Immune ThrombocytopeniaNCT03377439
The Association Between Platelet Reactivity and Bleeding Risk in Adult ITP
An observational study of Immune Thrombocytopenia, run by Shandong University at 1 site in China.
Trial summary
It seems reasonable to assume that patients who present significant bleeding symptoms may have different quality of platelets than those without bleeding. This question was addressed in a study that examined platelet function in adult ITP patients, which try to determine whether this correlated with bleeding risk. Read more about this study
- Who is it for?
- Ages 18 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Immune Thrombocytopenia
- What is being tested?
- Platelet function tests
- How many people
- 400 participants
- Where
- 1 siteChina
- Study dates
- 1 Dec 2017to Dec 2018
- 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 18 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Untreated adult ITP patients of both genders between the ages of 18 and 80 years.
Who may be able to join
- Untreated adult ITP patients of both genders between the ages of 18 and 80 years.
- Participants of either acute or chronic phase; with or without thrombocytopenia; with or without bleeding manifestation.
Who cannot join
- Received high-dose steroids or IVIG within 3 weeks prior to the test.
- Received second-line ITP-specific treatments (eg, cyclophosphamide, 6-mercaptopurine, vincristine, vinblastine, etc) within 3 months prior to the test.
- Current HIV infection, hepatitis B virus or hepatitis C virus infections.
- Severe medical condition (liver and kidney function impairment).
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Qilu Hospital, Shandong University
Jinan, Shandong, 250012
Ming Hou, MD, PhD
About this study
Official title: The Association Between Platelet Reactivity and Bleeding Risk in Adult ITP Patients: a Prospective Multicenter Double-blind Study
It seems reasonable to assume that patients who present significant bleeding symptoms may have different quality of platelets than those without bleeding. This question was addressed in a study that examined platelet function in adult ITP patients, which try to determine whether this correlated with bleeding risk. Previous reports have suggested that measuring platelet function may help define patients at highest risk of bleeding. In addition, Middelburg and colleagues corrected platelet function for quartile of platelet count, using <32×10^9/L as the lowest cohort and >132×10^9/L as the top quartile. They demonstrated that increased platelet reactivity (as measured by flow cytometry) was associated with decreased risk of bleeding but particularly for those patients with the lowest platelet counts. Further studies in a larger cohort are needed to confirm this correlation. Our study aimed at standardizing a prediction model to evaluate the bleeding risk of adult ITP patients with the use of platelet function tests.
Read the detailed description
The investigators are undertaking a prospective multicenter double-blind study of 400 adult patients with immune thrombocytopenia from 6 medical centers in China. We adopted three different assays that examined platelet function and reactivity. 1) Flow cytometry: Citrate anticoagulated whole blood was diluted in PBS to result in 20×10^9/L platelets, and 20 μl was aliquoted into polystyrene test tubes. Ten microliters of anti-CD42b-PE was added and incubated at room temperature for 10 min. Agonists (TRAP-6 12.5 μMol/L, Collagen 20 μg/mL, ADP 2 μM, Epinephrin 20 μM, Arachidonic acid 0.275 mM, Ristocetin 1.5 mg/mL) or PBS were added (10 μl each) and incubated again for 10 min. Then mAb PAC-1-FITC or anti-CD62p-FITC (10 μl each) or the corresponding isotype-matched controls were added. After 15-min incubation in the dark, the reaction was stopped with 500 μl PBS. Samples were analyzed on a flow cytometer (FACScan, Becton-Dickinson) by measuring 10,000 events in the CD42b-positive fraction. 2) Filopodia quantification: Briefly, platelets in Tyrode's buffer were allowed to adhere to VWF (9×10^6 cells/coverslip) in the presence of botrocetin (1 μg/mL) and Integrilin (40 μg/mL) at 37°C. After 15 min, non-adherent platelets were removed by washing and adherent platelets were fixed with 4% PFA, stained with TRITC-phalloidin (2 μg/mL) and viewed by epifluorescence microscopy for filopodia count. 3) Platelet aggregation: Measured on an automated platelet aggregation analyzer.
