Idiopathic Thrombocytopenic PurpuraNCT03412188
The Effect of Eltrombopag on the Expression of Platelet Collagen Receptor GPVI in Pediatric ITP.
A study testing Eltrombopag and conventional in people with Idiopathic Thrombocytopenic Purpura, run by Nayera Hazaa Elsherif at 1 site in Egypt.
Trial summary
Using eltronmobag as an alternative pathway, which depend on stimulation of thrombocyte synthesis, in chronic and persistent immune thrombocytopenia may be more promising treatment than the classic type, not only by increasing platelets count but also through enhancing of the platelets activation and upregulation of… Read more about this study
- Who is it for?
- Ages 1 year to 18 years
- Conditions the study is for
- Idiopathic Thrombocytopenic Purpura
- What is being tested?
- Eltrombopag and conventional
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteEgypt
- Study dates
- 1 Aug 2018to 1 Sep 2021
- Phase
- Interventional
- 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 1 year to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Age ≥ 1 to ≤ 18 years at enrollment. Patient should be able to swallow tablet form. Weight should be ≥ 12kg.
- Diagnosis of persistent (3-<12 months duration) or chronic cases (≥12 months duration) with day 1 platelet count ≤ 20x10^9.
- Patients have a bleeding score grade 3 for skin and/or grade 2 or higher for mucosal domains and/or higher than grade 1 for organ domain at the baseline visit or the worst bleeding incident episode in the patient's medical reports in the last 3 months prior screening, using ITP-BAT (v1.0) score.
- Normal Kidney function tests and liver function tests.
Who cannot join
- Acute thrombocytopenic purpura patients or Other causes of thrombocytopenia. Patients with Evans syndrome
- Hypertension, cardiovascular disease, diabetes, hepatitis C virus (HCV), HIV, hepatitis B surface antigen(HBsAg) seropositive status.
- Baseline bone marrow biopsy with evident fibrosis (reticulin stain grade 2 or more)
- Patients who have previously received eltrombopag.
Trial locations and contacts
1 site in 1 country.
Egypt1 site
Ainshams University , Faculty of medicine , Pediatric Hematology&Oncology unit, children hospital.
Cairo, 11579
About this study
Official title: Evaluation of the Effect of Eltrombopag on the Expression of Platelet Collagen Receptor Glycoprotein VI (GPVI) in Pediatric Patients With Chronic and Persistent Immune Thrombocytopenia.
Using eltronmobag as an alternative pathway, which depend on stimulation of thrombocyte synthesis, in chronic and persistent immune thrombocytopenia may be more promising treatment than the classic type, not only by increasing platelets count but also through enhancing of the platelets activation and upregulation of GPVI expression on platelet surface.
This study will include 40 pediatric patients with chronic or persistent ITP, recruited from the Hematology clinic of pediatric hospital Ain Shams University, aiming to investigate the efficacy, \& the safety and tolerability of eltrombopag therapy for children as well as the ability of eltrombopag to enhance the platelet activation through the up-regulation of glycoprotein VI (GPVI) receptor expression in comparison with other lines of treatment.
Read more
Patients will be divided into 2 groups : Group 1 on eltrombopag ; Group 2 : receiving other lines of therapy .
All Patients will be subjected to :
- bleeding score assessment ( baseline \&every month ) and Health related quality of life based on Kids' ITP Tools (KIT) questionnaires( baseline and week 24 )
- Baseline and at week 24 bone marrow examination with reticulin stain
- clinical examination every 2 weeks and complete blood counts.
- Assessment of soluble form of glycoprotein VI using sandwich enzyme-linked immunosorbent assay (ELISA) as well as assessment of platelet activation by GPVI using flowcytometry (Gardiner, etal.,2010 ) at baseline and at the end of 6 months treatment period
Read the detailed description
Primary immune thrombocytopenia (ITP) is an acquired immune-mediated disorder characterized by isolated thrombocytopenia, defined as a peripheral blood platelet count less than 100 ×109/l and the absence of any obvious initiating and/ or underlying cause of the thrombocytopenia. (Buchanan, 1989).
Novel thrombopoiesis-stimulating agents have been developed increasing platelet production by overdriving the system and thereby correcting the thrombocytopenia (Cines etal., 2002). Because these peptides bear no structural resemblance to thrombopoietin agonist(TPO) but still bind and activate the TPO receptor, these compounds are called TPO receptor agonists (TRAs). (Meletis etal.,2010).
