Ferric derisomaltose and Outcomes in the Recovery of Gynecologic oncology: ERAS (Enhanced Recovery After Surgery) (FORGE) – a protocol for a pilot randomised double-blinded parallel-group placebo-controlled study of the feasibility and efficacy of intravenous ferric derisomaltose to correct preoperative iron-deficiency anaemia in patients undergoing gynaecological oncology surgery

Abstract

Introduction

Iron-deficiency anaemia is common in gynaecological oncology patients. Blood transfusions are immunosuppressive and carry immediate and long-term risks. Oral iron replacement remains the standard of care but requires prolonged treatment courses associated with gastrointestinal side effects, poor compliance and variable absorption in cancer patients. Intravenous iron has been shown to decrease the need for allogeneic blood transfusion in gynaecological oncology patients undergoing chemotherapy, but the efficacy of this treatment in the preoperative period is unknown. The goal of this pilot study is to determine the effect of intravenous ferric derisomaltose on preoperative haemoglobin in patients undergoing surgery for gynaecological malignancy.

Methods and analysis

We will conduct a pilot single-centre, parallel-arm randomised controlled trial of intravenous ferric derisomaltose versus placebo among consenting patients with iron-deficiency anaemia having elective major surgery on the gynaecological oncology service. Patients, clinicians and outcome assessors will be blinded. The intervention consists of a single infusion of 500–1000 mg of intravenous ferric derisomaltose administered a minimum of 21 days prior to the planned operation. The primary outcome is mean preoperative haemoglobin concentration measured 0–3 days prior to surgery in patients receiving intravenous ferric derisomaltose compared with those receiving placebo. Secondary outcomes include the following: change in haemoglobin concentration, postoperative haemoglobin concentration, perioperative blood transfusion rates, patient-reported quality of life scores (Quality of Recovery 15, Modified Short Form 36 v1, EuroQol 5-dimension 5-level and Functional Assessment of Cancer Therapy – Anaemia), surgical site infection, complication rates, length of hospital stay and readmission rate. Analyses will follow intention-to-treat principles for all randomised participants. All patients will be followed up to 60 days following surgery.

Ethics and dissemination

Ethical approval has been granted by Health Research Ethics Board of Alberta (Project ID: HREBA.CC-22–0187) and Health Canada (HC6-024-c264013). Results will be disseminated through presentation at scientific conferences, peer-reviewed publication and social and traditional media.

Trial registration number

NCT05407987.

STRENGTHS AND LIMITATIONS OF THIS STUDY.

• Adequately powered for primary biochemical outcomes.

• Adequately blinded and randomised for patient-centred outcomes..

• Single-centre study will evaluate feasibility of more generalisable multicentre clinical trials.

• Limited in power for secondary outcomes, for hypothesis generation.

Introduction

Blood is a scarce, costly and vital resource in the perioperative period. A recent analysis of gynaecological oncology surgery demonstrated a perioperative transfusion rate of 13.8%.¹ Blood transfusion following some gynaecological oncology procedures (eg, interval debulking surgery after neoadjuvant chemotherapy) can occur in as many as 50% of patients.² The incidence of anaemia (<120 g/L) in gynaecological oncology patients has been reported to be as high as 49.1% at presentation and up to 74.8% over the course of surgical or chemotherapeutic treatment.³ Iron deficiency has been reported in approximately 35% of patients with a gynaecological malignancy.⁴ Correction of anaemia is a core element of preoperative optimisation in Enhanced Recovery After Surgery (ERAS) guidelines.⁵ Blood transfusions are known to be immunosuppressive and carry immediate and long-term risks for cancer patients.⁶ Although often required for haemodynamic stability, allogeneic blood transfusions affect the immune system through the following: suppression of cytotoxic T cells and monocytes, inhibition of IL-2 production, release of immunosuppressive prostaglandins and upregulation of suppressive T regulatory cells.⁶ Preoperative blood transfusion in gynaecological oncology patients is associated with higher rates of surgical site infection, length of stay, composite morbidity, cancer recurrence, and mortality.^{1 7} Up to 23.5% of patients have a decreased hematocrit prior to gynaecological oncology surgery,¹ and up to 31.7% of patients undergoing primary debulking surgery require perioperative red blood cell transfusion.⁷ Preoperative anaemia in this population is likely multifactorial: peritoneal carcinomatosis may lead to iron deficiency due to impaired gut absorption, or decreased oral intake, tumour burden may increase losses due to bleeding, and treatments such as neoadjuvant chemotherapy may impair erythropoiesis.^{1 6} Surgical blood loss is also a factor in transfusion rates, as radical and cytoreductive surgery required for gynaecological malignancy is associated with increased transfusion rates.⁷

