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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novo Nordisk A/S
ClinicalTrials.gov Identifier:
NCT00703911
First received: June 19, 2008
Last updated: August 6, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention
Congenital Bleeding Disorder
Haemophilia A With Inhibitors
Haemophilia B With Inhibitors
Drug: activated recombinant human factor VII

Study Type: Observational
Study Design: Time Perspective: Prospective
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Novo Nordisk A/S:

Primary Outcome Measures:
  • Percentage of Bleed Treatments Resulting in Effective Bleed Resolution (All Bleed Episodes) [ Time Frame: within 9 hours of first injection ] [ Designated as safety issue: No ]
    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.

  • Percentage of Bleed Treatments Resulting in Effective Bleed Resolution (Spontaneous Bleed Episodes) [ Time Frame: within 9 hours of first injection ] [ Designated as safety issue: No ]
    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.

  • Percentage of Bleed Treatments Resulting in Effective Pain Relief (All Bleed Episodes) [ Time Frame: within 9 hours of first injection ] [ Designated as safety issue: No ]
    The percentage of participants with effective pain relief. Pain relief was a subjective assessment made by the patient during treatment of a bleed episode.

  • Percentage of Bleed Treatments Resulting in Effective Pain Relief (Spontaneous Bleed Episodes) [ Time Frame: within 9 hours of first injection ] [ Designated as safety issue: No ]
    The percentage of participants with effective pain relief. Pain relief was a subjective assessment made by the patient during treatment of a bleed episode.


Secondary Outcome Measures:
  • Percentage of Bleed Treatments Resulting in Effective Haemostasis (Cessation of Bleeds) by Time Point (All Bleed Episodes) [ Time Frame: 1 hour, 3 hours and 6 hours, respectively, after first injection ] [ Designated as safety issue: No ]
    Effective haemostasis at 3 different time points for all bleeds. Patient reported outcomes are reported over 1 hour, 3 hours and 6 hours.

  • Percentage of Bleed Treatments Resulting in Effective Haemostasis (Cessation of Bleeds) by Time Point (Spontaneous Bleed Episodes) [ Time Frame: 1 hour, 3 hours and 6 hours, respectively, after first injection ] [ Designated as safety issue: No ]
    Effective haemostasis at 3 different time points for all bleeds. Patient reported outcomes are reported over 1 hour, 3 hours and 6 hours.

  • Percentage of Bleed Treatments Resulting in Effective Pain Relief by Time Point (All Bleed Episodes) [ Time Frame: 1 hour, 3 hours and 6 hours, respectively, after first injection ] [ Designated as safety issue: No ]
    Effective pain relief at 3 different time points for all bleeds. Patient reported outcomes are reported over 1 hour, 3 hours and 6 hours.

  • Percentage of Bleed Treatments Resulting in Effective Pain Relief by Time Point (Spontaneous Bleed Episodes) [ Time Frame: 1 hour, 3 hours and 6 hours, respectively, after first injection ] [ Designated as safety issue: No ]
    Effective pain relief at 3 different time points for spontaneous bleeds. Patient reported outcomes are reported over 1 hour, 3 hours and 6 hours.

  • Total Number of Injections (All Bleed Episodes) [ Time Frame: individual bleed episode ] [ Designated as safety issue: No ]
    The median number of injections required to treat individual bleed episodes.

  • Total Number of Injections (Spontaneous Bleed Episodes) [ Time Frame: individual bleed episode ] [ Designated as safety issue: No ]
    The median number of injections required to treat individual bleed episodes.

  • Total Exposure (Cumulative Dose) to Activated Recombinant Human Factor VII (All Bleed Episodes) [ Time Frame: individual bleed episode ] [ Designated as safety issue: No ]
    The median total cumulative dose required to treat individual bleed episodes.

  • Total Exposure (Cumulative Dose) to Activated Recombinant Human Factor VII (Spontaneous Bleed Episodes) [ Time Frame: individual bleed episode ] [ Designated as safety issue: No ]
    The median total cumulative dose required to treat individual bleed episodes.

  • Percentage of Patients Reporting Satisfaction With Symptom Relief (All Bleed Episodes) [ Time Frame: duration of bleed episode ] [ Designated as safety issue: No ]
    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.

  • Percentage of Bleed Treatments Resulting in Patient Satisfaction With Symptom Relief (Spontaneous Bleed Episodes) [ Time Frame: duration of bleed episode ] [ Designated as safety issue: No ]
    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.

  • Percentage of Bleed Treatments Resulting in Patient Satisfaction With Ease of Use (All Bleed Episodes) [ Time Frame: duration of bleed episode ] [ Designated as safety issue: No ]
    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.

  • Percentage of Bleed Treatments Resulting in Patient Satisfaction With Ease of Use (Spontaneous Bleed Episodes) [ Time Frame: duration of bleed episode ] [ Designated as safety issue: No ]
    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.

  • Overall Time to Cessation of Bleed/Achievement of Haemostasis (All Bleed Episodes) [ Time Frame: duration of bleed episode ] [ Designated as safety issue: No ]
    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

  • Overall Time to Cessation of Bleed/Achievement of Haemostasis (Spontaneous Bleed Episodes) [ Time Frame: duration of bleed episode ] [ Designated as safety issue: No ]
    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

  • Overall Time to Cessation/Achievement of Haemostasis (Spontaneous Bleed Episodes) [ Time Frame: duration of bleed episode ] [ Designated as safety issue: No ]
    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.