Newly formed young platelets are larger and express higher levels of glycoprotein Ibα (GPIbα), which decreases as platelets age. For the purpose of quantitative platelet analysis, GPIbα of the GPIb-IX-V complex and GPVI are of particular interest because these receptors are essentially platelet specific, are critical for initiation of thrombus formation at arterial shear rates, and are implicated in wider platelet functions beyond hemostasis and thrombosis, as well as platelet aging and clearance. (Gardiner etal., 2014).
GP VI is thought to be the major signaling receptor involved in platelet activation on exposed collagen. Following GP VI interactions with collagen, platelets initiate strong activation and release the content of alpha and dense granules.( Yun etal.,2016) GPVI expression was upregulated in megakaryocytes after TPO stimulation (Holmes etal., 2002). Eltrombopag could upregulate GPVI expression in ITP patients, thereby enhancing their platelet adhesion capacity leading to reduce bleeding symptoms (Chiou etal.,2015).
The Aim is to :
To investigate the efficacy, \& the safety and tolerability of eltrombopag therapy for children with persistent and chronic immune thrombocytopenia as well as the ability of eltrombopag to enhance the platelet activation through the up-regulation of glycoprotein VI (GPVI) receptor expression in comparison with other lines of treatment.
Study methods :
This study will include 40 pediatric patients with chronic or persistent ITP, age ≥ 1 to ≤ 18 years, recruited from the Hematology clinic of pediatric hospital Ain Shams University
- Baseline bleeding score assessment (ITP-BAT (v1.0) score) and Health related quality of life based on Kids' ITP Tools (KIT) questionnaires will be done.
- Patients will be divided into 2 groups:
- Group 1 (eltrombopag arm n=20 patients): Patients who showed no response (platelet count ≤ 20x109/L) initially for 3 months or relapse after 6 months after at least one prior ITP therapy. patients will receive a total daily dose of eltrombopag of (25-50mg/d). Dose adjustments may be made based on platelets count with an increment of 25mg once per day at 2 weeks intervals (Maximum dose: 75 mg orally once a day). If platelet counts reached more than 200 × 109 per L, the dose will be decreased by 25 mg once per day at 2 weeks intervals. If platelet counts increased to more than 400 × 109 per L, treatment will be interrupted until platelet counts decreases to less than 150 × 109 per L then the dose will be resumed at the next lower dose. Patients, who responded poorly to eltrombopag in 6 months or developed adverse effects, will be asked to discontinue the medication. Those who responded will be followed for further 6 month period.
- Group 2 (n=20 patients) Patients who are currently receiving other lines of treatment (steroids, IVIG, azathioprine, and rituximab).
- All patients will be followed clinically every 2 weeks throughout the period of the study for safety and efficacy, and complete blood counts.
- Baseline and at week 24 bone marrow examination with reticulin stain will be done
- Baseline and every 3 months liver and kidney function tests. Throughout the study periods, patients with increased serum alanine transaminase (ALT) ≥ 3 times upper limit normal (ULN) with a total bilirubin ≥2 times ULN or those with increased serum ALT ≥ 5 times ULN will be withdrawn, as well as patients with increased serum creatinine above ULN.
- Adverse events, episodes of bleeding and bleeding score will be collected and evaluated every month throughout the study.
- Health related quality of life based on Kids' ITP Tools (KIT) questionnaires will be repeated at the end of study period.
- Assessment of soluble form of glycoprotein VI using sandwich enzyme-linked immunosorbent assay (ELISA) as well as assessment of platelet activation by GPVI using flowcytometry (Gardiner, etal.,2010 ) at baseline and at the end of 6 months treatment period
Statistical Analysis : Analysis of data will be done using Statistical Program for Social Science version 21 (SPSS Inc., Chicago, IL, USA).
- Conditions
- Idiopathic Thrombocytopenic Purpura
- Being tested
- Eltrombopag, conventional
- Keywords
- Chronic ITP, persistent ITP, Eltrombopag, GPVI receptor
- 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.
