ThrombocytopeniaPhase 2NCT02298933
Complement Inhibition Using Eculizumab to Overcome Platelet Transfusion Refractoriness in Patients With Severe Thrombocytopenia
A Phase 2 study testing Eculizumab in people with Thrombocytopenia and Alloimmune Platelet Refractoriness, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
Trial summary
Background: Platelets are tiny cells in the blood that help stop bleeding. Thrombocytopenia happens when people do not have enough normal platelets. Getting a transfusion of another person s platelets can help stop too much bleeding. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Thrombocytopenia, Alloimmune Platelet Refractoriness
- What is being tested?
- Eculizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Nov 2014to 8 Aug 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Ages 18-75 years inclusive.
- Ability to comprehend the investigational nature of the study and provide informed consent.
- Thrombocytopenia (due to congenital causes, bone marrow failure, hematologic malignancies, and treatment related), defined as <10k/uL without bleeding or <30K/uL with evidence of life threatening bleeding (intracranial hemorrhage, GI bleeding, pulmonary hemorrhage, uncontrolled epistaxis, hematuria).
- Diagnosed with immune platelet refractoriness, characterized by all of the following:
- Lack of adequate post-transfusion platelet count increment, defined by, CCI <7500/ul at 10-60 min, and CCI <5000/ul at 18-24 hrs (in those who had a CCI at 10-60 min greater than or equal to 5000/microl)after at least 2 consecutive transfusions.
- Presence of anti-HLA class A and/or B antibody.
Who cannot join
- Active meningococcal infection.
- Severe psychiatric illness. Mental deficiency sufficiently severe as to make making informed consent impossible.
- Positive pregnancy test for women of childbearing age within 1 week.
- HIV positive test within 3 months
- Paroxysmal Nocturnal Hemoglobinuria (PNH) disease with evidence of intravascular hemolysis.
- Presence ITP/autoimmune thrombocytopenia
Show all 10Show fewer
- Immune platelet refractoriness responsive to treatment with IVIG
- RE-ENROLLMENT CRITERIA:
- Meet response criteria to the initial treatment or second treatment
- Meets all initial inclusion/exclusion criteria
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Background:
- Platelets are tiny cells in the blood that help stop bleeding. Thrombocytopenia happens when people do not have enough normal platelets. Getting a transfusion of another person s platelets can help stop too much bleeding. But because these cells are from other people, the body may reject them,putting them at risk for serious bleeding complications. This conditions is called alloimmune platelet refractoriness . There are evidence that in many patients, platelet counts fail to increase after a platelet transfusion because the transfused platelets are destroyed by the body s defence soldier, called complement . Researchers want to see if a drug, that inhibits complement, can help increase platelet levels and reduce bleeding
Read more
Objectives:
- To see if eculizumab increases platelet levels more after a transfusion. To see if it reduces the chance of bleeding too much.
Eligibility:
- Adults 18-75 years old who have thrombocytopenia and alloimmune platelet refractoriness.
Design:
- Participants will be screened with medical history, physical exam, and blood tests.
- Participants will have the procedures listed below. They can have them while they are in the hospital. Or they can go to the outpatient clinic for them. Each visit may take up to 3 hours.
- Participants will get a meningitis vaccine if needed. Then they will get the study drug as an infusion.
- Participants will have a platelet transfusion. Their blood will be drawn every 24 hours until the platelet count is less than 10,000 per 1 microliter of blood.
- They will take antibiotics for 14 days.
- Participants will have a checkup and blood drawn twice a week for 2 weeks. They will get more transfusions if needed.
Read the detailed description
Platelet transfusion can be a life-saving procedure in preventing or treating serious bleeding in patients who have low and/or dysfunctional platelets. Treatment of blood cancer and other blood diseases as well as bone marrow transplantation is not possible without platelet transfusion support. Unfortunately, 20-60% of chronically transfused patients will stop responding to these transfusions putting them at risk for serious bleeding complications. Data support the concept that in many patients, platelet counts fail to increase after a platelet transfusion because the transfused platelets are destroyed by the body s complement. In order to overcome this problem, we will inhibit complement activity with the medication eculizumab that specifically binds and suppresses complement. We hypothesize that when we treat patients who have platelet refractoriness with eculizumab, the platelet counts will increase to higher numbers after platelet transfusions, decreasing the risk of bleeding complications associated with having a low platelet count.
- Being tested
- Eculizumab
- Keywords
- Complement Inhibition, Platelet Refractoriness, Eculizumab
- Medical subject headings
- Thrombocytopenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EculizumabDrug
300 mg single-use vials
| Study group | Role | What they receive |
|---|---|---|
| Eculizumab | Experimental | 1200 mg IV infusion over 30-40 min Receives: Drug: Eculizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Subjects With Sustained Platelet Transfusion Responsiveness
To evaluate the safety and efficacy of eculizumab to increase the platelet increment, defined as Corrected Count Increment (CCI) >7500/μL at 10-60 min together with CCI>5000/μL at 18-24 hrs post transfusion in patients with platelet refractoriness following treatment with eculizumab and platelet transfusion.
Measured: 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Nov 2014 (estimated)
- Study start21 Nov 2014
- Primary completion8 Aug 2017
- Study completion8 Aug 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for ThrombocytopeniaStudies of the same condition, open and under way.