  • Childrens' Health Related Quality of Life (Haemo-QoL): Overall Score [ Time Frame: Baseline (week 0) and and registry discontinuation (up to 28 months) ] [ Designated as safety issue: No ]
    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.

  • Adults' Health Related Quality of Life (Haemo-QoL-A): Overall Score [ Time Frame: Baseline (week 0) and and registry discontinuation (up to 28 months) ] [ Designated as safety issue: No ]
    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.


Other Outcome Measures:
  • Percentage of Bleed Treatments Resulting in Effective Haemostasis (Cessation of Bleed) by Dose Level (All Bleed Episodes) [ Time Frame: within 9 hours after first injection ] [ Designated as safety issue: No ]
    Percentage of bleeds with effective haemostasis within 9 hours of first injection of activated recombinant human factor VII. Patient reported assessments were sorted into 3 sub-categories: "effective" = bleed resolved or substantially improved; "partially effective" = bleed with some improvement; "ineffective" = bleed with no change or with worsening.

  • Percentage of Bleed Treatments Resulting in Effective Haemostasis (Cessation of Bleed) by Dose Level (Spontaneous Bleed Episodes) [ Time Frame: within 9 hours after first injection ] [ Designated as safety issue: No ]
    Percentage of bleeds with effective haemostasis within 9 hours of first injection of activated recombinant human factor VII. Patient reported assessments were sorted into 3 sub-categories: "effective" = bleed resolved or substantially improved; "partially effective" = bleed with some improvement; "ineffective" = bleed with no change or with worsening.

  • Percentage of Bleed Treatments Resulting in Effective Pain Relief by Initial Dose (All Bleed Episodes) [ Time Frame: within 9 hours after first injection ] [ Designated as safety issue: No ]
    Percentage of bleeds with effective pain relief within 9 hours of first injection of activated recombinant human factor VII. Patient reported assessments were sorted into 3 sub-categories: "Better" = pain resolved or decreased substantially; "Same" = no change; "Worsened" = pain worsening.

  • Percentage of Bleed Treatments Resulting in Effective Pain Relief by Initial Dose (Spontaneous Bleed Episodes) [ Time Frame: within 9 hours after first injection ] [ Designated as safety issue: No ]
    Percentage of bleeds with effective pain relief within 9 hours of first injection of activated recombinant human factor VII. Patient reported assessments were sorted into 3 sub-categories: "Better" = pain resolved or decreased substantially; "Same" = no change; "Worsened" = pain worsening.


Enrollment: 102
Study Start Date: March 2008
Study Completion Date: July 2010
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
activated recombinant human factor VII
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: activated recombinant human factor VII
Treatment of patients experiencing bleeds at the discretion of the physician/caregiver

  Eligibility

Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Patients with haemophilia A or B with inhibitors, using activated recombinant human factor VII as on-demand treatment

Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00703911

Locations
Algeria
Algiers, Algeria, 16035
Austria
Vienna, Austria, A-1010
Belgium
Brussels, Belgium, 1070
Czech Republic
Prague, Czech Republic, 16000
France
Paris La défense cedex, France, 92932
Germany
Mainz, Germany, 55127
Italy
Rome, Italy, 00144
Netherlands
Alphen a/d Rijn, Netherlands
Poland
Warszawa, Poland, PL-02-274
Portugal
Paco de Arcos, Portugal, 2780-730
Saudi Arabia
Riyadh, Saudi Arabia, 3542
South Africa
Sandton, South Africa, 2146
Sweden
Malmö, Sweden, 202 15
Turkey
Istanbul, Turkey, 34335
United Kingdom
Crawley, United Kingdom, RH11 9RT
Venezuela
Caracas, Venezuela
Sponsors and Collaborators
Novo Nordisk A/S
Investigators
Study Director: Paulo André Palhares de Miranda Novo Nordisk Health Care AG
  More Information

Additional Information:
No publications provided

Responsible Party: Novo Nordisk A/S
ClinicalTrials.gov Identifier: NCT00703911     History of Changes
Other Study ID Numbers: F7HAEM-3507
Study First Received: June 19, 2008
Results First Received: July 29, 2011
Last Updated: August 6, 2014
Health Authority: Algeria: Ministry of Health
Austria: The Austrian Agency for Health and Food Safety (AGES)
Belgium: Federal Agency for Medicines and Healthcare Products
Czech Republic: State Institute for Drug Control
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medicinal Devices (BfarM)
Italy: AIFA, National Medicines Agency
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Poland: The Office for Reg. of Medicinal Products, Medical Devices and Biocidal Products - Central Register of Clinical Trials
Portugal: INFARMED
Saudi Arabia: Ministry of Health
South Africa: Medicines Control Council
Sweden: Medical Products Agency
Turkey: Ministry of Health Drug and Pharmaceutical Department
United Kingdom: Medicines and Healthcare Regulatory Authority (MHRA)
Venezuela: Ministry of Health

Additional relevant MeSH terms:
Hemophilia A
Hemophilia B
Blood Coagulation Disorders
Hemostatic Disorders
Blood Coagulation Disorders, Inherited
Cardiovascular Diseases
Coagulation Protein Disorders
Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Hematologic Diseases
Hemorrhagic Disorders
Vascular Diseases
Factor VIII
Coagulants
Hematologic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014