EltrombopagDrug
Also called Revolade
Patients who showed no response (platelet count ≤ 20x109/L) initially for 3 months or relapse after 6 months after at least one prior ITP therapy will receive a total daily dose of eltrombopag of (25-50mg/d)
conventionalDrug
Also called solumedrol, imuran, cellcept, mabthera
Patients who are currently receiving conventional lines of treatment (steroids, IVIG, azathioprine, and rituximab, Mycophenolate mofetil) will continue on the same line of treatment
| Study group | Role | What they receive |
|---|---|---|
| group 1 Eltrombopag arm | Experimental | Group 1 (eltrombopag arm n=20 patients): Patients who showed no response (platelet count ≤ 20x109/L) initially for 3 months or relapse after 6 months after at least one prior ITP therapy. patients will receive a total daily dose of eltrombopag of (25-50mg/d). Dose adjustments may be made based on platelets count with an increment of 25mg once per day at 2 weeks intervals (Maximum dose: 75 mg orally once a day).
Patients, who responded poorly to eltrombopag in 6 months or developed adverse effects, were asked to discontinue the medication. Those who responded were followed for further 6 month period. Receives: Drug: Eltrombopag |
| group 2 conventional Treatment | Active comparator | Group 2 (n=20 patients) Patients who are currently receiving other lines of treatment (steroids, IVIG, azathioprine, and rituximab).
patients will continue on the conventional line of treatment Receives: Drug: conventional |
What is being measured
The primary outcome is the main question the study is designed to answer.
Expression of glycoprotein VI collagen receptor
Percentages of patients achieving increased expression of glycoprotein VI collagen receptor
Measured: at 24 weeks
Secondary outcomes (3)
Complete response or response
Percentages of patients achieving Complete response" (CR) defined as any platelet count of 100x109/L at least once throughout the study period in the absence of rescue treatment and those achieving "Response" (R) is defined as any platelet count between 50 and 100x 109/L or doubling of the baseline count at least once throughout the study period
Measured: at 24 weeks
Maintenance of response
The maximum duration for which a patient continuously maintained a platelet count between 50 and 100x 10*9/L in the absence of rescue treatment.
Measured: at 24 weeks
Safety: Number of Patients who will have adverse events
Number of Patients who will have adverse events.
Measured: at 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2018
- Study start1 Aug 2018
- Primary completion1 Sep 2021
- Study completion1 Sep 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (15)Papers the sponsor has linked to this study.
- Other trials for Idiopathic Thrombocytopenic PurpuraStudies 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Patients will be divided into 2 groups: Group 1 (eltrombopag arm n=20 patients): Patients who showed no response (platelet count ≤ 20x109/L) initially for 3 months or relapse after 6 months after at least one prior ITP therapy. patients will receive a total daily dose of eltrombopag of (25-50mg/d). Dose adjustments may be made based on platelets count. Group 2 (n=20 patients) Patients who are currently receiving other lines of treatment (steroids, IVIG, azathioprine, and rituximab).
- Masking
- None (open label)
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nayera Hazaa Elsherif
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Nayera Hazaa Elsherif, Ain Shams University
- Investigators
- Azza AG Tantawy, MD, Principal investigator, Ain shams university, Faculty of medicine, Pediatric Hematology &Oncology department
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03412188
- Sponsor's protocol ID
- GPVI-ITP
- Status last verified
- Oct 2021
- First submitted
- 20 Jan 2018
- Last updated
- 28 Oct 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Still investigators did not decide about sharing individual participants data
Publications
Mazzucconi MG, Fazi P, Bernasconi S, De Rossi G, Leone G, Gugliotta L, Vianelli N, Avvisati G, Rodeghiero F, Amendola A, Baronci C, Carbone C, Quattrin S, Fioritoni G, D'Alfonso G, Mandelli F; Gruppo Italiano Malattie EMatologiche dell'Adulto (GIMEMA) Thrombocytopenia Working Party. Therapy with high-dose dexamethasone (HD-DXM) in previously untreated patients affected by idiopathic thrombocytopenic purpura: a GIMEMA experience. Blood. 2007 Feb 15;109(4):1401-7. doi: 10.1182/blood-2005-12-015222. Epub 2006 Oct 31.
PubMed 17077333Buchanan GR. Overview of ITP treatment modalities in children. Blut. 1989 Jul;59(1):96-104. doi: 10.1007/BF00320257.
PubMed 2665875Bussel JB, de Miguel PG, Despotovic JM, Grainger JD, Sevilla J, Blanchette VS, Krishnamurti L, Connor P, David M, Boayue KB, Matthews DC, Lambert MP, Marcello LM, Iyengar M, Chan GW, Chagin KD, Theodore D, Bailey CK, Bakshi KK. Eltrombopag for the treatment of children with persistent and chronic immune thrombocytopenia (PETIT): a randomised, multicentre, placebo-controlled study. Lancet Haematol. 2015 Aug;2(8):e315-25. doi: 10.1016/S2352-3026(15)00114-3. Epub 2015 Jul 28.