Preoperative intravenous iron formulations have been shown in benign gynaecology and other surgical specialities to increase preoperative haemoglobin and decrease postoperative transfusion rates.^{8 9} Previous randomised trials in abdominal surgery have demonstrated up to a 60% reduction in allogeneic blood transfusion rates for those patients receiving pre- and postoperative intravenous iron supplementation.⁹ Oral iron supplementation requires 4–6 weeks of treatment with known gastrointestinal side effects and variable compliance,¹⁰ while a cancer diagnosis often requires expedited surgery. In oncology patients undergoing surgery, oral iron absorption in the duodenum can be impaired by inflammatory mediators (eg, hepcidin) induced by the surgery or underlying malignancy.^{11 12}

Intravenous iron has been shown to decrease the need for allogeneic blood transfusion in gynaecologic oncology patients undergoing chemotherapy.^{10 13} The role of intravenous iron in the perioperative period is less well known, especially when administered in the relatively short time between diagnosis and surgery. Ferric derisomaltose (FDI) is a new formulation of iron consisting of a matrix of the carbohydrate derisomaltose and iron. The slow release of iron and low risk of free-iron toxicity afforded by this formation allow high doses of iron to be administered in one to two intravenous infusions, thereby rapidly replenishing iron stores.¹⁴

The Intravenous Iron in Colorectal Cancer-Associated Anaemia (IVICA) trial by Keeler et al found that intravenous iron did not reduce the need for blood transfusion in patients undergoing colorectal surgery for malignancy but did result in a greater improvement in their mean haemoglobin levels by the time of surgery compared with oral supplementation (15.5 g/L vs 5 g/L, p<0.001).¹⁵ Furthermore, subsequent analysis of this population demonstrated that intravenous iron improved patient quality of life both pre-and postoperatively compared with oral iron.¹⁶

The recently published Preoperative Intravenous Iron to Treat Anaemia Before Major Abdominal Surgery (PREVENTT) trial¹² did not identify a difference in postoperative blood transfusion following major open abdominal surgery between patients receiving intravenous ferric carboxymaltose and those receiving placebo. There were methodological limitations with the PREVENTT study that may have impacted its ability to assess the benefit of intravenous iron in major abdominal surgery. In the PREVENTT study, the time from iron infusion to surgery was 10–42 days, with a median time of 15 days. The demonstrated improvement in haemoglobin following carboxymaltose infusion was only 4.7 g/L at the time of surgery, and preoperative anaemia was only corrected in 21% of patients. The effect of intravenous iron in this study was more pronounced in the late postoperative period; 8 weeks following the operation, patients receiving intravenous iron had haemoglobin levels that were 10.7 g/L higher than those receiving placebo. Despite having a similar immediate postoperative haemoglobin concentration and similar rates of transfusion, patients receiving intravenous iron had a lower rate of hospital readmission than those with placebo.¹² Therefore, we will conduct the Ferric derisomaltose and Outcomes in the Recovery of Gynecologic oncology: ERAS (Enhanced Recovery After Surgery) (FORGE) study. This randomised double-blinded parallel-group placebo-controlled trial will test the hypothesis that FDI provided at least 21 days prior to surgery for gynaecological malignancy will improve preoperative haemoglobin concentration (primary objective) and improve postoperative haemoglobin concentration, blood transfusion rates and quality of life (secondary objectives) compared with placebo.

Methods and analysis

Study design and setting

We will conduct a patient-, clinician- and assessor-blinded parallel-arm randomised placebo-controlled trial of FDI compared with placebo (normal saline (NS)) in patients undergoing surgery for gynaecological malignancy at an academic tertiary care centre. This protocol is reported in keeping with the Standard Protocol Items: Recommendations for Intervention Trials guidelines.¹⁷ Research Ethics Board (REB) approval has been granted from Health Research Ethics Board of Alberta (Project ID: HREBA.CC-22–0187), and regulatory approval has been granted by Health Canada (HC6-024-c264013). Eligibility criteria are outlined in Box 1.

Box 1. Inclusion and exclusion criteria for the Ferric derisomaltose and Outcomes in the Recovery of Gynecologic oncology: ERAS (Enhanced Recovery After Surgery) (FORGE) trial.

Inclusion criteria

• Signed written informed consent prior to initiation of any study-specific activities/procedures.

• Age ≥18 years old.

