| 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
|
|
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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
|
|
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Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: C40-C41||Malignant neoplasms of bone and articular cartilage, |
|
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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.
|
|
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Method of Generating Random Sequence
|
Computer generated randomization |
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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. |