Clinical trial NCT06531018: Role of Eltrombopag as First Line Therapy in Primary Immune Thrombocytopenia.
Official title: Efficacy of Eltrombopag & Prednisolone Versus Prednisolone Monotherapy in Newly Diagnosed Immune Thrombocytopenia- A Randomized Control Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Primary Immune Thrombocytopenia
Keywords: Primary ITP
Eltrombopag
First-line Therapy
Lead sponsor: Renata PLC
Sponsor class: INDUSTRY
First posted: 2024-07-31
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This will be a double-blind, placebo-control, randomized clinical trial conducted in the Department of Hematology, DMCH for one year. This study will help to establish the role of eltrombopag as a first-line therapy in newly diagnosed ITP. Newly diagnosed ITP patients will be selected after meeting inclusion and exclusion criteria, they will be thoroughly informed about the study, used drugs, randomization, risks, benefits, and follow-up. If they agree to participate, their consent will be taken and they will be enrolled in the study. A detailed history and clinical exam will be done. Primary investigation will be - CBC PBF, RBS, ANA, TSH, Anti H. pyloriIgG, Anti-HCV, APTT, and BMS (if indicated). The main outcome variable will be platelet count and number of spontaneous bleeding. Total sample size would be 100 (50 in each group). Enrolled patients would be divided into two groups (1:1) by block randomization. One group will get Eltrombopag\& Prednisolone and other group will get Eltrombopag\& Placebo. Researchers or any one related to the study in DMCH, patients \& their attendants, no one will know which patient will get placebo or eltrombopag. Only a respectable third party will know the information. A patient would be followed up on 1st, 2nd and 4th week of starting therapy. Patients would be evaluated in every follow up by history, physical examination and investigation. History of any spontaneous bleeding event, any discomfort or new symptoms science last follow up will be noted. General examination will be performed in every follow-up. CBC, RBS, ALT, AST, creatinine will be done in every follow-up. Data will be collected on a pre-designed case record form and will be collected through face-to-face interviews, physical examination, and laboratory reports. After data collection data will be edited, cleaned, and prepared for analysis at the end of the study. The statistical analysis will be conducted using SPSS version 25 statistical software. The results of the study will be published in national and international journals.

Detailed description: Study procedure After meeting inclusion and exclusion criteria patients will be thoroughly informed about the study, used drugs, randomization, risk and benefits, follow up. If they agree to participate in the study, their consent for this study will be taken and they will be enrolled in the study.

Detail history and clinical exam will be done. Key points are- History of spontaneous bleeding in last month, History of vaccination, History of recent viral infection, fever, Presence of organomegaly.

Primary investigation will be- CBC PBF, RBS, ANA, TSH, Anti H. pyloriIgG, Anti-HCV, APTT, BMS (if indicated)

NB:

1. If APTT is more than 10 sec of control, patient would be evaluated for Anti-Phospholipid Syndrome by anti-cardiolipin Antibody and Anti-beta2 glycoprotein1 Antibody
2. If Hemoglobin in less than 11.5gm/dL patient would be evaluated for Anemia by Iron Profile or Coomb's Test based on CBC parameter and PBF findings\] Randomization: Enrolled patients would be divided into two groups (1:1) by block randomization. Block Randomization would be done by computer generated pattern. Actual randomization plan will be provided by Renata limited team who know about eltrombopag and placebo. Randomization allocation delivered only to the enrolling site study staff. A voluntary nurse will be in charge of enrolling the patients according to randomization plan.

Blinding and placebo control: It will be a double-blind study. Researchers nor participants will know who is getting placebo/eltromopag. One group will get Prednisolone \& Eltrombopag and another group will get Prednisolone \& Placebo. Eltrombopag, Prednisolone and Placebo will be provided by Renata Limited Bangladesh and patient will get at free of costs. Placebo will have same size, shape, color, markings, taste, smell and packaging like Eltrombopag. Eltrombopag and placebo will be provided in separate color-coded box marked-A (red) or B (green). Group A and Group B participants will be given colored cards (red and green) for identification. They will receive tablets from marked box. Researchers or any one related to the study in DMCH, patients \& their attendants no will know which box contain placebo or eltrombopag. Only respectable person of Renata limited will know the information. The team who knows the information will be head by their CEO. At the end point all data will be submitted to the team who know about placebo.

Experimental Group - Eltrombopag\& Prednisolone Control Group - Prednisolone and Placebo Dose- Prednisolone 1mg/kg/day for 28 days Eltrombopag/Placebo 25mg/day for 28 days Follow Up- Follow up at the end of 1st week, 2nd week and 4th week Patient would be evaluated in every follow up by history, physical examination and investigation. History of any spontaneous bleeding event, any discomfort or new symptoms science last follow up. General examination will be performed in every follow up. CBC, RBS, ALT, AST and creatinine will be done in every follow up.

Primary End Point-28 days after starting therapy. Complete Response is expected after 28 days of therapy.

Patient would continue therapy and follow up in OPD but would not be included in the study.

Supportive care and rescue- A Data and Safety Monitoring Board (DSMB) will be formed which will include two members of NREC, one hematologist and one medicine specialist. Any adverse event (Drugs side effects- headache, weight gain, changes in liver enzymes, high blood sugar) or serious adverse event (grade 3 or grade 4 bleeding, hospitalization, thrombosis) will be delt with proper medical care.

