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CTRI Number  CTRI/2025/07/090846 [Registered on: 14/07/2025] Trial Registered Prospectively
Last Modified On: 13/09/2025
Post Graduate Thesis  Yes 
Type of Trial  Interventional 
Type of Study   Drug 
Study Design  Randomized, Parallel Group Trial 
Public Title of Study   Efficacy of combination of IV Iron, Vitamin B12, Folic acid and erythropoietin to prevent anemia after bone tumour surgery. 
Scientific Title of Study   Multimodal Haematopoietic Intervention (IV Iron, Erythropoietin, Vitamin B12, Folic acid) for the prevention of postoperative anaemia in major orthopaedic tumour surgery: A Randomized Control Trial 
Trial Acronym  NIL 
Secondary IDs if Any  
Secondary ID  Identifier 
NIL  NIL 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Yogeshver A 
Designation  Junior Resident (Anaesthesiology) 
Affiliation  All India Institue of Medical Sciences (AIIMS), New Delhi 
Address  Department of Anaesthesiology, Pain Medicine and Critical Care, All India Institute of Medical Sciences, New Delhi.

New Delhi
DELHI
110029
India 
Phone  9629017061  
Fax    
Email  yogeshverarivazhagan1706@gmail.com  
 
Details of Contact Person
Scientific Query
 
Name  Rakesh Kumar 
Designation  Additinal Professor 
Affiliation  All India Institue of Medical Sciences (AIIMS), New Delhi 
Address  Department of Anaesthesiology, Pain Medicine and Critical Care, Room no. 5007, 5th floor, Main Block, All India Institute of Medical Sciences, New Delhi.

New Delhi
DELHI
110029
India 
Phone  7838043581  
Fax    
Email  drrakesh.kumar.akb@gmail.com  
 
Details of Contact Person
Public Query
 
Name  Rakesh Kumar 
Designation  Additinal Professor 
Affiliation  All India Institue of Medical Sciences (AIIMS), New Delhi 
Address  Department of Anaesthesiology, Pain Medicine and Critical Care, Room no. 5007, 5th floor, Main Block, All India Institute of Medical Sciences, New Delhi.

New Delhi
DELHI
110029
India 
Phone  7838043581  
Fax    
Email  drrakesh.kumar.akb@gmail.com  
 
Source of Monetary or Material Support  
All India Institute of Medical Sciences (AIIMS), Ansari Nagar East, New Delhi-110029. Delhi, India. 
 
Primary Sponsor  
Name  All India Institute of Medical Sciences (AIIMS), New Delhi 
Address  Ansari Nagar East, New Delhi- 110029. 
Type of Sponsor  Research institution and hospital 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     India  
Sites of Study  
No of Sites = 1  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
DrYogeshver A  All India Institute of Medical Sciences (AIIMS) New Delhi.  ICU/HDU/Recovery room Department of Anaesthesiology, Pain Medicine and Critical Care, AIIMS New Delhi- 110029.
New Delhi
DELHI 
9629017061

yogeshverarivazhagan1706@gmail.com 
 
Details of Ethics Committee  
No of Ethics Committees= 1  
Name of Committee  Approval Status 
Institute Ethics Committee, AIIMS New Delhi.  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Not Applicable 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  (1) ICD-10 Condition: C40-C41||Malignant neoplasms of bone and articular cartilage,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Intervention  Multimodal haeamtopoietic bundle (parenteral plus oral)  1. IV Ferric derisomaltose 1.0gram or 20 mg per kg in 100mL NS over one hour. 2. Vitamin B12 ( Methylcobalamine) 500mcg in 100mL NS over 30 mins. 3. Subcutaneous Erythropoietin 40000 IU 4. Oral Vitamin B12 and folic acid 5mg once daily for 28 days after normalisation of bowel habit.  
Comparator Agent  Standard institute protocol.  Oral iron and folate tablets for 28 days, after bowel habits come back to normal. 
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  80.00 Year(s)
Gender  Both 
Details  1. Patients above or at 18 years of age.
2. Underwent major orthopaedic malignancy surgery with predicted intraoperative blood loss of 2 litres or more than or more than or equal to 40 percentage of blood volume.
3. Intraoperative blood transfusion of more than or equal to 4 units of PRBC.
4. Post-operative day 1 (POD-1) haemoglobin in moderate anaemia range (8-11 grams per dL).
5. Provision of written informed consent
 
 
ExclusionCriteria 
Details  1. The patient refused to participate in the study.
2. Patients with known haematological disorders (thalassemia, sickle cell disease, myelodysplastic syndromes).
3. Patients known to have a hypersensitivity reaction to intravenous iron, erythropoietin, vitamin B12 and folic acid)
4. Patients with chronic kidney disease require dialysis.
5. Pregnant female and breastfeeding mothers.
6. Patients with uncontrolled hypertension.
7. Patients with severe liver dysfunction (Child-Pugh grade C).
8. Ongoing infection or sepsis.
9. Patients previously on long-term iron or erythropoietin treatment.
10. Patients with seizure disorders on anti-epileptic drugs.
 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Sequentially numbered, sealed, opaque envelopes 
Blinding/Masking   Open Label 
Primary Outcome  
Outcome  TimePoints 
1. Comparison of hemoglobin levels in the postoperative period between both the groups.  Postoperative days 1, 7 and 28. 
 
