Hemophilia APASsNCT01571934
Inhibitor Development in Patients With Hemophilia A Undergoing Surgery
An observational study of Hemophilia A, run by Emory University at 7 sites in United States.
Trial summary
Hemophilia A is a genetic deficiency of factor VIII that causes blood to clot too slowly. The disease is classified based on how much factor VIII is in the blood. People with mild or moderate hemophilia A have low, but detectable, blood levels of factor VIII and bleed with trauma or surgery. Read more about this study
- Who is it for?
- Any age, men only
- Conditions the study is for
- Hemophilia A
- How many people
- 30 participants
- Where
- 7 sitesUnited States
- Study dates
- Nov 2011to Mar 2016
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- Men only
- No healthy volunteers
- Child, Adult, Older adult
Study population: In addition to Emory University, subjects will be recruited at one of 8 following sites: University of Pittsburgh, University of North Carolina, Oregon Health and Science University, University of Colorado, University of Texas Health Science Center at Houston, University of Minnesota, and Indiana Hemophilia Treatment Center.
Who may be able to join
- Males with mild/moderate hemophilia A (fVIII activity 1-40%)
- Planned surgical intervention which is anticipated to require 5 consecutive days of fVIII replacement therapy (These can be outpatient or inpatient treatment days.)
- Weight >22.5 kg (To assure that volumes of blood to be drawn for study purposes are safe.)
Who cannot join
- Past history of an inhibitor (inhibitor titer >0.4 BU/ml)
- HIV infection with CD4 count <400/ul
- Currently receiving immunosuppressive medication(s)
- Unable to tolerate quantity of blood to be drawn
- Current or past diagnosis autoimmune disorder
- Current or past diagnosis of immune deficiency disorder other than HIV
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
Emory University Comprehensive Hemophilia Treatment Center
Atlanta, Georgia, 30322
University of Colorado, Hemophilia and Thrombosis Center
Aurora, Colorado, 80045
University of North Carolina
Chapel Hill, North Carolina, 27599-7035
The University of Texas Health Science Center at Houston
Houston, Texas, 77030
Indiana Hemophilia and Thrombosis Center
Indianapolis, Indiana, 46260
University of Pittsburgh and Hemophilia Center of Pennsylvania
Pittsburgh, Pennsylvania, 15213
Oregon Health & Science University
Portland, Oregon, 97239
About this study
Hemophilia A is a genetic deficiency of factor VIII that causes blood to clot too slowly. The disease is classified based on how much factor VIII is in the blood. People with mild or moderate hemophilia A have low, but detectable, blood levels of factor VIII and bleed with trauma or surgery. At the time of surgery, they need to receive factor VIII replacement by infusion into the vein so that blood can clot normally and abnormal bleeding can be avoided. A complication of hemophilia A is the development of an antibody that binds factor VIII and makes the factor VIII infused for treatment not work properly. This antibody is called an inhibitor. In mild and moderate hemophilia A, inhibitors are not common, but have been reported to occur after intensive factor VIII infusions, as may occur at the time of surgery. This study is designed to observe people with mild and moderate hemophilia A who are having surgery. Information on the surgery, treatments given, bleeding, and infection will be gathered. Also, blood will be drawn to determine how the immune system is reacting to the factor VIII. No specific treatments will be given as part of this study. We will use the information to determine what influences inhibitor development. A better understanding of inhibitor development will help medical providers do things to avoid inhibitor development in this population or researchers to design new treatments.
