Observational Registry of NovoSeven® Used as On-demand Treatment of Bleeds in Patients With Haemophilia A and B With Inhibitors

Study Overview
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Brief Summary
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This study was conducted in Africa, Europe, the Middle-East and South America. The primary objective of this registry was to observe the use of single dose and multi-dose use of activated recombinant human factor VII and to compare short-term outcomes, including effectiveness, safety, quality of life and treatment satisfaction with the approved treatments.

Official Title
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A Prospective Observational Registry on the Use of NovoSeven® (Activated Recombinant Human Factor VIIa) for on Demand Treatment of Mild to Moderate Bleeds in Haemophilia A and B Patients With Inhibitors

Conditions
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Congenital Bleeding Disorder, Haemophilia A With Inhibitors, Haemophilia B With Inhibitors

Intervention / Treatment
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* Drug: eptacog alfa (activated)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with haemophilia A or B with inhibitors Experience mild to moderate spontaneous bleeds which require on-demand treatment and who are currently prescribed activated recombinant human factor VII Be able and willing to provide informed consent (or proxy consent by caregiver, if applicable), as required by local research ethics committee, governmental or regulatory authorities Be willing to provide information on at least one alternate contact person in the event that the patient be somehow lost-to-follow-up over the course of registry participation (not applicable if patient is withdrawn) Exclusion Criteria: Known hypersensitivity to the active substance or the excipients in the formulation of activated recombinant human factor VII, or to mouse, hamster or bovine protein
Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| activated recombinant human factor VII<br>Male patients above 2 years of age with haemophilia A or B who have developed inhibitors and have been prescribed on-demand treatment of activated recombinant human factor VII at any dose for treatment of mild to moderate spontaneous bleeds | Drug: eptacog alfa (activated)<br>* Treatment of patients experiencing bleeds at the discretion of the physician/caregiver<br>* Other names: activated recombinant human factor VII;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Bleed Treatments Resulting in Effective Bleed Resolution (All Bleed Episodes) | The percentage of bleed treatments successfully resulting in bleed resolution. Analysis only considers the patient's opinion of effectiveness at 9 hours, with a rating of Effective considered as successful treatment. | within 9 hours of first injection | 
| Percentage of Bleed Treatments Resulting in Effective Bleed Resolution (Spontaneous Bleed Episodes) | The percentage of bleed treatments successfully resulting in bleed resolution. Analysis only considers the patient's opinion of effectiveness at 9 hours, with a rating of Effective considered as successful treatment. | within 9 hours of first injection | 
| Percentage of Bleed Treatments Resulting in Effective Pain Relief (All Bleed Episodes) | The percentage of participants with effective pain relief. Pain relief was a subjective assessment made by the patient during treatment of a bleed episode. | within 9 hours of first injection | 
| Percentage of Bleed Treatments Resulting in Effective Pain Relief (Spontaneous Bleed Episodes) | The percentage of participants with effective pain relief. Pain relief was a subjective assessment made by the patient during treatment of a bleed episode. | within 9 hours of first injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Bleed Treatments Resulting in Effective Haemostasis (Cessation of Bleeds) by Time Point (All Bleed Episodes) | Effective haemostasis at 3 different time points for all bleeds. Patient reported outcomes are reported over 1 hour, 3 hours and 6 hours. | 1 hour, 3 hours and 6 hours, respectively, after first injection | 
| Percentage of Bleed Treatments Resulting in Effective Haemostasis (Cessation of Bleeds) by Time Point (Spontaneous Bleed Episodes) | Effective haemostasis at 3 different time points for all bleeds. Patient reported outcomes are reported over 1 hour, 3 hours and 6 hours. | 1 hour, 3 hours and 6 hours, respectively, after first injection | 
| Percentage of Bleed Treatments Resulting in Effective Pain Relief by Time Point (All Bleed Episodes) | Effective pain relief at 3 different time points for all bleeds. Patient reported outcomes are reported over 1 hour, 3 hours and 6 hours. | 1 hour, 3 hours and 6 hours, respectively, after first injection | 
| Percentage of Bleed Treatments Resulting in Effective Pain Relief by Time Point (Spontaneous Bleed Episodes) | Effective pain relief at 3 different time points for spontaneous bleeds. Patient reported outcomes are reported over 1 hour, 3 hours and 6 hours. | 1 hour, 3 hours and 6 hours, respectively, after first injection | 