Secondary Outcome  
Outcome  TimePoints 
1. Identify the number of patients who remain anemic on 28th day postoperative as per WHO criteria of anemia.
2. Comparing the RBC indices (MCV, MCH, MCHC and RDW) on POD 7 and 28 in both the patient groups.
3. Comparing the reticulocyte counts on preoperative and POD 7 (or before discharge whichever is earlier)
4. Record the iron profile changes (serum iron, ferritin, transferrin saturation and TIBG) on POD 0 and 28.
5. To assess the safety and tolerability of intravenous iron formulation in patients.
6. To assess the safety of erythropoietin in patients.
7. Compare the length of hospital stay between both the groups.
8. Presence of any post-operative surgical site infections in both the groups.
 
Postoperative days 1, 7 and 28. 
 
Target Sample Size   Total Sample Size="110"
Sample Size from India="110" 
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" 
Phase of Trial   N/A 
Date of First Enrollment (India)   30/07/2025 
Date of Study Completion (India) Applicable only for Completed/Terminated trials 
Date of First Enrollment (Global)  Date Missing 
Date of Study Completion (Global) Applicable only for Completed/Terminated trials 
Estimated Duration of Trial   Years="1"
Months="6"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  
Not Applicable 
Recruitment Status of Trial (India)  Open to Recruitment 
Publication Details   N/A 
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Response - NO
Brief Summary  

Postoperative anaemia is a common and significant complication following major orthopaedic oncologic surgeries. The prevalence of postoperative anaemia in orthopaedic tumour surgeries is as high as 89.2%. Major reasons include high vascularity of the region, difficult-to-do preoperative blood control measures, including arterial embolization, extensive resection, difficulty in application of tourniquet during the intraoperative period due to the location of the surgery. As a part of  patient blood management protocol, blood transfusion is restricted to conditions when the haemoglobin falls below 8 grams per decilitres in orthopaedic surgery. Postoperative anaemia may lead to various other complications like increased surgical site infection, sepsis, increased in-hospital stay, delayed wound healing and even may need ICU admissions

According to the WHO, postoperative anaemia could be classified 

Mild (haemoglobin 11.0–11.9gm/dl in women and 11.0 – 12.9gm/dl in male)

Moderate (haemoglobin 8.0–10.9gm/dl) and 

severe (haemoglobin < 8.0gm/dl) 

Postoperative anaemia may be due to a restrictive intraoperative blood transfusion strategy, significant intraoperative blood loss, reduced erythropoiesis due to a generalized release of inflammatory mediators in the postoperative period, inadequate oral intake, and poor absorption of oral iron preparation. Iron is an essential component of erythropoiesis, and its absorption decreases significantly postoperatively from the gastrointestinal tract due to increased hepcidin secretion. Hepcidin is a positive acute-phase reactant that decreases iron absorption, transport, and release. These patients also have other nutritional deficiencies, such as vitamin B12 and folic acid, due to a generalized malnutrition state resulting from the malignancy and the chemotherapy.

The treatment of postoperative anaemia depends on either blood transfusions, oral use of haematinics (iron, folic acid, and vitamin B12), or parenteral iron, vitamin B12, and an erythropoietic stimulant in the form of subcutaneous erythropoietin. Blood transfusions increase haemoglobin (Hb) levels only transiently and come at the risk of blood transfusion-related reactions, infections, and cost. 

In the perioperative period, patient blood management (PBM) strategies are developed for perioperative blood transfusion. Treatment or prevention of the preoperative anaemia is the mainstay of PBM. PBM mainly relies on three pillars: 1. Identifying and managing anaemia before surgery 2. Minimizing blood loss during the perioperative period 3. Supporting the patient’s individual ability to tolerate anaemia, like the use of more conservative transfusion thresholds. The first pillar of PBM is most effective but difficult to implement in malignancy surgery due to time sensitive nature of surgery. Also, the use of a lower Hb cut-off as a transfusion trigger implies that a certain degree of postoperative anaemia is accepted. Though blood transfusions are considered the mainstay treatment for the correction of perioperative anaemia, they are mainly considered for patients in the severe anaemia category( Hemoglobulin less than 8gm/dl). For the prevention of postoperative anaemia, the standard of care practised in our institution and most other institutions is oral iron and folic acid combination supplementation in the postoperative period once the patient takes it orally and their bowel habit normalizes. However, many patients may not comply with the oral formulation for several reasons. Common reasons include poor bioavailability of the drug due to inflammation and drug interaction with food; its metallic taste; constipation, and other side effects. Hence, parenteral iron will counteract the difficulties associated with oral tablets. Due to postoperative inflammation, the effect of erythropoietin also diminishes. This effect will be supplemented with one dose of erythropoietin on postoperative day one. A single erythropoietin dose also inhibits hepcidin synthesis and will help in the erythropoiesis process. Poor postoperative intake and preoperative clinical or subclinical deficiency of vitamin B12 and folic acid will be taken care of by postoperative vitamin B12 and folic acid supplementation.   

So, we hypothesized that a single dose of multimodal bundle of hematinic (intravenous iron, intravenous vitamin B12, subcutaneous erythropoietin alpha) may help improve hemoglobin levels in patients with moderate postoperative anemia (hemoglobin concentration 8-11 g/dL) after major orthopedic tumor surgery with a significant intraoperative blood loss.

 
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