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Preoperative anemia is common worldwide, ranging from 25% in knee arthroplasties to 60% in colorectal malignancies. In Singapore, about a quarter (27%) of all patients have anaemia prior to operation at a main tertiary center. Currently, the rate of preoperative anemia in Singapore General Hospital (SGH) is 26.6%.
This is an alarming public health issue as the negative impact of preoperative anemia on post-surgical outcomes has been well documented and include increased rates of perioperative blood transfusion, mortality, adverse cardiac and non-cardiac complications including pulmonary complications, wound infections, systemic sepsis and venous thromboembolism, as well as prolonged length of hospital stay and increased healthcare costs. These data suggest that reducing preoperative anemia prior to major surgery is imperative to improve clinical outcomes and decrease healthcare costs.
This study responds to an urgent need to optimize the current standard practice for managing preoperative anemia. It is designed as a randomised, open-label, study to investigate the efficacy of intravenous iron compared to oral iron in patients with anemia undergoing major surgery to reduce surgical complications. To demonstrate the feasibility of conducting such trial in a larger scale, a pilot study with the same design will be conducted. The findings of this pilot study will also inform the study design and sample size for the larger study.
If successful, the results will inform clinical practice guidelines, result in better patient and clinical outcomes, reduce burden on the health care system, and change health-related policy. For example, all forms of intravenous iron therapy are currently not subsidized by the Singapore government which is in stark contrast with allogenic blood transfusion, which is subsidised and readily available at a substantially reduced rate to patients. Hence, it will cost the patients more out of pocket to be treated with intravenous iron than to have allogenic blood transfusion. Incorporating a preoperative anemia correction protocol in the current surgical pathway is a potential strategy to combat healthcare cost inflation and the increasing demand for blood products.
Full description
Preoperative anemia is common worldwide, ranging from 25% in knee arthroplasties to 60% in colorectal malignancies. In Singapore, about a quarter (27%) of all patients have anaemia prior to operation at a main tertiary center. Currently, the rate of preoperative anemia in Singapore General Hospital (SGH) is 26.6%.
This is an alarming public health issue as the negative impact of preoperative anemia on post-surgical outcomes has been well documented and include increased rates of perioperative blood transfusion, mortality, adverse cardiac and non-cardiac complications including pulmonary complications, wound infections, systemic sepsis and venous thromboembolism, as well as prolonged length of hospital stay and increased healthcare costs. These data suggest that reducing preoperative anemia prior to major surgery is imperative to improve clinical outcomes and decrease healthcare costs.
This study responds to an urgent need to optimize the current standard practice for managing preoperative anemia. It is designed as an open-label, parallel design pilot randomised control trial to determine the feasibility of conducting a larger scale study powered to investigate reduction in complication rate. There will be two arms, intervention (IV FCM 15mg/kg, up to 1000 mg) and usual care (Ferrous fumarate 200mg twice daily). All participants will be followed for three months from date of operation.
60 participants will be randomly allocated in a 1:1 ratio to either preoperative FCM (intervention) or oral iron (standard care). Participants are stratified to surgical type (upper or lower intestinal surgeries) and surgical approach (laparoscopic or open). The sample size was selected based on the observation that at least 12 participants per group provide adequate measurement precision and power to detect associations. The study aims to balance 15 participants per stratum to account for dropouts and loss to follow up.
Written informed consent will be obtained prior to enrolment in the study. Study data will be entered into a secure data management system and retained for up to 6 years after the study ends, as per institutional guideline. There will be no procedures recorded on electronic media.
The dosing for FCM is based on the maximum dose of intravenous iron that can be safely given in a reasonable time period. The selected dose for the study corresponds with the manufacturer's recommended IV FCM dose for iron repletion in iron deficiency anemia. (Approved product label attached as annex). This dose of 15mg/kg or up to 1000 mg was also the dose used in other similar trials, hence facilitating comparison of results across study populations. As with the manufacturer's recommendation, the drug will be diluted in 250 ml Normal Saline and given over 30 minutes with the patient closely observed for signs and symptoms of hypersensitivity reactions during and for at least 30 minutes following each injection. If contraindication to IV FCM develops, treatment will be stopped and usual care commenced. Such reactions will be recorded and analyzed as an adverse event. The surgeon will be informed of the patient's participation in the study.
