measure: participants
33
7.Secondary Outcome
Title Total Factor Consumption (TFC) Following a Non-prophylaxis Regimen at Baseline for All Participants
Hide Description The total amount (in International Units [IU]) infused for each test article infusion recorded in the Infusion Log Diary CRF was summed to calculate the TFC for each participant.
Time Frame 100 exposure days to study medication (approx. 2 years)
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants who took at least 1 dose of ReFacto AF study drug were included in the safety and efficacy analyses.
Arm/Group Title All Participants
Hide Arm/Group Description:
All enrolled participants following a non-prophylaxis regimen at baseline.
Overall Number of Participants Analyzed 54
Mean (Standard Deviation)
Unit of Measure: International Units (IU)
On demand (n=50) 115451.5  (67186.92)
Preventive (n=43) 35156.8  (40690.91)
Prophylaxis (n=19) 73001.9  (66969.64)
Not specified (n=54) 39268.3  (65013.77)
Total (n=54) 199848.9  (79308.82)
8.Secondary Outcome
Title TFC Following a Prophylaxis Regimen at Baseline for All Participants
Hide Description The total amount (in IU) infused for each test article infusion recorded in the Infusion Log Diary CRF was summed to calculate the TFC for each participant.
Time Frame 100 exposure days to study medication (approx. 2 years)
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants who took at least 1 dose of ReFacto AF study drug were included in the safety and efficacy analyses.
Arm/Group Title All Participants
Hide Arm/Group Description:
All enrolled participants following a non-prophylaxis regimen at baseline.
Overall Number of Participants Analyzed 154
Mean (Standard Deviation)
Unit of Measure: IU
On Demand (n=98) 26063.4  (32876.96)
Preventive (n=65) 22498.8  (29987.52)
Prophylaxis (n=143) 165124.6  (88373.55)
Not specified (n=154) 43812.8  (67588.23)
Total (n=154) 223224.8  (86493.58)
9.Secondary Outcome
Title Average Infusion Dose
Hide Description The average infusion dose for each participant was calculated as his total factor consumption (in IU) divided by the number of infusions administered. Summary statistics were reported for both of these variables separately for those participants classified at baseline as following an on-demand regimen, and for those on a primary or secondary prophylaxis regimen.
Time Frame 100 exposure days to study medication (approx. 2 years)
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants who took at least 1 dose of ReFacto AF study drug were included in the safety and efficacy analyses.
Arm/Group Title Participants Following a Non-prophylaxis Regimen at Baseline Participants Following a Prophylaxis Regimen at Baseline
Hide Arm/Group Description:
All enrolled participants following an on-demand or preventive regimen at baseline
All enrolled participants following a prophylaxis regimen at baseline
Overall Number of Participants Analyzed 54 154
Mean (Standard Deviation)
Unit of Measure: IU
2326.8  (691.31) 2290.3  (701.36)
10.Secondary Outcome
Title Incidence of Less-than-expected-therapeutic Effect (LETE) in the On-demand Setting
Hide Description The calculation of incidence of on-demand LETE used the number of bleeds identified as, or with a result of, LETE as the numerator (from the On Demand LETE CRF), and the denominator was the number of bleeding episodes treated in an on-demand setting. This denominator could include new bleeding episodes in prophylaxis participants breakthrough bleeds), and if subsequent on-demand doses for such a bleed met the on-demand LETE criteria, then an on-demand LETE was reported.
Time Frame 100 exposure days to study medication (approx. 2 years)
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants who took at least 1 dose of ReFacto AF study drug were included in the safety and efficacy analyses.
Arm/Group Title All Participants With at Least One Bleed
Hide Arm/Group Description:
All enrolled participants with at least one bleed.