PubMed 26688484Chiou TJ, Chang YF, Wang MC, Kao CW, Lin HY, Chen TY, Hsueh EJ, Lan YJ, Sung YC, Lin SF, Bai LY, Chen CG. Eltrombopag enhances platelet adhesion by upregulating the expression of glycoprotein VI in patients with chronic immune thrombocytopenic purpura. Transl Res. 2015 Dec;166(6):750-761.e4. doi: 10.1016/j.trsl.2015.09.005. Epub 2015 Sep 30.
PubMed 26477577Cines DB, Blanchette VS. Immune thrombocytopenic purpura. N Engl J Med. 2002 Mar 28;346(13):995-1008. doi: 10.1056/NEJMra010501. No abstract available.
PubMed 11919310Ehrlich LA, Kwitkowski VE, Reaman G, Ko CW, Nie L, Pazdur R, Farrell AT. U.S. Food and Drug Administration approval summary: Eltrombopag for the treatment of pediatric patients with chronic immune (idiopathic) thrombocytopenia. Pediatr Blood Cancer. 2017 Dec;64(12). doi: 10.1002/pbc.26657. Epub 2017 Jun 19.
PubMed 28627134Gardiner EE, Andrews RK. Platelet receptor expression and shedding: glycoprotein Ib-IX-V and glycoprotein VI. Transfus Med Rev. 2014 Apr;28(2):56-60. doi: 10.1016/j.tmrv.2014.03.001. Epub 2014 Mar 12.
PubMed 24674813Gardiner EE, Thom JY, Al-Tamimi M, Hughes A, Berndt MC, Andrews RK, Baker RI. Restored platelet function after romiplostim treatment in a patient with immune thrombocytopenic purpura. Br J Haematol. 2010 May;149(4):625-8. doi: 10.1111/j.1365-2141.2010.08092.x. Epub 2010 Feb 8. No abstract available.
PubMed 20148887Grainger JD, Locatelli F, Chotsampancharoen T, Donyush E, Pongtanakul B, Komvilaisak P, Sosothikul D, Drelichman G, Sirachainan N, Holzhauer S, Lebedev V, Lemons R, Pospisilova D, Ramenghi U, Bussel JB, Bakshi KK, Iyengar M, Chan GW, Chagin KD, Theodore D, Marcello LM, Bailey CK. Eltrombopag for children with chronic immune thrombocytopenia (PETIT2): a randomised, multicentre, placebo-controlled trial. Lancet. 2015 Oct 24;386(10004):1649-58. doi: 10.1016/S0140-6736(15)61107-2. Epub 2015 Jul 28.
PubMed 26231455Holmes ML, Bartle N, Eisbacher M, Chong BH. Cloning and analysis of the thrombopoietin-induced megakaryocyte-specific glycoprotein VI promoter and its regulation by GATA-1, Fli-1, and Sp1. J Biol Chem. 2002 Dec 13;277(50):48333-41. doi: 10.1074/jbc.M206127200. Epub 2002 Sep 30.
PubMed 12359731Klaassen RJ, Blanchette VS, Barnard D, Wakefield CD, Curtis C, Bradley CS, Neufeld EJ, Buchanan GR, Silva MP, Chan AK, Young NL. Validity, reliability, and responsiveness of a new measure of health-related quality of life in children with immune thrombocytopenic purpura: the Kids' ITP Tools. J Pediatr. 2007 May;150(5):510-5, 515.e1. doi: 10.1016/j.jpeds.2007.01.037.
PubMed 17452226Rodeghiero F, Michel M, Gernsheimer T, Ruggeri M, Blanchette V, Bussel JB, Cines DB, Cooper N, Godeau B, Greinacher A, Imbach P, Khellaf M, Klaassen RJ, Kuhne T, Liebman H, Mazzucconi MG, Newland A, Pabinger I, Tosetto A, Stasi R. Standardization of bleeding assessment in immune thrombocytopenia: report from the International Working Group. Blood. 2013 Apr 4;121(14):2596-606. doi: 10.1182/blood-2012-07-442392. Epub 2013 Jan 29.