Understanding bleeding risk and underlying determinants of bleeding is important in order to help recognize patients that will require pharmacologic therapy even at higher platelet counts. Previous studies have suggested that low platelet counts, increased patient age, use of concurrent medications, and male sex are associated with increased bleeding risk. The present investigation will answer whether platelet function predicts the severity of bleeding in adult ITP patients. Clinical information of recruited participants includes gender, age, platelet count and physical/laboratory examination. Blinding was set between investigators who evaluated bleeding risks and those who performed experiments.
- Conditions
- Immune Thrombocytopenia
- Being tested
- Platelet function tests
- Keywords
- Platelet function, Bleeding risk, Immune Thrombocytopenia
- Medical subject headings
- Purpura, Thrombocytopenic, Idiopathic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Platelet function testsOther
Platelet reactivity was measured by flow cytometry, filopodia detection and the platelet aggregation analyzer.
| Study group | Role | What they receive |
|---|---|---|
| Group A | Participants with platelet counts <32×10^9/L. Receives: Other: Platelet function tests | |
| Group B | Participants with platelet counts between 32×10^9/L and 132×10^9/L. Receives: Other: Platelet function tests | |
| Group C | Participants with platelet counts >132×10^9/L. Receives: Other: Platelet function tests |
What is being measured
The primary outcome is the main question the study is designed to answer.
The severity of bleeding manifestations at onset was assessed using a previously described clinical scoring system with minor modifications. The total bleeding score was calculated by adding the scores for each item.
The bleeding score system: 1) Age: Age over 65 years (2'); Age over 75 years (5'). 2) Cutaneous bleeding: Localized petechial purpura (1'); Localized ecchymotic purpura (2'); Two locations of petechial purpura (2'); Generalized petechial purpura (3'); Generalized ecchymotic purpura (4'). 3) Mucosal bleeding: Unilateral epistaxis (2'); Bilateral epistaxis (3'); Hemorrhagic oral bullae and/or gingival bleeding (5'). 4) Gastrointestinal bleeding: Gastrointestinal hemorrhage without anemia (4'); Gastrointestinal hemorrhage with acute anemia and/or shock (15'). 5) Urinary bleeding: Macroscopic hematuria without anemia (4'); Macroscopic hematuria with acute anemia (10'). 6) Genitourinary tract bleeding: Major meno/metrorrhagia without anemia (4'); Major meno/metrorrhagia with acute anemia (10'). 7) Central nervous system bleeding: Central nervous system bleeding and/or life-threatening hemorrhage (15').
Measured: No more than three months after platelet function assessment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Dec 2017
- Study start1 Dec 2017
- Primary completionDec 2018 (estimated)
- Study completionDec 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Immune ThrombocytopeniaStudies of the same condition, open and under way.
- 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
- 400 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shandong University
- Sponsor type
- University, hospital or other
- Collaborators
- Traditional Chinese Medicine Hospital Affiliated to Shandong University, Jinan Central Hospital, Qianfoshan Hospital, Shandong Provincial Hospital, Shandong University Second Hospital
- Responsible party
- Principal investigator, Ming Hou, Shandong University
- Investigators
- Jun Peng, MD, PhD, Study director, Qilu Hospital of Shandong University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03377439
- Sponsor's protocol ID
- Plt function and bleeding risk
- Status last verified
- Dec 2017
- First submitted
- 14 Dec 2017
- Last updated
- 19 Dec 2017
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Khellaf M, Michel M, Schaeffer A, Bierling P, Godeau B. Assessment of a therapeutic strategy for adults with severe autoimmune thrombocytopenic purpura based on a bleeding score rather than platelet count. Haematologica. 2005 Jun;90(6):829-32.
PubMed 15951296Middelburg RA, Roest M, Ham J, Coccoris M, Zwaginga JJ, van der Meer PF. Flow cytometric assessment of agonist-induced P-selectin expression as a measure of platelet quality in stored platelet concentrates. Transfusion. 2013 Aug;53(8):1780-7. doi: 10.1111/trf.12001. Epub 2012 Dec 7.