- More trials run by National Heart, Lung, and Blood Institute (NHLBI)The 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
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Georg Aue, M.D., Principal investigator, National Heart, Lung, and Blood Institute (NHLBI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02298933
- Sponsor's protocol ID
- 150015
- Other IDs
- 15-H-0015
- Status last verified
- 18 Jan 2018
- First submitted
- 21 Nov 2014
- Last updated
- 3 Jan 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Vo P, Purev E, West KA, McDuffee E, Worthy T, Cook L, Hawks G, Wells B, Shalabi R, Flegel WA, Adams SD, Reger R, Aue G, Tian X, Childs R. A pilot trial of complement inhibition using eculizumab to overcome platelet transfusion refractoriness in human leukocyte antigen allo-immunized patients. Br J Haematol. 2020 May;189(3):551-558. doi: 10.1111/bjh.16385. Epub 2020 Feb 21.
PubMed 32086819
Study at a glance
From the registry record, last updated by the sponsor on 3 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Complement Inhibition Using Eculizumab to Overcome Platelet Transfusion Refractoriness in Patients With Severe Thrombocytopenia
- ClinicalTrials.gov ID
- NCT02298933
- Acronym / sponsor ID
- 150015
- Keywords
- Complement Inhibition, Platelet Refractoriness, Eculizumab
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- 21 Nov 2014
- Primary completion
- 8 Aug 2017 (actual)
- Study completion
- 8 Aug 2017 (actual)
- First posted
- 24 Nov 2014 (estimated)
- Results
- Posted 3 Jan 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
- Platelets are tiny cells in the blood that help stop bleeding. Thrombocytopenia happens when people do not have enough normal platelets. Getting a transfusion of another person s platelets can help stop too much bleeding. But because these cells are from other people, the body may reject them,putting them at risk for serious bleeding complications. This conditions is called alloimmune platelet refractoriness . There are evidence that in many patients, platelet counts fail to increase after a platelet transfusion because the transfused platelets are destroyed by the body s defence soldier, called complement . Researchers want to see if a drug, that inhibits complement, can help increase platelet levels and reduce bleeding
Objectives:
- To see if eculizumab increases platelet levels more after a transfusion. To see if it reduces the chance of bleeding too much.
Eligibility:
- Adults 18-75 years old who have thrombocytopenia and alloimmune platelet refractoriness.
Design:
- Participants will be screened with medical history, physical exam, and blood tests.
- Participants will have the procedures listed below. They can have them while they are in the hospital. Or they can go to the outpatient clinic for them. Each visit may take up to 3 hours.
- Participants will get a meningitis vaccine if needed. Then they will get the study drug as an infusion.
- Participants will have a platelet transfusion. Their blood will be drawn every 24 hours until the platelet count is less than 10,000 per 1 microliter of blood.
- They will take antibiotics for 14 days.
- Participants will have a checkup and blood drawn twice a week for 2 weeks. They will get more transfusions if needed.
Detailed description
Platelet transfusion can be a life-saving procedure in preventing or treating serious bleeding in patients who have low and/or dysfunctional platelets. Treatment of blood cancer and other blood diseases as well as bone marrow transplantation is not possible without platelet transfusion support. Unfortunately, 20-60% of chronically transfused patients will stop responding to these transfusions putting them at risk for serious bleeding complications. Data support the concept that in many patients, platelet counts fail to increase after a platelet transfusion because the transfused platelets are destroyed by the body s complement. In order to overcome this problem, we will inhibit complement activity with the medication eculizumab that specifically binds and suppresses complement. We hypothesize that when we treat patients who have platelet refractoriness with eculizumab, the platelet counts will increase to higher numbers after platelet transfusions, decreasing the risk of bleeding complications associated with having a low platelet count.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Eculizumab | Experimental | Drug: Eculizumab1200 mg IV infusion over 30-40 min |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Ages 18-75 years inclusive.
- Ability to comprehend the investigational nature of the study and provide informed consent.
- Thrombocytopenia (due to congenital causes, bone marrow failure, hematologic malignancies, and treatment related), defined as <10k/uL without bleeding or <30K/uL with evidence of life threatening bleeding (intracranial hemorrhage, GI bleeding, pulmonary hemorrhage, uncontrolled epistaxis, hematuria).
- Diagnosed with immune platelet refractoriness, characterized by all of the following:
Key exclusion criteria (10 listed)
- Active meningococcal infection.
- Severe psychiatric illness. Mental deficiency sufficiently severe as to make making informed consent impossible.
- Positive pregnancy test for women of childbearing age within 1 week.
- HIV positive test within 3 months
- Paroxysmal Nocturnal Hemoglobinuria (PNH) disease with evidence of intravascular hemolysis.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Eculizumab300 mg single-use vials | Drug | Eculizumab |
Primary outcome
Number of Subjects With Sustained Platelet Transfusion Responsiveness
Time frame: 24 hours
To evaluate the safety and efficacy of eculizumab to increase the platelet increment, defined as Corrected Count Increment (CCI) >7500/μL at 10-60 min together with CCI>5000/μL at 18-24 hrs post transfusion in patients with platelet refractoriness following treatment with eculizumab and platelet transfusion.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jan 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32086819Vo P, Purev E, West KA, McDuffee E, Worthy T, Cook L, Hawks G, Wells B, Shalabi R, Flegel WA, Adams SD, Reger R, Aue G, Tian X, Childs R. A pilot trial of complement inhibition using eculizumab to overcome platelet transfusion refractoriness in human leukocyte antigen allo-immunized patients. Br J Haematol. 2020 May;189(3):551-558. doi: 10.1111/bjh.16385. Epub 2020 Feb 21.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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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.
Georg Aue, M.D. principal investigator
National Heart, Lung, and Blood Institute (NHLBI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Eculizumab in people with Thrombocytopenia and Alloimmune Platelet Refractoriness, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site 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 6 inclusion and 10 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 3 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Jan 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Subjects With Sustained Platelet Transfusion Responsiveness (time frame: 24 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02298933, which also lists 1 linked publication.
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 3 Jan 2019.