PubMed 23361904Rodeghiero F, Stasi R, Gernsheimer T, Michel M, Provan D, Arnold DM, Bussel JB, Cines DB, Chong BH, Cooper N, Godeau B, Lechner K, Mazzucconi MG, McMillan R, Sanz MA, Imbach P, Blanchette V, Kuhne T, Ruggeri M, George JN. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. Blood. 2009 Mar 12;113(11):2386-93. doi: 10.1182/blood-2008-07-162503. Epub 2008 Nov 12.
PubMed 19005182Yun SH, Sim EH, Goh RY, Park JI, Han JY. Platelet Activation: The Mechanisms and Potential Biomarkers. Biomed Res Int. 2016;2016:9060143. doi: 10.1155/2016/9060143. Epub 2016 Jun 15.
PubMed 27403440Meletis J, Katsandris A, Raptis SD, Mantzourani M. Successful treatment of Immune Thrombocytopenic Purpura (ITP) with the thrombopoietin-mimetic romiplostim. Med Sci Monit. 2010 Aug;16(8):CS100-2.
PubMed 20671616
Study at a glance
From the registry record, last updated by the sponsor on 28 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the Effect of Eltrombopag on the Expression of Platelet Collagen Receptor Glycoprotein VI (GPVI) in Pediatric Patients With Chronic and Persistent Immune Thrombocytopenia.
- ClinicalTrials.gov ID
- NCT03412188
- Acronym / sponsor ID
- GPVI-ITP
- Conditions
- Idiopathic Thrombocytopenic Purpura
- Keywords
- Chronic ITP, persistent ITP, Eltrombopag, GPVI receptor
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- Nayera Hazaa ElsherifUniversity, hospital or other
- Study start
- 1 Aug 2018 (actual)
- Primary completion
- 1 Sep 2021 (actual)
- Study completion
- 1 Sep 2021 (actual)
- First posted
- 26 Jan 2018 (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.
Using eltronmobag as an alternative pathway, which depend on stimulation of thrombocyte synthesis, in chronic and persistent immune thrombocytopenia may be more promising treatment than the classic type, not only by increasing platelets count but also through enhancing of the platelets activation and upregulation of GPVI expression on platelet surface.
This study will include 40 pediatric patients with chronic or persistent ITP, recruited from the Hematology clinic of pediatric hospital Ain Shams University, aiming to investigate the efficacy, \& the safety and tolerability of eltrombopag therapy for children as well as the ability of eltrombopag to enhance the platelet activation through the up-regulation of glycoprotein VI (GPVI) receptor expression in comparison with other lines of treatment.
Patients will be divided into 2 groups : Group 1 on eltrombopag ; Group 2 : receiving other lines of therapy .
All Patients will be subjected to :
- bleeding score assessment ( baseline \&every month ) and Health related quality of life based on Kids' ITP Tools (KIT) questionnaires( baseline and week 24 )
- Baseline and at week 24 bone marrow examination with reticulin stain
- clinical examination every 2 weeks and complete blood counts.
- Assessment of soluble form of glycoprotein VI using sandwich enzyme-linked immunosorbent assay (ELISA) as well as assessment of platelet activation by GPVI using flowcytometry (Gardiner, etal.,2010 ) at baseline and at the end of 6 months treatment period
Detailed description
Primary immune thrombocytopenia (ITP) is an acquired immune-mediated disorder characterized by isolated thrombocytopenia, defined as a peripheral blood platelet count less than 100 ×109/l and the absence of any obvious initiating and/ or underlying cause of the thrombocytopenia. (Buchanan, 1989).
Novel thrombopoiesis-stimulating agents have been developed increasing platelet production by overdriving the system and thereby correcting the thrombocytopenia (Cines etal., 2002). Because these peptides bear no structural resemblance to thrombopoietin agonist(TPO) but still bind and activate the TPO receptor, these compounds are called TPO receptor agonists (TRAs). (Meletis etal.,2010).
Newly formed young platelets are larger and express higher levels of glycoprotein Ibα (GPIbα), which decreases as platelets age. For the purpose of quantitative platelet analysis, GPIbα of the GPIb-IX-V complex and GPVI are of particular interest because these receptors are essentially platelet specific, are critical for initiation of thrombus formation at arterial shear rates, and are implicated in wider platelet functions beyond hemostasis and thrombosis, as well as platelet aging and clearance. (Gardiner etal., 2014).