| Total Number of Injections (All Bleed Episodes) | The median number of injections required to treat individual bleed episodes. | individual bleed episode | 
| Total Number of Injections (Spontaneous Bleed Episodes) | The median number of injections required to treat individual bleed episodes. | individual bleed episode | 
| Total Exposure (Cumulative Dose) to Activated Recombinant Human Factor VII (All Bleed Episodes) | The median total cumulative dose required to treat individual bleed episodes. | individual bleed episode | 
| Total Exposure (Cumulative Dose) to Activated Recombinant Human Factor VII (Spontaneous Bleed Episodes) | The median total cumulative dose required to treat individual bleed episodes. | individual bleed episode | 
| Percentage of Patients Reporting Satisfaction With Symptom Relief (All Bleed Episodes) | Patient rate of satisfaction with symptom relief for the bleed episode overall on a 7-point Likert scale. Completion of questionnaire was voluntary. A Likert scale is an ordered, multiple choice questionnaire from which respondents choose one option that best aligns with their view of the particular outcome being measured. Scale answers ranged from extremely satisfied to extremely dissatisfied. The percentage of bleed episodes for which patients reported extremely satisfied, very satisfied or satisfied is presented. | duration of bleed episode | 
| Percentage of Bleed Treatments Resulting in Patient Satisfaction With Symptom Relief (Spontaneous Bleed Episodes) | Patient rate of satisfaction with symptom relief for the bleed episode overall on a 7-point Likert scale. Completion of questionnaire was voluntary. A Likert scale is an ordered, multiple choice questionnaire from which respondents choose one option that best aligns with their view of the particular outcome being measured. Scale answers ranged from extremely satisfied to extremely dissatisfied. The percentage of bleed episodes for which patients reported extremely satisfied, very satisfied or satisfied is presented. | duration of bleed episode | 
| Percentage of Bleed Treatments Resulting in Patient Satisfaction With Ease of Use (All Bleed Episodes) | Rate of ease of use related to activated recombinant human factor VII on a 7-point Likert scale. Completion of questionnaire was voluntary. A Likert scale is an ordered, multiple choice questionnaire from which respondents choose one option that best aligns with their view of the particular outcome being measured. Scale answers ranged from extremely difficult to extremely easy. The percentage of bleed episodes for which patients reported extremely easy, very easy or easy is presented. | duration of bleed episode | 
| Percentage of Bleed Treatments Resulting in Patient Satisfaction With Ease of Use (Spontaneous Bleed Episodes) | Rate of ease of use related to activated recombinant human factor VII on a 7-point Likert scale. Completion of questionnaire was voluntary. A Likert scale is an ordered, multiple choice questionnaire from which respondents choose one option that best aligns with their view of the particular outcome being measured. Scale answers ranged from extremely difficult to extremely easy. The percentage of bleed episodes for which patients reported extremely easy, very easy or easy is presented. | duration of bleed episode | 
| Overall Time to Cessation of Bleed/Achievement of Haemostasis (All Bleed Episodes) | Median time to achievement of haemostasis/bleed cessation calculated using Kaplan Meier life table methods. If approximately 50% or less of bleeds achieved the endpoint in a given initial dose subgroup, the median cannot be calculated and it is reported as not applicable | duration of bleed episode | 
| Overall Time to Cessation of Bleed/Achievement of Haemostasis (Spontaneous Bleed Episodes) | Median time to achievement of haemostasis/bleed cessation calculated using Kaplan Meier life table methods. If approximately 50% or less of bleeds achieved the endpoint in a given initial dose subgroup, the median cannot be calculated and it is reported as not applicable | duration of bleed episode | 
| Overall Time to Cessation/Achievement of Haemostasis (Spontaneous Bleed Episodes) | Median time to achievement of haemostasis/bleed cessation calculated using Kaplan Meier life table methods. If approximately 50% or less of bleeds achieved the endpoint in a given initial dose subgroup, the median cannot be calculated and it is reported as not applicable. | duration of bleed episode | 
| Childrens' Health Related Quality of Life (Haemo-QoL): Overall Score | The Haemo-QoL is a specific multidimensional validated and reliable questionnaire used to assess quality of life in patients with haemophilia. Scores are reported on a 0 to 100 scale-higher scores indicate more impairment. | Baseline (week 0) and and registry discontinuation (up to 28 months) | 
| Adults' Health Related Quality of Life (Haemo-QoL-A): Overall Score | The adult Haemo-QoL-A is a specific multidimensional validated and reliable questionnaire used to assess quality of life in patients with haemophilia. Scores are reported on a 0 to 100 scale-higher scores indicate more impairment. | Baseline (week 0) and and registry discontinuation (up to 28 months) |