Read the detailed description
The development of neutralizing anti-factor VIII (fVIII) antibodies, fVIII inhibitor, is the most significant complication affecting patients with hemophilia A (HA). Once an inhibitor develops, treatment is less effective and costly. Although inhibitors occur most commonly in those with severe HA, 25% of new inhibitors occur in those with non-severe HA. In patients with non-severe HA, the development of a fVIII inhibitor can change the course of disease from one that is easily managed to one with the potential for spontaneous life-threatening difficult to treat bleeding. Although significant advances have been made in understanding risk factors for fVIII inhibitor development in patients with severe HA, studies that seek to understand the risk for fVIII inhibitor development in those with non-severe disease have been limited to retrospective analyses. In these retrospective analyses, intensive fVIII treatment and surgery have been identified as risk factors for fVIII inhibitor development in non-severe HA. Additionally, receiving fVIII by continuous infusion has been associated with fVIII inhibitor development in non-severe HA in some but not all studies and may be due in part to a more robust proinflammatory response during continuous infusion. Accordingly, the next logical step to evaluate the risk of inhibitor development associated with continuous fVIII infusion is a prospective observational cohort study. Additionally, knowledge of the immune response to fVIII in the surgical setting is essential for identification of patients at high risk for inhibitor development and development of strategies to prevent inhibitor development and is best evaluated in the setting of an prospective cohort study.
This multicenter prospective observational cohort study will enroll a total of 140 subjects at 10 centers who have mild or moderate hemophilia a (fVIII activity 1-40%) who are scheduled to undergo surgery for which at least 5 consecutive days of fVIII replacement therapy is required. The study will gather clinical data and collect blood specimens on 4 occasions over a 3 month period. Outcomes include: inhibitor development, total fVIII usage, bleeding, and markers of T cell activation.
- Conditions
- Hemophilia A
- Keywords
- Hemophilia A
- Medical subject headings
- Hemophilia A
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Mild or moderate hemophilia A | Subjects with mild or moderate hemophilia A (fVIII activity 1-40%) who are scheduled to undergo surgery for which at least 5 consecutive days of fVIII replacement therapy is required. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Inhibitor development (inhibitor titer > 0.4 BU/ml)
Primary Study Endpoint: Inhibitor development (inhibitor titer > 0.4 BU/ml) by post-operative (POD) day 90. Three months or 90 days was selected as the primary end point based on data collected in the case-control study where 17/18 cases had developed their inhibitor within 12 weeks of their intensive fVIII treatment and only 1 case developed the inhibitor >16 weeks after the intensive fVIII treatment.
Measured: postopereratvie date 90
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Apr 2012 (estimated)
- Study startNov 2011
- Primary completionFeb 2016
- Study completionMar 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hemophilia AStudies of the same condition, open and under way.
- More trials run by Emory UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Christine Kempton, MD, MSc, Emory University
- Investigators
- Christine Kempton, MD, MSc, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01571934
- Sponsor's protocol ID
- IRB00046800
- Other IDs
- 5K23HL105785, PASs
- Acronym
- PASs
- Status last verified
- Apr 2017
- First submitted
- 4 Apr 2012
- Last updated
- 26 Apr 2017
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 26 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Inhibitor Development in Patients With Hemophilia A Undergoing Surgery
- ClinicalTrials.gov ID
- NCT01571934
- Acronym / sponsor ID
- PASs / IRB00046800
- Conditions
- Hemophilia A
- Keywords
- Hemophilia A
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Nov 2011
- Primary completion
- Feb 2016 (actual)
- Study completion
- Mar 2016 (actual)
- First posted
- 5 Apr 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Hemophilia A is a genetic deficiency of factor VIII that causes blood to clot too slowly. The disease is classified based on how much factor VIII is in the blood. People with mild or moderate hemophilia A have low, but detectable, blood levels of factor VIII and bleed with trauma or surgery. At the time of surgery, they need to receive factor VIII replacement by infusion into the vein so that blood can clot normally and abnormal bleeding can be avoided. A complication of hemophilia A is the development of an antibody that binds factor VIII and makes the factor VIII infused for treatment not work properly. This antibody is called an inhibitor. In mild and moderate hemophilia A, inhibitors are not common, but have been reported to occur after intensive factor VIII infusions, as may occur at the time of surgery. This study is designed to observe people with mild and moderate hemophilia A who are having surgery. Information on the surgery, treatments given, bleeding, and infection will be gathered. Also, blood will be drawn to determine how the immune system is reacting to the factor VIII. No specific treatments will be given as part of this study. We will use the information to determine what influences inhibitor development. A better understanding of inhibitor development will help medical providers do things to avoid inhibitor development in this population or researchers to design new treatments.