GP VI is thought to be the major signaling receptor involved in platelet activation on exposed collagen. Following GP VI interactions with collagen, platelets initiate strong activation and release the content of alpha and dense granules.( Yun etal.,2016) GPVI expression was upregulated in megakaryocytes after TPO stimulation (Holmes etal., 2002). Eltrombopag could upregulate GPVI expression in ITP patients, thereby enhancing their platelet adhesion capacity leading to reduce bleeding symptoms (Chiou etal.,2015).
The Aim is to :
To investigate the efficacy, \& the safety and tolerability of eltrombopag therapy for children with persistent and chronic immune thrombocytopenia as well as the ability of eltrombopag to enhance the platelet activation through the up-regulation of glycoprotein VI (GPVI) receptor expression in comparison with other lines of treatment.
Study methods :
This study will include 40 pediatric patients with chronic or persistent ITP, age ≥ 1 to ≤ 18 years, recruited from the Hematology clinic of pediatric hospital Ain Shams University
- Baseline bleeding score assessment (ITP-BAT (v1.0) score) and Health related quality of life based on Kids' ITP Tools (KIT) questionnaires will be done.
- Patients will be divided into 2 groups:
- Group 1 (eltrombopag arm n=20 patients): Patients who showed no response (platelet count ≤ 20x109/L) initially for 3 months or relapse after 6 months after at least one prior ITP therapy. patients will receive a total daily dose of eltrombopag of (25-50mg/d). Dose adjustments may be made based on platelets count with an increment of 25mg once per day at 2 weeks intervals (Maximum dose: 75 mg orally once a day). If platelet counts reached more than 200 × 109 per L, the dose will be decreased by 25 mg once per day at 2 weeks intervals. If platelet counts increased to more than 400 × 109 per L, treatment will be interrupted until platelet counts decreases to less than 150 × 109 per L then the dose will be resumed at the next lower dose. Patients, who responded poorly to eltrombopag in 6 months or developed adverse effects, will be asked to discontinue the medication. Those who responded will be followed for further 6 month period.
- Group 2 (n=20 patients) Patients who are currently receiving other lines of treatment (steroids, IVIG, azathioprine, and rituximab).
- All patients will be followed clinically every 2 weeks throughout the period of the study for safety and efficacy, and complete blood counts.
- Baseline and at week 24 bone marrow examination with reticulin stain will be done
- Baseline and every 3 months liver and kidney function tests. Throughout the study periods, patients with increased serum alanine transaminase (ALT) ≥ 3 times upper limit normal (ULN) with a total bilirubin ≥2 times ULN or those with increased serum ALT ≥ 5 times ULN will be withdrawn, as well as patients with increased serum creatinine above ULN.
- Adverse events, episodes of bleeding and bleeding score will be collected and evaluated every month throughout the study.
- Health related quality of life based on Kids' ITP Tools (KIT) questionnaires will be repeated at the end of study period.
- Assessment of soluble form of glycoprotein VI using sandwich enzyme-linked immunosorbent assay (ELISA) as well as assessment of platelet activation by GPVI using flowcytometry (Gardiner, etal.,2010 ) at baseline and at the end of 6 months treatment period
Statistical Analysis : Analysis of data will be done using Statistical Program for Social Science version 21 (SPSS Inc., Chicago, IL, USA).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Patients will be divided into 2 groups: Group 1 (eltrombopag arm n=20 patients): Patients who showed no response (platelet count ≤ 20x109/L) initially for 3 months or relapse after 6 months after at least one prior ITP therapy. patients will receive a total daily dose of eltrombopag of (25-50mg/d). Dose adjustments may be made based on platelets count. Group 2 (n=20 patients) Patients who are currently receiving other lines of treatment (steroids, IVIG, azathioprine, and rituximab).
| Arm | Type | Receives |
|---|---|---|
| group 1 Eltrombopag arm | Experimental | Drug: EltrombopagGroup 1 (eltrombopag arm n=20 patients): Patients who showed no response (platelet count ≤ 20x109/L) initially for 3 months or relapse after 6 months after at least one prior ITP therapy. patients will receive a total daily dose of eltrombopag of (25-50mg/d). Dose adjustments may be made based on platelets count with an increment of 25mg once per day at 2 weeks intervals (Maximum dose: 75 mg orally once a day). Patients, who responded poorly to eltrombopag in 6 months or developed adverse effects, were asked to discontinue the medication. Those who responded were followed for further 6 month period. |
| group 2 conventional Treatment | Active comparator | Drug: conventionalGroup 2 (n=20 patients) Patients who are currently receiving other lines of treatment (steroids, IVIG, azathioprine, and rituximab). patients will continue on the conventional line of treatment |
Who may qualify
- Ages
- 1 year to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- Age ≥ 1 to ≤ 18 years at enrollment. Patient should be able to swallow tablet form. Weight should be ≥ 12kg.
