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| Name | Class |
|---|---|
| University of Pavia | OTHER |
| GlaxoSmithKline | INDUSTRY |
| Azienda Ospedaliera di Padova | OTHER |
| Azienda Ospedaliera di Perugia |
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The term MYH9-related disease (MYH9RD) includes four genetic disorders: May-Hegglin anomaly, Sebastian syndrome, Fechtner syndrome, and Epstein syndrome. All these disorders derive from mutation of a unique gene, named MYH9, and they have been recognized as different clinical presentations of a single illness that was named MYH9RD. All patients affected by MYH9RD present since birth with thrombocytopenia, which can result in a variable degree of bleeding diathesis; some of them subsequently develop additional clinical manifestations, such as renal damage, sensorineural hearing loss, and/or presenile cataracts. Eltrombopag is an oral thrombopoietin receptor agonist that stimulates proliferation and differentiation of megakaryocytes, the bone marrow cells that produce blood platelets. This drug is effective in increasing platelet count in healthy volunteers, as well as in patients affected by some acquired thrombocytopenias, such as idiopathic thrombocytopenic purpura and HCV related thrombocytopenia. The purpose of this study is to determine if eltrombopag, administered orally at the dose of 50 or 75 mg/daily for up to 6 weeks, is effective in increasing platelet count of patients affected by MYH9RD. Further aims of this study are to test if eltrombopag is effective in reducing bleeding tendency of MYH9RD patients; to evaluate safety and tolerability of eltrombopag in patients with MYH9RD; to evaluate in vitro function of platelets produced during therapy in patients responding to this drug.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| eltrombopag | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| eltrombopag | Drug | Eltrombopag, administered orally, 50 mg/daily for 21 days. Patients with platelet counts between 100 and 150x10e9/L at day 21 will continue eltrombopag 50 mg/daily for 21 additional days. Patients with platelet count lower than 100x10e9/L at day 21 will receive eltrombopag 75 mg/daily for additional 21 days. Patients with more than 150x10e9 platelets/L at day 21 will stop therapy. |
| Measure | Description | Time Frame |
|---|---|---|
| Response to Drug Based on Platelet Count at the End of Therapy | The primary endpoints were the achievement of a platelet count over 100 x10e9/L or at least 3 times the baseline value (major response), or at least twice the baseline value but less than major response (minor response). The overall response to therapy is reported. Platelet count was measured at the end of therapy (21 or 42 days, see study design) by phase-contrast microscopy. | 21 days and/or 42 days of therapy, 15 and 30 days after the end of therapy |
| Measure | Description | Time Frame |
|---|---|---|
| Bleeding Tendency Assessed by WHO Bleeding Score | The percentage of patients with bleeding diathesis (grade 1, i.e. cutaneous bleeding, or grade 2, i.e. mild blood loss, according to WHO bleeding score) was calculated at baseline and at the end of therapy. The results are expressed as the mean change in the percentage of patients with bleeding diathesis (95%CI). | 21 days and/or 42 days of therapy, 15 and 30 days after the end of therapy |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Carlo Balduini, MD | IRCCS Policlinico San Matteo Foundation, Pavia, Italy | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Azienda Ospedaliero-Universitaria di Padova, Unità di Medicina Generale e Patologia Speciale | Padova | 35128 | Italy | |||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 10973259 | Background | Seri M, Cusano R, Gangarossa S, Caridi G, Bordo D, Lo Nigro C, Ghiggeri GM, Ravazzolo R, Savino M, Del Vecchio M, d'Apolito M, Iolascon A, Zelante LL, Savoia A, Balduini CL, Noris P, Magrini U, Belletti S, Heath KE, Babcock M, Glucksman MJ, Aliprandis E, Bizzaro N, Desnick RJ, Martignetti JA. Mutations in MYH9 result in the May-Hegglin anomaly, and Fechtner and Sebastian syndromes. The May-Heggllin/Fechtner Syndrome Consortium. Nat Genet. 2000 Sep;26(1):103-5. doi: 10.1038/79063. | |
| 11935325 |
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Patients enrolled between January 2009 and January 2010 as outpatients in medical clinic
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| ID | Title | Description |
|---|---|---|
| FG000 | Eltrombopag | Eltrombopag, administered orally, 50 mg/daily for 21 days. Patients with platelet counts between 100 and 150x10e9/L at day 21 continued eltrombopag 50 mg/daily for 21 additional days. Patients with platelet count lower than 100x10e9/L at day 21 received eltrombopag 75 mg/daily for additional 21 days. Patients with more than 150x10e9 platelets/L at day 21 stopped therapy. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Eltrombopag | Eltrombopag, administered orally, 50 mg/daily for 21 days. Patients with platelet counts between 100 and 150x10e9/L at day 21 continued eltrombopag 50 mg/daily for 21 additional days. Patients with platelet count lower than 100x10e9/L at day 21 received eltrombopag 75 mg/daily for additional 21 days. Patients with more than 150x10e9 platelets/L at day 21 stopped therapy. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Response to Drug Based on Platelet Count at the End of Therapy | The primary endpoints were the achievement of a platelet count over 100 x10e9/L or at least 3 times the baseline value (major response), or at least twice the baseline value but less than major response (minor response). The overall response to therapy is reported. Platelet count was measured at the end of therapy (21 or 42 days, see study design) by phase-contrast microscopy. | Posted | Number | 95% Confidence Interval | percentage of participants | 21 days and/or 42 days of therapy, 15 and 30 days after the end of therapy |