The dosing for oral iron would be as per current clinical protocol, which is ferrous fumarate 200mg twice daily.
To determine the effectiveness of a single preoperative dose of IV FCM, compared to oral iron therapy for treating iron deficiency anemia prior to major abdominal surgery, in reducing perioperative blood transfusion requirement and 30-day incidence of postoperative complications. Other secondary objectives:
Reporting of adverse events involves the PI submitting to the approving CIRB the completed SAE Reporting Form within the stipulated timeframe. PI is responsible for informing the institution representative (local SAE resulting in death), sponsor or regulatory bodies as required and appropriate.
Reporting timeline to CIRB:
All SAEs that are unexpected and related to the study drug will be reported to HSA. All SAEs will be reported to HSA according to the HSA Guidance for Industry "Safety Reporting Requirements for Clinical Drug Trials." The investigator is responsible for informing HSA no later than 15 calendar days after first knowledge that the case qualifies for expedited reporting. Follow-up information will be actively sought and submitted as it becomes available. For fatal or life-threatening cases, HSA will be notified as soon as possible but no later than 7 calendar days after first knowledge that a case qualifies, followed by a complete report within 8 additional calendar days.
The data and safety monitoring will be performed by the Principal Investigator and Co-Investigators, and subjected to audit and monitoring of the practices by Division of Research, SGH as well as CIRB.
The following precautions are in place:
All data will be monitored and reviewed by the PI or Co-investigators. Training will be given to the research coordinator and entry of data from the case report forms for analysis will be verified by a second person from the study team.
Data will be entered on paper, prior to being de-identified and entered electronically for analysis. Existing perioperative surgical, ICU and hospital data will be used to capture patient demographics, procedure urgency, intraoperative procedure and anaesthetic variables, blood product utilisation, mechanical ventilation, delirium/coma, ICU and hospital LOS and major adverse events. Local research staff will enter de-identified study data onto a trial-specific electronic case report form.
Hard copy of research data will be kept in a locked cabinet within the staff-only area of Preoperative Assessment Center, Block 3 Level 1, SGH. Soft copy of all data will be kept on a password protected PC within the hospital's secure network, which is located in the same staff-only area. All data will be de-identified. The participants will not have their NRIC and names displayed in the data. Instead a code will be assigned to each participant to protect the confidentiality of the research data. The key to the code will be kept in a separate access controlled, staff-only office within the department of anesthesiology, SGH. The PI will have access to the identifiers.
For aim 1, the intervention would be deemed feasible if the following three objectives were achieved:
The investigator(s)/institution(s) will permit study-related monitoring, audits and/or IRB review and regulatory inspection(s), providing direct access to source data/document.
All data will be monitored and reviewed by the PI or Co-investigators. Training will be given to the research coordinator and entry of data from the case report forms for analysis will be verified by a second person from the study team.
If successful, the results will inform clinical practice guidelines, result in better patient and clinical outcomes, reduce burden on the health care system, and change health-related policy. For example, all forms of intravenous iron therapy are currently not subsidized by the Singapore government which is in stark contrast with allogenic blood transfusion, which is subsidised and readily available at a substantially reduced rate to participants. Hence, it will cost the participants more out of pocket to be treated with intravenous iron than to have allogenic blood transfusion. Incorporating a preoperative anemia correction protocol in the current surgical pathway is a potential strategy to combat healthcare cost inflation and the increasing demand for blood products.
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60 participants in 2 patient groups
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Thiri Naing Thin; Hairil Rizal Abdullah
Data sourced from clinicaltrials.gov
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