- Diagnosis of persistent (3-<12 months duration) or chronic cases (≥12 months duration) with day 1 platelet count ≤ 20x10^9.
- Patients have a bleeding score grade 3 for skin and/or grade 2 or higher for mucosal domains and/or higher than grade 1 for organ domain at the baseline visit or the worst bleeding incident episode in the patient's medical reports in the last 3 months prior screening, using ITP-BAT (v1.0) score.
- Normal Kidney function tests and liver function tests.
Key exclusion criteria (4 listed)
- Acute thrombocytopenic purpura patients or Other causes of thrombocytopenia. Patients with Evans syndrome
- Hypertension, cardiovascular disease, diabetes, hepatitis C virus (HCV), HIV, hepatitis B surface antigen(HBsAg) seropositive status.
- Baseline bone marrow biopsy with evident fibrosis (reticulin stain grade 2 or more)
- Patients who have previously received eltrombopag.
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 |
|---|---|---|
| EltrombopagAlso: RevoladePatients who showed no response (platelet count ≤ 20x109/L) initially for 3 months or relapse after 6 months after at least one prior ITP therapy will receive a total daily dose of eltrombopag of (25-50mg/d) | Drug | group 1 Eltrombopag arm |
| conventionalAlso: solumedrol, imuran, cellcept, mabtheraPatients who are currently receiving conventional lines of treatment (steroids, IVIG, azathioprine, and rituximab, Mycophenolate mofetil) will continue on the same line of treatment | Drug | group 2 conventional Treatment |
Primary outcome
Expression of glycoprotein VI collagen receptor
Time frame: at 24 weeks
Percentages of patients achieving increased expression of glycoprotein VI collagen receptor
3 secondary outcomes
Complete response or response
Time frame: at 24 weeks
Maintenance of response
Time frame: at 24 weeks
Safety: Number of Patients who will have adverse events
Time frame: at 24 weeks
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 28 Oct 2021.
- Background: PubMed 17077333Mazzucconi MG, Fazi P, Bernasconi S, De Rossi G, Leone G, Gugliotta L, Vianelli N, Avvisati G, Rodeghiero F, Amendola A, Baronci C, Carbone C, Quattrin S, Fioritoni G, D'Alfonso G, Mandelli F; Gruppo Italiano Malattie EMatologiche dell'Adulto (GIMEMA) Thrombocytopenia Working Party. Therapy with high-dose dexamethasone (HD-DXM) in previously untreated patients affected by idiopathic thrombocytopenic purpura: a GIMEMA experience. Blood. 2007 Feb 15;109(4):1401-7. doi: 10.1182/blood-2005-12-015222. Epub 2006 Oct 31.
- Results publication: PubMed 2665875Buchanan GR. Overview of ITP treatment modalities in children. Blut. 1989 Jul;59(1):96-104. doi: 10.1007/BF00320257.
- Results publication: PubMed 26688484Bussel JB, de Miguel PG, Despotovic JM, Grainger JD, Sevilla J, Blanchette VS, Krishnamurti L, Connor P, David M, Boayue KB, Matthews DC, Lambert MP, Marcello LM, Iyengar M, Chan GW, Chagin KD, Theodore D, Bailey CK, Bakshi KK. Eltrombopag for the treatment of children with persistent and chronic immune thrombocytopenia (PETIT): a randomised, multicentre, placebo-controlled study. Lancet Haematol. 2015 Aug;2(8):e315-25. doi: 10.1016/S2352-3026(15)00114-3. Epub 2015 Jul 28.
- Results publication: PubMed 26477577Chiou TJ, Chang YF, Wang MC, Kao CW, Lin HY, Chen TY, Hsueh EJ, Lan YJ, Sung YC, Lin SF, Bai LY, Chen CG. Eltrombopag enhances platelet adhesion by upregulating the expression of glycoprotein VI in patients with chronic immune thrombocytopenic purpura. Transl Res. 2015 Dec;166(6):750-761.e4. doi: 10.1016/j.trsl.2015.09.005. Epub 2015 Sep 30.
