"The Safety and Efficacy of Mini-Pool IVIG Initiation and Maintenance Therapy for Management of Children With Persistent ITP, A Novel Approach for LMICs"
Phase: NA
Conditions: Persistent Immune Thrombocytopenia
Sponsor: Assiut University

Cover Page 
 
Official Title of the study 
 
The Safety and Efficacy of Mini-Pool IVIG as Loading and Maintenance Therapy for 
Children with Persistent Immune Thrombocytopenia: A Novel Approach for Low-Middle 
Income Countries 
NCT Number: 
                                 Not yet assigned 
Document Date:     
                                July 2025 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
The Safety and Efficacy of Mini-Pool IVIG as Loading and Maintenance Therapy for Children 
with Persistent Immune Thrombocytopenia, A Novel Approach for Low-Middle income 
countries  
 
Introduction: 
Immune thrombocytopenia (ITP) occurs with an incidence rate of 1.6 to 3.9 per 100,000 
patient-years, which increases with age and has a slight female preponderance [1] 
It is an autoimmune disease characterized by an isolated decrease in the platelet count and an 
increased risk of bleeding. The pathogenesis is complex, affecting multiple components of the 
immune system and causing both peripheral destruction of platelets and impaired 
megakaryopoiesis in bone marrow. The diagnosis is typically made by excluding known 
thrombocytopenia causes. ITP can affect both children and adults. The American Society of 
Hematology (ASH) defines ITP as a generalized purpuric rash accompanied by a platelet count 
less than 100,000/μL and normal white blood cell (WBC) count and hemoglobin level.  Primary 
ITP may be further categorized based on the timing and persistence of symptoms. Newly 
diagnosed ITP refers to the condition from the time of diagnosis to 3 months afterward. 
Persistent ITP arises when symptoms continue 3 to 12 months following the initial diagnosis. 
Chronic ITP indicates ongoing symptoms beyond 12 months from the initial diagnosis until 
resolution or further management. Refractory ITP includes cases that do not resolve with 
splenectomy,   Severe thrombocytopenia, when platelet counts are below 20,000/μL, warrants 
medical treatment [2].  
 
Management strategies have evolved significantly, emphasizing individualized treatment 
approaches based on disease severity, bleeding risk, and patient-specific factors. The latest 
therapeutic options, ranging from observation and first-line treatments such as corticosteroids 
and intravenous immunoglobulin (IVIG) to second-line therapies, including thrombopoietin 
receptor agonists and immunosuppressive agents.  
 

The balancing of treatment efficacy with the potential side effects and long-term outcomes is 
very crucial for optimum management. There is  emerging role of personalized medicine in 
optimizing care for children with ITP, highlighting recent advances in targeted therapies and the 
potential for future research to refine diagnostic and treatment paradigms [3].  
Eltrombopag (ELT) is effective and safe in adult persistent/chronic immune thrombocytopenia 
(p/cITP); a proportion could achieve a sustained response off treatment (SRoT).  A multicentre 
retrospective observational study was performed in November 2022 for children with p/cITP 
who used ELT alone for >2 months between January 2017 and November 2021. Clinical data of 
pre-, during and post-ELT were collected. SRoT was defined as maintaining a platelet count of 
≥30 × 10(9) /L without rescue therapy for at least 6 months off ELT. There were 43.3% and 
25.9% achieved complete response (CR) and response (R). [4]. 
 
While IVIG is considered as safe and effective first line therapy for management of acute 
pediatric/adult ITP [5], yet there is no report on the role of IVIG as second line therapy for 
persistent/chronic ITP. One of the reasons might be the high cost of IVIG therapy compared to 
other standard therapies. El Ekiaby et al published a method for preparation of IVIG from mini-
pools of plasma in blood bank environment using disposable medical devices produced by Swiss 
Company VIPS. The devices combine single use disposable bags and validated virus inactivation 
and IgG purification chemicals [6]. Mini-pool immunoglobulins proved safety and efficacy for 
management of acute pediatric ITP in a prospective randomized clinical trial [7]. The use of this 
new technology significantly reduces the cost of production of local mini-pool IVIG 
preparations. The use of locally produced mini-pool IVIG might be a safe and cost effective 
second line therapy. 
 
Aim of the study: 
Assessment of safety and efficacy of mini-pool IVIG as a second line therapy for management of 
pediatric persistent ITP.  
 