PubMed 23216254Middelburg RA, Carbaat-Ham JC, Hesam H, Ragusi MA, Zwaginga JJ. Platelet function in adult ITP patients can be either increased or decreased, compared to healthy controls, and is associated with bleeding risk. Hematology. 2016 Oct;21(9):549-51. doi: 10.1080/10245332.2016.1180097. Epub 2016 May 9.
PubMed 27159138Panzer S, Hocker L, Koren D. Agonists-induced platelet activation varies considerably in healthy male individuals: studies by flow cytometry. Ann Hematol. 2006 Feb;85(2):121-5. doi: 10.1007/s00277-005-0029-5. Epub 2005 Nov 10.
PubMed 16283308Panzer S, Rieger M, Vormittag R, Eichelberger B, Dunkler D, Pabinger I. Platelet function to estimate the bleeding risk in autoimmune thrombocytopenia. Eur J Clin Invest. 2007 Oct;37(10):814-9. doi: 10.1111/j.1365-2362.2007.01855.x. Epub 2007 Aug 28.
PubMed 17727674Mangin P, Yuan Y, Goncalves I, Eckly A, Freund M, Cazenave JP, Gachet C, Jackson SP, Lanza F. Signaling role for phospholipase C gamma 2 in platelet glycoprotein Ib alpha calcium flux and cytoskeletal reorganization. Involvement of a pathway distinct from FcR gamma chain and Fc gamma RIIA. J Biol Chem. 2003 Aug 29;278(35):32880-91. doi: 10.1074/jbc.M302333200. Epub 2003 Jun 17.
PubMed 12813055Maurer E, Tang C, Schaff M, Bourdon C, Receveur N, Ravanat C, Eckly A, Hechler B, Gachet C, Lanza F, Mangin PH. Targeting platelet GPIbbeta reduces platelet adhesion, GPIb signaling and thrombin generation and prevents arterial thrombosis. Arterioscler Thromb Vasc Biol. 2013 Jun;33(6):1221-9. doi: 10.1161/ATVBAHA.112.301013. Epub 2013 Apr 4.
PubMed 23559635
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Association Between Platelet Reactivity and Bleeding Risk in Adult ITP Patients: a Prospective Multicenter Double-blind Study
- ClinicalTrials.gov ID
- NCT03377439
- Acronym / sponsor ID
- Plt function and bleeding risk
- Conditions
- Immune Thrombocytopenia
- Keywords
- Platelet function, Bleeding risk, Immune Thrombocytopenia
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 400 participants (estimated)
- Lead sponsor
- Shandong UniversityUniversity, hospital or other
- Collaborators
- Traditional Chinese Medicine Hospital Affiliated to Shandong University, Jinan Central Hospital, Qianfoshan Hospital, Shandong Provincial Hospital, Shandong University Second Hospital
- Study start
- 1 Dec 2017 (actual)
- Primary completion
- Dec 2018 (estimated)
- Study completion
- Dec 2018 (estimated)
- First posted
- 19 Dec 2017 (actual)
- 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.
It seems reasonable to assume that patients who present significant bleeding symptoms may have different quality of platelets than those without bleeding. This question was addressed in a study that examined platelet function in adult ITP patients, which try to determine whether this correlated with bleeding risk. Previous reports have suggested that measuring platelet function may help define patients at highest risk of bleeding. In addition, Middelburg and colleagues corrected platelet function for quartile of platelet count, using <32×10^9/L as the lowest cohort and >132×10^9/L as the top quartile. They demonstrated that increased platelet reactivity (as measured by flow cytometry) was associated with decreased risk of bleeding but particularly for those patients with the lowest platelet counts. Further studies in a larger cohort are needed to confirm this correlation. Our study aimed at standardizing a prediction model to evaluate the bleeding risk of adult ITP patients with the use of platelet function tests.