Detailed description
The development of neutralizing anti-factor VIII (fVIII) antibodies, fVIII inhibitor, is the most significant complication affecting patients with hemophilia A (HA). Once an inhibitor develops, treatment is less effective and costly. Although inhibitors occur most commonly in those with severe HA, 25% of new inhibitors occur in those with non-severe HA. In patients with non-severe HA, the development of a fVIII inhibitor can change the course of disease from one that is easily managed to one with the potential for spontaneous life-threatening difficult to treat bleeding. Although significant advances have been made in understanding risk factors for fVIII inhibitor development in patients with severe HA, studies that seek to understand the risk for fVIII inhibitor development in those with non-severe disease have been limited to retrospective analyses. In these retrospective analyses, intensive fVIII treatment and surgery have been identified as risk factors for fVIII inhibitor development in non-severe HA. Additionally, receiving fVIII by continuous infusion has been associated with fVIII inhibitor development in non-severe HA in some but not all studies and may be due in part to a more robust proinflammatory response during continuous infusion. Accordingly, the next logical step to evaluate the risk of inhibitor development associated with continuous fVIII infusion is a prospective observational cohort study. Additionally, knowledge of the immune response to fVIII in the surgical setting is essential for identification of patients at high risk for inhibitor development and development of strategies to prevent inhibitor development and is best evaluated in the setting of an prospective cohort study.
This multicenter prospective observational cohort study will enroll a total of 140 subjects at 10 centers who have mild or moderate hemophilia a (fVIII activity 1-40%) who are scheduled to undergo surgery for which at least 5 consecutive days of fVIII replacement therapy is required. The study will gather clinical data and collect blood specimens on 4 occasions over a 3 month period. Outcomes include: inhibitor development, total fVIII usage, bleeding, and markers of T cell activation.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Mild or moderate hemophilia A | – | –Subjects with mild or moderate hemophilia A (fVIII activity 1-40%) who are scheduled to undergo surgery for which at least 5 consecutive days of fVIII replacement therapy is required. |
Who may qualify
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- In addition to Emory University, subjects will be recruited at one of 8 following sites: University of Pittsburgh, University of North Carolina, Oregon Health and Science University, University of Colorado, University of Texas Health Science Center at Houston, University of Minnesota, and Indiana Hemophilia Treatment Center.
Key inclusion criteria (3 listed)
- Males with mild/moderate hemophilia A (fVIII activity 1-40%)
- Planned surgical intervention which is anticipated to require 5 consecutive days of fVIII replacement therapy (These can be outpatient or inpatient treatment days.)
- Weight >22.5 kg (To assure that volumes of blood to be drawn for study purposes are safe.)
Key exclusion criteria (6 listed)
- Past history of an inhibitor (inhibitor titer >0.4 BU/ml)
- HIV infection with CD4 count <400/ul
- Currently receiving immunosuppressive medication(s)
- Unable to tolerate quantity of blood to be drawn
- Current or past diagnosis autoimmune disorder
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Inhibitor development (inhibitor titer > 0.4 BU/ml)
Time frame: postopereratvie date 90
Primary Study Endpoint: Inhibitor development (inhibitor titer > 0.4 BU/ml) by post-operative (POD) day 90. Three months or 90 days was selected as the primary end point based on data collected in the case-control study where 17/18 cases had developed their inhibitor within 12 weeks of their intensive fVIII treatment and only 1 case developed the inhibitor >16 weeks after the intensive fVIII treatment.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Apr 2017.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christine Kempton, MD, MSc principal investigator
Emory University
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hemophilia A, run by Emory University at 7 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Inhibitor development (inhibitor titer > 0.4 BU/ml) (time frame: postopereratvie date 90). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Apr 2017.