• Patients undergoing elective major surgery on the gynaecological oncology service with the following criteria will be considered for inclusion:

  • The indication for the operation may be for suspected or proven gynaecological malignancy.

  • Major surgery is defined as an operation of a duration of 1 hour or greater, with an Aletti complexity score (online supplement appendix 1) of at least 1.

  • The expected time from recruitment to surgery is 28–90 days.

• Screening haemoglobin less than 120 g/L and transferrin saturation (TSAT) <20%.

• Randomisation and administration of study infusion a minimum of 21 days and maximum 90 days before planned operation.

• Negative pregnancy test for women of childbearing potential (WOCBP) (within 7 days prior to treatment).

• WOCBP must adhere to the contraception requirement from screening throughout the study period until 6 weeks post treatment.

• Laboratory data used for determination of eligibility (haemoglobin and transferrin saturation) at the baseline visit must not be older than 4 weeks.

Exclusion criteria

• Known history of acquired iron overload, or family history of haemochromatosis or thalassemia, or TSAT >50%.

• Known alternative cause for anaemia (eg, B12 or folate deficiency, or haemoglobinopathy).

• Known hypersensitivity to ferric derisomaltose/iron isomaltoside (Monoferric) or its excipients.

• Temperature >38°C or patient on non-prophylactic antibiotics.

• Known chronic liver disease or active hepatitis.

• Received erythropoietin or intravenous iron therapy within previous 12 weeks prior to planned study drug treatment.

• Alanine transaminase or aspartate transaminase above three times the upper limit of normal range.

• Immunosuppressive therapy (for solid organ transplant) or renal dialysis (current or planned within the next 12 months following treatment with study drug or placebo).

• Unfit for elective surgery.

• Pregnancy or lactation.

• Unable to fully comprehend and/or perform study procedures and patients with psychiatric illness/social situations/substance abuse that would limit compliance with study requirements.

• Cervical cancer with an International Federation of Gynaecology and Obstetrics clinical stage of 2A or greater.

• Participants are not permitted to participate in additional parallel investigational drug or device studies.

Intervention

Patients who meet eligibility criteria and have performed written informed consent will be randomised to receive intravenous iron isomaltoside or placebo at between 21 and 90 days preceding surgical intervention. Before randomisation, patients will be confirmed eligible for the trial and have a haemoglobin level measured within the preceding 4 weeks. Randomisation will be done using minimisation taking into account baseline haemoglobin (<100/≥100 g/L). Patients will be randomised to receive the active treatment (FDI/iron isomaltoside) or placebo (NS). Iron infusion will not be administered within 1 week of concurrent chemotherapy (given associated side effect profile).

The product will be prepared by an unblinded pharmacy member and administered by an unblinded staff member; the patient and second monitoring staff member will remain blinded. Patients will be closely monitored for signs of hypersensitivity during infusion and for at least 30 min following administration of the treatment.

Up to 1000 mg of Monoferric (FDI/iron isomaltoside 1000) (Pharmacosmos A/S, Denmark) or NS will be administered. Patients randomised to the intervention arm will be administered 500 mg or 1000 mg of intravenous Monoferric in 100 mL NS over 1 hour, and those in the placebo arm will be administered 100 mL of NS over 1 hour. Dosing of Monoferric will be dosed based on the product monograph in a simplified fixed-dose fashion (found below). This dosing scheme will ensure no patient exceeds the manufacturer’s recommended dose of 20 mg/kg bodyweight.

Participants with bodyweight <50 kg	Participants with bodyweight >50 kg
500 mg	1000 mg

Preoperative, in-hospital and postoperative care

As part of the study, the patient will be asked to stop taking iron pills for a period of 5 days after the study intervention, after which the patient may resume any iron pills as directed by their prescribing physician.

All other aspects of perioperative management will be at the discretion of treating clinicians. Perioperative management will be routine, according to established ERAS protocols at our institution.¹⁸

Primary outcome

The primary outcome for this trial is absolute preoperative haemoglobin concentration. This will be measured 0–3 days prior to the participant’s scheduled operation for gynaecological malignancy.