- Results publication: PubMed 11919310Cines DB, Blanchette VS. Immune thrombocytopenic purpura. N Engl J Med. 2002 Mar 28;346(13):995-1008. doi: 10.1056/NEJMra010501. No abstract available.
- Results publication: PubMed 28627134Ehrlich LA, Kwitkowski VE, Reaman G, Ko CW, Nie L, Pazdur R, Farrell AT. U.S. Food and Drug Administration approval summary: Eltrombopag for the treatment of pediatric patients with chronic immune (idiopathic) thrombocytopenia. Pediatr Blood Cancer. 2017 Dec;64(12). doi: 10.1002/pbc.26657. Epub 2017 Jun 19.
- Results publication: PubMed 24674813Gardiner EE, Andrews RK. Platelet receptor expression and shedding: glycoprotein Ib-IX-V and glycoprotein VI. Transfus Med Rev. 2014 Apr;28(2):56-60. doi: 10.1016/j.tmrv.2014.03.001. Epub 2014 Mar 12.
- Results publication: PubMed 20148887Gardiner EE, Thom JY, Al-Tamimi M, Hughes A, Berndt MC, Andrews RK, Baker RI. Restored platelet function after romiplostim treatment in a patient with immune thrombocytopenic purpura. Br J Haematol. 2010 May;149(4):625-8. doi: 10.1111/j.1365-2141.2010.08092.x. Epub 2010 Feb 8. No abstract available.
- Results publication: PubMed 26231455Grainger JD, Locatelli F, Chotsampancharoen T, Donyush E, Pongtanakul B, Komvilaisak P, Sosothikul D, Drelichman G, Sirachainan N, Holzhauer S, Lebedev V, Lemons R, Pospisilova D, Ramenghi U, Bussel JB, Bakshi KK, Iyengar M, Chan GW, Chagin KD, Theodore D, Marcello LM, Bailey CK. Eltrombopag for children with chronic immune thrombocytopenia (PETIT2): a randomised, multicentre, placebo-controlled trial. Lancet. 2015 Oct 24;386(10004):1649-58. doi: 10.1016/S0140-6736(15)61107-2. Epub 2015 Jul 28.
- Results publication: PubMed 12359731Holmes ML, Bartle N, Eisbacher M, Chong BH. Cloning and analysis of the thrombopoietin-induced megakaryocyte-specific glycoprotein VI promoter and its regulation by GATA-1, Fli-1, and Sp1. J Biol Chem. 2002 Dec 13;277(50):48333-41. doi: 10.1074/jbc.M206127200. Epub 2002 Sep 30.
- Results publication: PubMed 17452226Klaassen RJ, Blanchette VS, Barnard D, Wakefield CD, Curtis C, Bradley CS, Neufeld EJ, Buchanan GR, Silva MP, Chan AK, Young NL. Validity, reliability, and responsiveness of a new measure of health-related quality of life in children with immune thrombocytopenic purpura: the Kids' ITP Tools. J Pediatr. 2007 May;150(5):510-5, 515.e1. doi: 10.1016/j.jpeds.2007.01.037.
- Results publication: PubMed 23361904Rodeghiero F, Michel M, Gernsheimer T, Ruggeri M, Blanchette V, Bussel JB, Cines DB, Cooper N, Godeau B, Greinacher A, Imbach P, Khellaf M, Klaassen RJ, Kuhne T, Liebman H, Mazzucconi MG, Newland A, Pabinger I, Tosetto A, Stasi R. Standardization of bleeding assessment in immune thrombocytopenia: report from the International Working Group. Blood. 2013 Apr 4;121(14):2596-606. doi: 10.1182/blood-2012-07-442392. Epub 2013 Jan 29.
- Individual participant dataSharing planned: Undecided. Still investigators did not decide about sharing individual participants data
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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.
Azza AG Tantawy, MD principal investigator
Ain shams university, Faculty of medicine, Pediatric Hematology &Oncology department
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Eltrombopag and conventional in people with Idiopathic Thrombocytopenic Purpura, run by Nayera Hazaa Elsherif at 1 site in Egypt.
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 4 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: finished, as of the sponsor's last update on 28 Oct 2021. 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 Egypt. 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?
Expression of glycoprotein VI collagen receptor (time frame: at 24 weeks). 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 NCT03412188, which also lists 15 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 28 Oct 2021.