Overall Number of Participants Analyzed 208
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of bleeds LETE
0.06
(0.01 to 0.22)
11.Secondary Outcome
Title Incidence of Less-than-expected-therapeutic Effect (LETE) in the Prophylaxis Setting
Hide Description The calculation of incidence of prophylaxis LETE used the number of bleeds identified as, or with a result of, LETE as the numerator (from the Prophylactic LETE CRF), and the denominator was the number of routine prophylaxis infusions. Each infusion was classified in the infusion log (“Prophylaxis/ On Demand/ Preventive”), and participants were instructed to select “On Demand” if the infusion was to treat a bleed, even if the participant typically followed a prophylaxis regimen. Only the infusions classified as “Prophylaxis” were counted in this denominator.
Time Frame 100 exposure days to study medication (approx. 2 years)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title All Participants With at Least One Prophylaxis Infusion
Hide Arm/Group Description:
All enrolled participants with at least one prophylaxis infusion
Overall Number of Participants Analyzed 208
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of bleeding episodes
0.19
(0.12 to 0.28)
Time Frame Duration of participation in study
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 All Participants
Hide Arm/Group Description The primary safety analysis was performed on all subjects who received at least 1 dose of ReFacto AF.
All-Cause Mortality
All Participants
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
All Participants
Affected / at Risk (%) # Events
Total   20/208 (9.62%)    
Blood and lymphatic system disorders   
Factor VIII inhibition  1  5/208 (2.40%)  5
Eye disorders   
Photophobia  1  1/208 (0.48%)  1
Visual impairment  1  1/208 (0.48%)  1
Gastrointestinal disorders   
Acute abdomen  1  1/208 (0.48%)  1
Dyspepsia  1  1/208 (0.48%)  1
Haematemesis  1  1/208 (0.48%)  1
Intestinal haematoma  1  1/208 (0.48%)  1
Intestinal obstruction  1  1/208 (0.48%)  1
Mallory-Weiss syndrome  1  1/208 (0.48%)  1
General disorders   
Chills  1  1/208 (0.48%)  1
Pain  1  1/208 (0.48%)  1
Infections and infestations   
Acute tonsillitis  1  1/208 (0.48%)  1
Post procedural infection  1  1/208 (0.48%)  1
Septic arthritis streptococcal  1  1/208 (0.48%)  1
Injury, poisoning and procedural complications   
Alcohol poisoning  1  1/208 (0.48%)  1
Tooth fracture  1  1/208 (0.48%)  1
Investigations   
Anti factor VIII antibody positive  1  1/208 (0.48%)  1
Musculoskeletal and connective tissue disorders   
Muscle haemorrhage  1  1/208 (0.48%)  1
Musculoskeletal stiffness  1  1/208 (0.48%)  2
Pain in extremity  1  1/208 (0.48%)  1
Nervous system disorders   
Headache  1  1/208 (0.48%)  1
Syncope  1  1/208 (0.48%)  1
Respiratory, thoracic and mediastinal disorders   
Epistaxis  1  1/208 (0.48%)  1
Oropharyngeal pain  1  1/208 (0.48%)  1
Skin and subcutaneous tissue disorders   
Hyperhidrosis  1  1/208 (0.48%)  1
Vascular disorders   
Hypertension  1  1/208 (0.48%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
All Participants
Affected / at Risk (%) # Events
Total   90/208 (43.27%)    
Infections and infestations   
Nasopharyngitis  1  32/208 (15.38%)  44
Influenza  1  13/208 (6.25%)  18
Injury, poisoning and procedural complications   
Limb injury  1  15/208 (7.21%)  25
Musculoskeletal and connective tissue disorders   
Arthralgia  1  26/208 (12.50%)  69
Haemarthrosis  1  24/208 (11.54%)  86
Nervous system disorders   
Headache  1  21/208 (10.10%)  47
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
The study was terminated early by agreement with the EMA before full recruitment was attained, but this is not considered to affect the overall results and the ability of the study to address its objectives.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
Phone: 1-800-718-1021
EMail: ClinicalTrials.gov_Inquiries@pfizer.com
Layout table for additonal information
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00884390     History of Changes
Other Study ID Numbers: 3082B2-4432
First Submitted: April 16, 2009
First Posted: April 20, 2009
Results First Submitted: March 20, 2014
Results First Posted: September 1, 2014
Last Update Posted: September 1, 2014