Secondary outcomes

Secondary outcomes will reflect three specific domains: (1) biochemical response to treatment, (2) clinical outcomes and (3) patient-reported quality of life. Haemoglobin response will be measured by the change in haemoglobin concentration from starting/trial entry to post-treatment/preoperative haemoglobin (between 0 and 3 days preoperatively), postoperative haemoglobin concentration at 28 and 60 days as well as persistence of iron-deficiency anaemia at 60 days post operation as measured by transferrin saturation. Clinical outcomes will include incidence of blood transfusions postoperatively, number of blood transfusions required, rate of surgical site infection, rate of hospital readmission, length of hospital stay and rates of overall complications following the operation up to 30 days. Patient-reported quality of life will be assessed preoperatively, in hospital (24 hours after operation), and 28 and 60 days following the operation and will be measured by generalised validated scoring tools (EuroQol 5-dimension 5-level (EQ-5D-5L),¹⁹ Modified Short Form 36 v1 (SF-36) (RAND Corporation, Santa Monica, California)²⁰) as well as those tailored to surgical (Quality of Recovery 15 (QoR-15))²¹ and anaemia-related quality of life (Functional Assessment of Cancer Therapy – Anaemia (FACT-An)).²² The QoR-15 is a validated short form version of the QoR-40 scoring system that captures measures of postoperative recovery over the domains of pain, physical comfort, independence, psychological support and emotional state. The EQ-5D-5L is a metric developed by the EuroQol Group that assesses five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The baseline EQ-5D-5L will be completed 0–28 days prior to the intervention, 0–3 days preop, 28 days post operation (± 5 days) and 60 days post operation (± 7 days). The SF-36 is a 36-item health survey that has been validated to assess eight health concepts: physical functioning, bodily pain, emotional well-being, social functioning, energy/fatigue, general health perceptions and role limitations due to physical health or personal/emotional problems. The FACT-An is a 47-item survey to assess symptoms of anaemia in cancer patients in the domain of physical well-being, social/family well-being and emotional and functional well-being.

Sample size

The sample size requirement was calculated for the primary objective of preoperative haemoglobin as a continuous variable. To detect an absolute difference in preoperative haemoglobin levels of 10 g/L (1 g/dL) with 99% power, a SD of 10 g/L and a type I error rate of 5%, it will require 37 patients per arm.

The PREVENTT trial noted a 4% drop-out and cancellation of surgery rate.¹² Accounting for an additional 6% of patients who undergo surgery in a more urgent fashion (less than 21 days), we obtain a target recruitment of 41 patients per arm.

Recruitment

All consecutive gynaecological oncology patients presenting for surgical intervention for suspected or confirmed gynaecological cancer (endometrial, ovarian or cervical cancer) will be screened for anaemia and identified from outpatient clinics, inpatient visits, multidisciplinary meetings and outpatient therapy visits (chemotherapy). The study is planned to start recruitment in February of 2024 and complete enrollment in September of 2025. Screening bloodwork will be implemented prior to the first visit with the gynaecological oncology team or immediately on first appointment. All patients with haemoglobin levels lower than 120 g/L and transferrin saturation of <20% will be approached for inclusion into the study. Whenever possible, patients will be screened for anaemia at first presentation to the gynaecological oncology team (ie, initial consultation). Participants will formally be screened for inclusion following signing of consent. All recruitment for FORGE II will be performed at Tom Baker Cancer Centre, Calgary, Alberta, Canada.

Assignment of the intervention

Before randomisation, patients will be confirmed eligible for the trial and have a haemoglobin level measured within the preceding 4 weeks. Randomisation will be done using minimisation taking into account baseline haemoglobin (<100/≥100 g/L). Patients will be randomised to receive the active treatment (FDI/iron isomaltoside) or placebo (NS). Study personnel will access the randomisation sequence via a central secure internet-based application to ensure allocation concealment.

Blinding

The FDI/iron isomaltoside is dark brown in appearance; blinding will be obtained by shielding the patients and caregivers, study team, sponsor and outcome assessors from seeing the preparation of the drug by covering both the drug administration bag and intravenous lines with opaque ultraviolet light shielding and/or black tubing. The investigational product (FDI) and placebo will be masked using the same shielding equipment. The drug will be prepared by an unblinded pharmacy staff member who will not be present during the administration of the drug. The drug will be administered by an unblinded nurse. All patients will be monitored during the trial drug administration as per normal clinical practice by a blinded nurse; any adverse events will be documented. If necessary, disposal of the administration kit will be done by the unblinded staff member.

Unblinding

The blinding to the patients or other medical staff may be broken for valid medical or safety reasons where it is necessary for the treating healthcare professional to know which treatment the patient has received (eg, in the case of a serious adverse event where it is necessary for the health caregiver to know which treatment the patient is receiving before the participant can be treated). Unless clinically necessary, where possible, all other members of the research team should remain blinded.