|
51 or 72 days, i.e. during the administration of Eltrombopag (21 or 42 days, see study design) and until 30 days after the end of treatment (see study design).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Eltrombopag | Eltrombopag, administered orally, 50 mg/daily for 21 days. Patients with platelet counts between 100 and 150x10e9/L at day 21 continued eltrombopag 50 mg/daily for 21 additional days. Patients with platelet count lower than 100x10e9/L at day 21 received eltrombopag 75 mg/daily for additional 21 days. Patients with more than 150x10e9 platelets/L at day 21 stopped therapy. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| headache | General disorders | mild and transient headache at the beginning of the treatment, duration 3-4 days, spontaneous remission |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Prof. Carlo Balduini | IRCCS Policlinico San Matteo Foundation | 0039.0382.502580 | c.balduini@smatteo.pv.it |
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| ID | Term |
|---|---|
| D001791 | Blood Platelet Disorders |
| ID | Term |
|---|---|
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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| ID | Term |
|---|---|
| C520809 | eltrombopag |
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| OTHER |
| Fondazione Telethon | OTHER |
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|
|
| All Types of Adverse Events | All type of adverse events were registered.Results indicate the number of participants who experience a side effect of the drug. | 21 days and/or 42 days of therapy, 15 and 30 days after the end of therapy |
| in Vitro Function of Platelets Produced During Therapy in Responding Patients | in vitro platelet function will be assessed in patients achieving a platelet count of 100 x10e9/L or more at the end of the therapy | 21 days or 42 days of therapy |
| Fondazione IRCCS Policlinico San Matteo, Unità di Medicina III |
| Pavia |
| 27100 |
| Italy |
| Policlinico Monteluce, Sezione di Medicina Interna e Cardiovascolare | Perugia | 06122 | Italy |
| Background |
| Seri M, Savino M, Bordo D, Cusano R, Rocca B, Meloni I, Di Bari F, Koivisto PA, Bolognesi M, Ghiggeri GM, Landolfi R, Balduini CL, Zelante L, Ravazzolo R, Renieri A, Savoia A. Epstein syndrome: another renal disorder with mutations in the nonmuscle myosin heavy chain 9 gene. Hum Genet. 2002 Feb;110(2):182-6. doi: 10.1007/s00439-001-0659-1. Epub 2001 Dec 14. |
| 12792306 | Background | Seri M, Pecci A, Di Bari F, Cusano R, Savino M, Panza E, Nigro A, Noris P, Gangarossa S, Rocca B, Gresele P, Bizzaro N, Malatesta P, Koivisto PA, Longo I, Musso R, Pecoraro C, Iolascon A, Magrini U, Rodriguez Soriano J, Renieri A, Ghiggeri GM, Ravazzolo R, Balduini CL, Savoia A. MYH9-related disease: May-Hegglin anomaly, Sebastian syndrome, Fechtner syndrome, and Epstein syndrome are not distinct entities but represent a variable expression of a single illness. Medicine (Baltimore). 2003 May;82(3):203-15. doi: 10.1097/01.md.0000076006.64510.5c. |
| 18046028 | Background | Bussel JB, Cheng G, Saleh MN, Psaila B, Kovaleva L, Meddeb B, Kloczko J, Hassani H, Mayer B, Stone NL, Arning M, Provan D, Jenkins JM. Eltrombopag for the treatment of chronic idiopathic thrombocytopenic purpura. N Engl J Med. 2007 Nov 29;357(22):2237-47. doi: 10.1056/NEJMoa073275. |
| 18046027 | Background | McHutchison JG, Dusheiko G, Shiffman ML, Rodriguez-Torres M, Sigal S, Bourliere M, Berg T, Gordon SC, Campbell FM, Theodore D, Blackman N, Jenkins J, Afdhal NH; TPL102357 Study Group. Eltrombopag for thrombocytopenia in patients with cirrhosis associated with hepatitis C. N Engl J Med. 2007 Nov 29;357(22):2227-36. doi: 10.1056/NEJMoa073255. |
| 20844233 | Derived | Pecci A, Gresele P, Klersy C, Savoia A, Noris P, Fierro T, Bozzi V, Mezzasoma AM, Melazzini F, Balduini CL. Eltrombopag for the treatment of the inherited thrombocytopenia deriving from MYH9 mutations. Blood. 2010 Dec 23;116(26):5832-7. doi: 10.1182/blood-2010-08-304725. Epub 2010 Sep 15. |
| Participants |
|
| Age Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
|
|
| Secondary | Bleeding Tendency Assessed by WHO Bleeding Score | The percentage of patients with bleeding diathesis (grade 1, i.e. cutaneous bleeding, or grade 2, i.e. mild blood loss, according to WHO bleeding score) was calculated at baseline and at the end of therapy. The results are expressed as the mean change in the percentage of patients with bleeding diathesis (95%CI). | Posted | Mean | 95% Confidence Interval | participants | 21 days and/or 42 days of therapy, 15 and 30 days after the end of therapy |
|
|
|
| Secondary | All Types of Adverse Events | All type of adverse events were registered.Results indicate the number of participants who experience a side effect of the drug. | Posted | Number | number of participants | 21 days and/or 42 days of therapy, 15 and 30 days after the end of therapy |
|
|
|
| Secondary | in Vitro Function of Platelets Produced During Therapy in Responding Patients | in vitro platelet function will be assessed in patients achieving a platelet count of 100 x10e9/L or more at the end of the therapy | Posted | Number | participants | 21 days or 42 days of therapy |
|
|
|
| 0 |
| 12 |
| 2 |
| 12 |
|
| dry mouth | General disorders | transient sensation o dry mouth at the beginning of the treatment, duration 3-4 days, spontaneous remission |
|
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