Detailed description
The investigators are undertaking a prospective multicenter double-blind study of 400 adult patients with immune thrombocytopenia from 6 medical centers in China. We adopted three different assays that examined platelet function and reactivity. 1) Flow cytometry: Citrate anticoagulated whole blood was diluted in PBS to result in 20×10^9/L platelets, and 20 μl was aliquoted into polystyrene test tubes. Ten microliters of anti-CD42b-PE was added and incubated at room temperature for 10 min. Agonists (TRAP-6 12.5 μMol/L, Collagen 20 μg/mL, ADP 2 μM, Epinephrin 20 μM, Arachidonic acid 0.275 mM, Ristocetin 1.5 mg/mL) or PBS were added (10 μl each) and incubated again for 10 min. Then mAb PAC-1-FITC or anti-CD62p-FITC (10 μl each) or the corresponding isotype-matched controls were added. After 15-min incubation in the dark, the reaction was stopped with 500 μl PBS. Samples were analyzed on a flow cytometer (FACScan, Becton-Dickinson) by measuring 10,000 events in the CD42b-positive fraction. 2) Filopodia quantification: Briefly, platelets in Tyrode's buffer were allowed to adhere to VWF (9×10^6 cells/coverslip) in the presence of botrocetin (1 μg/mL) and Integrilin (40 μg/mL) at 37°C. After 15 min, non-adherent platelets were removed by washing and adherent platelets were fixed with 4% PFA, stained with TRITC-phalloidin (2 μg/mL) and viewed by epifluorescence microscopy for filopodia count. 3) Platelet aggregation: Measured on an automated platelet aggregation analyzer.
Understanding bleeding risk and underlying determinants of bleeding is important in order to help recognize patients that will require pharmacologic therapy even at higher platelet counts. Previous studies have suggested that low platelet counts, increased patient age, use of concurrent medications, and male sex are associated with increased bleeding risk. The present investigation will answer whether platelet function predicts the severity of bleeding in adult ITP patients. Clinical information of recruited participants includes gender, age, platelet count and physical/laboratory examination. Blinding was set between investigators who evaluated bleeding risks and those who performed experiments.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Group A | – | Other: Platelet function testsParticipants with platelet counts <32×10^9/L. |
| Group B | – | Other: Platelet function testsParticipants with platelet counts between 32×10^9/L and 132×10^9/L. |
| Group C | – | Other: Platelet function testsParticipants with platelet counts >132×10^9/L. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Untreated adult ITP patients of both genders between the ages of 18 and 80 years.
Key inclusion criteria (2 listed)
- Untreated adult ITP patients of both genders between the ages of 18 and 80 years.
- Participants of either acute or chronic phase; with or without thrombocytopenia; with or without bleeding manifestation.
Key exclusion criteria (4 listed)
- Received high-dose steroids or IVIG within 3 weeks prior to the test.
- Received second-line ITP-specific treatments (eg, cyclophosphamide, 6-mercaptopurine, vincristine, vinblastine, etc) within 3 months prior to the test.
- Current HIV infection, hepatitis B virus or hepatitis C virus infections.
- Severe medical condition (liver and kidney function impairment).
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 |
|---|---|---|
| Platelet function testsPlatelet reactivity was measured by flow cytometry, filopodia detection and the platelet aggregation analyzer. | Other | Group A, Group B, Group C |
Primary outcome
The severity of bleeding manifestations at onset was assessed using a previously described clinical scoring system with minor modifications. The total bleeding score was calculated by adding the scores for each item.
Time frame: No more than three months after platelet function assessment.