Primary end points:  
1-Bleeding score, duration, site and frequency calculated as BAT score 
2-Frequency of hospital admission due to ITP critical bleeding episodes excluding hospital 
admission for Mini-Pool IVIG administration 
3-Levels of platelet count during study period and its maintenance during subsequent 6 months 
after end of study period for patients with PC >30,000/uL  
 
Secondary end points: 
1-Record of adverse events 
2-Patient/family satisfaction 
3-School attendance and physical activity 
4- Presence of a sustained response 
 
Study protocol: 
Three tertiary care Pediatric Hematology/Oncology centers will be enrolling children with 
persistent ITP “loss of initial response to first line therapy (steroids/IVIG) within 3-6 months” 

Participating centers are, Ain Shams, Zagazig and Assuit Pediatric Hematology/Oncology 
 
Inclusion Criteria: 
-Age 1 – 10 years  
-Gender: Males and Females 
-Persistent ITP according to ASH definition  
-No history of treatment with thrombopoietin agonists  
 
Exclusion criteria:  
-History of severe drug adverse events to IVIG 
-Previous history of ICH 
-Difficult venous access 
-Congenital thrombocytopenia, secondary ITP and non-immune thrombocytopenia  
 
Sample size  
20 child with persistent ITP  
 
6-Study period 3 – 6 months followed by 6 months observation for cases that showed remission 
off-therapy ( SRoT >100,000, RoT >30,000 with no bleeding manifestations necessitating 
platelet enhancing therapy) after the end of the mini-pool IVIG therapy, 
 
7-Study protocol highlights: 
Infusion of 1 gm/kg of mini-pool IVIG as a loading dose over 6-8 hours, then repeat every 2-4 
weeks as a maintenance dose of 0.5 gm/KG every 2 – 4 weeks according to platelet count at 
end of 2nd week for 5 subsequent doses 
-Age at diagnosis, sex, family history of bleeding  
-History of infection or vaccination before thrombocytopenia, onset of bleed acute or insidious 
onset 
- Initial blood count at onset of the diagnosis, at enrollment and before IVIG infusion and 72 
hours after end of IVIG infusion  
-Repeat CBC: 
 
-Platelet Count Below 50,000/µl repeat CBC weekly 
            - Platelet Count Above 50,000/µl repeat CBC every 2 weeks 
- 
-Record the following: 
 
-Platelet count 72 hours after infusion, after 2 weeks and just before subsequent 
maintenance dose 
 
-Infusion related adverse events 
 
-Frequency and site of bleeding episodes according to BAT scoring 
 
-Need for hospitalization 
 
-School attendance 
 
-Physical activities 
 
-Early study termination: 

 
-Severe adverse events 
 
-Non-compliance (missing 2 consecutive visits) 
 
-No improvement in platelet count after 3 infusions (< doubling basal pc or PC 
<30,000/mm3) 
 
Quality of response 
CR: platelet count ≥ 100 × 109/L and absence of bleeding 
 
R: platelet count ≥ 30 × 109/L and at least 2-fold increase the baseline count and absence of 
bleeding 
 
Time to response: time from starting treatment to time of achievement of CR or R 
 
NR: platelet count < 30 × 109/L or less than 2-fold increase of baseline platelet count or 
bleeding 
 
Loss of CR or R: platelet count below 100 × 109/L or bleeding (from CR) or below 30 × 109/L or 
less than 2-fold increase of baseline platelet count or bleeding (from R) 
 
Timing of assessment of response to IVIG: monthly for 6 months, bleeding and CBC 
Duration of response 
 
- 
Measured from the achievement of CR or R to loss of CR or R 
- 
Measured as the proportion of the cumulative time spent in CR or R during the period 
under examination as well as the total time observed from which the proportion is 
derived [8] 
 
 
References: 
 
1. 
Kohli, R. and S. Chaturvedi, Epidemiology and Clinical Manifestations of Immune 
Thrombocytopenia. Hamostaseologie, 2019. 39(3): p. 238-249. 
2. 
Pietras, N.M., et al., Immune Thrombocytopenia, in StatPearls. 2024, StatPearls 
Publishing Copyright © 2024, StatPearls Publishing LLC.: Treasure Island (FL). 
3. 
Thakur, Y., R.J. Meshram, and A. Taksande, Diagnosis and Management of Immune 
Thrombocytopenia in Paediatrics: A Comprehensive Review. Cureus, 2024. 16(9): p. 
e69635. 
4. 
Wang, Z., et al., Sustained response off treatment in eltrombopag for children with 
persistent/chronic primary immune thrombocytopenia: A multicentre observational 
retrospective study in China. Br J Haematol, 2023. 202(2): p. 422-428. 
5. 
Gotesman, M., et al., Pediatric Immune Thrombocytopenia. Adv Pediatr, 2024. 71(1): p. 
229-240. 

6. 
El-Ekiaby, M., et al., Minipool caprylic acid fractionation of plasma using disposable 
equipment: a practical method to enhance immunoglobulin supply in developing 
countries. PLoS Negl Trop Dis, 2015. 9(2): p. e0003501. 
7. 
Elalfy, M., et al., A randomized multicenter study: safety and efficacy of mini-pool 
intravenous immunoglobulin versus standard immunoglobulin in children aged 1-18 
years with immune thrombocytopenia. Transfusion, 2017. 57(12): p. 3019-3025. 
8. 
Rodeghiero, F., et al., Standardization of terminology, definitions and outcome criteria in 
immune thrombocytopenic purpura of adults and children: report from an international 
working group. Blood, 2009. 113(11): p. 2386-93.