If any patient shows no response within 14 days and has grade 3 or 4 bleeding rescue with methyl prednisolone or IV Ig would be given and discontinued from study. If group A patient reaches platelet count \>400x109\\L, eltrombopag will be stopped.

Data Analysis After data collection data will be edited, cleaned and prepared for analysis at the end of the study. At the end of the study, all data will be submitted to the team who know about placebo/eltrombopag. The statistical analysis will be conducted using SPSS (statistical package for the social science) version 25 statistical software. The findings of the study will be presented by frequency and percentage in tables. Means and standard deviations for continuous variables and proportion for categorical variables will be used to describe the characteristics of the total sample. Association between two qualitative variables will be assessed by Chi-square test, where p\<0.05 with 95% confidence level will be considered as significant. Appropriate statistical tests will be done to interpret the findings of the study.

Eligibility criteria: Inclusion Criteria:

1. Patients with newly diagnosed ITP
2. Platelet Count ≤ 30x109/L
3. Age between 18 to 70 years.

Exclusion Criteria:

1. Persistent or chronic ITP
2. Pregnant women
3. Secondary ITP- ITP due to SLE, Anti-phospholipid syndrome, Evans syndrome, HCV or H Pylori associated ITP.
4. History of vaccination, recent viral infection, fever
5. Evan's Syndrome
6. Known case of chronic renal failure or liver diseases
7. Grade 3 or 4 bleeding at presentation.

Primary outcomes:
measure: Changes in Platelet count
timeFrame: 28 days (platelet count will be measured at the end of 1st, 2nd and 4th week)
measure: Spontaneous bleeding
timeFrame: 28 days (Spontaneous bleeding episodes will be noted by face to face interview at the end of 1st, 2nd and 4th week)
Secondary outcomes:
measure: Changes in hemoglobin
timeFrame: 28 days (hemoglobin will be measured at the end of 1st, 2nd and 4th week)
measure: Changes in Total WBC count
timeFrame: 28days (WBC count will be measured at the end of 1st, 2nd and 4th week)
measure: Change in ALT
timeFrame: 28 days ( ALT will be measured at the end of 1st, 2nd and 4th week)
measure: Change in AST
timeFrame: 28 days ( AST will be measured at the end of 1st, 2nd and 4th week)
measure: Change in S.Createnine
timeFrame: 28 days (S.Createnine will be measured at the end of 1st, 2nd and 4th week)
measure: Change in RBS
timeFrame: 28 days (RBS will be measured at the end of 1st, 2nd and 4th week)
Other outcomes:
Locations:
city: Dhaka
country: Bangladesh
facility: Dhaka Medical College Hospital
Study officials:
affiliation: Dhaka Medical College
name: Md Manirul Islam, MBBS,FCPS
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gomez-Almaguer D, Herrera-Rojas MA, Jaime-Perez JC, Gomez-De Leon A, Cantu-Rodriguez OG, Gutierrez-Aguirre CH, Tarin-Arzaga L, Hernandez-Reyes J, Ruiz-Arguelles GJ. Eltrombopag and high-dose dexamethasone as frontline treatment of newly diagnosed immune thrombocytopenia in adults. Blood. 2014 Jun 19;123(25):3906-8. doi: 10.1182/blood-2014-01-549360. Epub 2014 May 6.
citation: Gomez-Almaguer D, Colunga-Pedraza PR, Gomez-De Leon A, Gutierrez-Aguirre CH, Cantu-Rodriguez OG, Jaime-Perez JC. Eltrombopag, low-dose rituximab, and dexamethasone combination as frontline treatment of newly diagnosed immune thrombocytopaenia. Br J Haematol. 2019 Jan;184(2):288-290. doi: 10.1111/bjh.15070. Epub 2017 Dec 21. No abstract available.
citation: Gomez-Almaguer D. Eltrombopag-based combination treatment for immune thrombocytopenia. Ther Adv Hematol. 2018 Oct 4;9(10):309-317. doi: 10.1177/2040620718798798. eCollection 2018 Oct.
citation: Provan D, Stasi R, Newland AC, Blanchette VS, Bolton-Maggs P, Bussel JB, Chong BH, Cines DB, Gernsheimer TB, Godeau B, Grainger J, Greer I, Hunt BJ, Imbach PA, Lyons G, McMillan R, Rodeghiero F, Sanz MA, Tarantino M, Watson S, Young J, Kuter DJ. International consensus report on the investigation and management of primary immune thrombocytopenia. Blood. 2010 Jan 14;115(2):168-86. doi: 10.1182/blood-2009-06-225565. Epub 2009 Oct 21.
citation: Shimano KA, Grace RF, Despotovic JM, Neufeld EJ, Klaassen RJ, Bennett CM, Ma C, London WB, Neunert C. Phase 3 randomised trial of eltrombopag versus standard first-line pharmacological management for newly diagnosed immune thrombocytopaenia (ITP) in children: study protocol. BMJ Open. 2021 Aug 27;11(8):e044885. doi: 10.1136/bmjopen-2020-044885.