The bleeding score system: 1) Age: Age over 65 years (2'); Age over 75 years (5'). 2) Cutaneous bleeding: Localized petechial purpura (1'); Localized ecchymotic purpura (2'); Two locations of petechial purpura (2'); Generalized petechial purpura (3'); Generalized ecchymotic purpura (4'). 3) Mucosal bleeding: Unilateral epistaxis (2'); Bilateral epistaxis (3'); Hemorrhagic oral bullae and/or gingival bleeding (5'). 4) Gastrointestinal bleeding: Gastrointestinal hemorrhage without anemia (4'); Gastrointestinal hemorrhage with acute anemia and/or shock (15'). 5) Urinary bleeding: Macroscopic hematuria without anemia (4'); Macroscopic hematuria with acute anemia (10'). 6) Genitourinary tract bleeding: Major meno/metrorrhagia without anemia (4'); Major meno/metrorrhagia with acute anemia (10'). 7) Central nervous system bleeding: Central nervous system bleeding and/or life-threatening hemorrhage (15').
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2017.
- Background: PubMed 15951296Khellaf M, Michel M, Schaeffer A, Bierling P, Godeau B. Assessment of a therapeutic strategy for adults with severe autoimmune thrombocytopenic purpura based on a bleeding score rather than platelet count. Haematologica. 2005 Jun;90(6):829-32.
- Background: PubMed 23216254Middelburg RA, Roest M, Ham J, Coccoris M, Zwaginga JJ, van der Meer PF. Flow cytometric assessment of agonist-induced P-selectin expression as a measure of platelet quality in stored platelet concentrates. Transfusion. 2013 Aug;53(8):1780-7. doi: 10.1111/trf.12001. Epub 2012 Dec 7.
- Background: PubMed 27159138Middelburg RA, Carbaat-Ham JC, Hesam H, Ragusi MA, Zwaginga JJ. Platelet function in adult ITP patients can be either increased or decreased, compared to healthy controls, and is associated with bleeding risk. Hematology. 2016 Oct;21(9):549-51. doi: 10.1080/10245332.2016.1180097. Epub 2016 May 9.
- Background: PubMed 16283308Panzer S, Hocker L, Koren D. Agonists-induced platelet activation varies considerably in healthy male individuals: studies by flow cytometry. Ann Hematol. 2006 Feb;85(2):121-5. doi: 10.1007/s00277-005-0029-5. Epub 2005 Nov 10.
- Background: PubMed 17727674Panzer S, Rieger M, Vormittag R, Eichelberger B, Dunkler D, Pabinger I. Platelet function to estimate the bleeding risk in autoimmune thrombocytopenia. Eur J Clin Invest. 2007 Oct;37(10):814-9. doi: 10.1111/j.1365-2362.2007.01855.x. Epub 2007 Aug 28.
- Background: PubMed 12813055Mangin P, Yuan Y, Goncalves I, Eckly A, Freund M, Cazenave JP, Gachet C, Jackson SP, Lanza F. Signaling role for phospholipase C gamma 2 in platelet glycoprotein Ib alpha calcium flux and cytoskeletal reorganization. Involvement of a pathway distinct from FcR gamma chain and Fc gamma RIIA. J Biol Chem. 2003 Aug 29;278(35):32880-91. doi: 10.1074/jbc.M302333200. Epub 2003 Jun 17.
- Background: PubMed 23559635Maurer E, Tang C, Schaff M, Bourdon C, Receveur N, Ravanat C, Eckly A, Hechler B, Gachet C, Lanza F, Mangin PH. Targeting platelet GPIbbeta reduces platelet adhesion, GPIb signaling and thrombin generation and prevents arterial thrombosis. Arterioscler Thromb Vasc Biol. 2013 Jun;33(6):1221-9. doi: 10.1161/ATVBAHA.112.301013. Epub 2013 Apr 4.
- 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.
Jun Peng, MD, PhD study director
Qilu Hospital of Shandong University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Immune Thrombocytopenia, run by Shandong University at 1 site in China.
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 2 inclusion and 4 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: status not confirmed, as of the sponsor's last update on 19 Dec 2017. 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 China. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Ming Hou Hou, MD, PhD (86-531-82169879, qlhouming@sina.com.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The severity of bleeding manifestations at onset was assessed using a previously described clinical scoring system with minor modifications. The total bleeding score was calculated by adding the scores for each item. (time frame: No more than three months after platelet function assessment.). 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 NCT03377439, which also lists 7 linked publications.
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 19 Dec 2017.