Acceptable concomitant medications

Oral iron therapy is acceptable but must be recorded and should not be given the day of treatment with iron isomaltoside and should not be started for at least 5 days following injection of iron isomaltoside. Iron chelating medications may be used for treatment of iron overdose.

Prohibited concomitant medications

Immunosuppressive therapy for organ transplant and renal dialysis are not allowed prior to or during the study. Erythropoietin and intravenous iron (outside of the trial treatment) are not allowed during the study. Any participant receiving erythropoietin or intravenous iron treatment during the trial or within 12 weeks prior to starting the trial will be excluded from the trial.

Data collection and management

An electronic data capture system will be used in this trial. This data will be entered by the site into the electronic data capture system. Data collection will be completed by research personnel or the site investigator either in person or over the telephone. Data on patient demographic, biochemical, and surgical characteristics as well as data on complications, length of stay and transfusion rates will be captured in the ERAS Interactive Audit System (EIAS) by an outcome assessor that will be blinded to the patients’ study arm. The EIAS is a secure electronic database used internationally to collect and audit outcomes of patients undergoing surgery under an ERAS protocol. The patient medical charts, anaesthetic records, electronic health records and validated questionnaires (FACT-An, EQ-5D-5L, QoR-15, SF-36) will serve as source documentation which will subsequently be entered into the EIAS or trial database.

Data on number of preoperative blood transfusions will be obtained to ensure balance between the groups. Data on complications will be ascertained by follow-up interview and confirmed with review of medical records. The investigator will retain all study records and source documents for 15 years after the close of the study as per Health Canada record retention requirements. If the maximum period required by institution procedures or local regulations is longer, the investigator shall comply with the longer period of record retention.

Patient and public involvement

Our trial protocol was reviewed by an institutional research ethics board including members of patient groups and public advocates.

Data analysis

Descriptive statistics (mean and SD for continuous variables or median and interquartile range for skewed distributions, and frequency and proportion for categorical variables) will be used to report characteristics of participants in each arm at baseline as well as compliance with ERAS protocols. Preoperative haemoglobin levels (primary outcome) will be compared as a continuous variable with Student’s t-test on an intention-to-treat principle. Preoperative haemoglobin concentration will be adjusted for concomitant use of oral iron, time from treatment to surgery and the use of neoadjuvant chemotherapy with linear regression analysis.

Planned subgroup analysis of preoperative haemoglobin concentration will be undertaken based on neoadjuvant chemotherapy prior to surgery compared with primary surgery. Relative risk of perioperative transfusion, surgical site infection, readmission within 30 days and mortality within 30 days will be compared using Fisher exact test. Median postoperative length of stay will be compared between groups using Wilcoxon rank-sum test, and odds of discharge following surgery will be represented as HR for discharge and will be compared by Kaplan-Meier survival analysis. Cost-effectiveness will be compared using pre-existing data on the cost of iron supplementation, cost of blood transfusion and associated interventions and cost of hospitalisation and readmission.²³ Data will be analysed on an intention-to-treat basis, with sensitivity analysis by per protocol performed for hypothesis generation.

Ethics and dissemination

Freely given written informed consent will be obtained by a physician (or other suitably qualified personnel) prior to enrolment. The person taking consent will be trained in International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use Guideline for Good Clinical Practice (ICH GCP) and be delegated this responsibility by the qualified investigator. Investigators must ensure that patients are fully informed about the purpose, potential risks and other critical issues regarding clinical trials in which they volunteer to participate.

The sponsor will provide an appropriate informed consent form which will include all elements required by ICH GCP and applicable regulatory requirements.

Dissemination plans will include local, national and international presentations at scientific conferences, as well as submission to peer-reviewed scientific journals. Press releases will engage lay media, and social media will be further leveraged to disseminate results. Development of brief overviews and visual abstracts will occur and will be shared with study partners, patients and knowledge users.

Confidentiality

The investigators will assure that participants’ anonymity will be maintained and that their identities are protected from unauthorised parties. On case report forms, patients will not be identified by their names, but by an identification code. Investigators will keep patients’ written consent forms and a patient enrollment log at the site showing codes, names and addresses.

Data retention

The investigator will retain and have unrestricted access to all study records for 15 years after the close of the study as per Health Canada record retention requirements.

Protocol amendments

All Health Canada-approved protocol amendments must receive local REB approval prior to implementation and will be disseminated to relevant parties through the trial team.

Monitoring

The Data Safety Monitoring Committee (DSMC) will be specific to this study and will be composed of independent reviewers with relevant medical and scientific knowledge and expertise. The members of the board will be identified by the sponsor and will be completely independent of the trial being monitored. The purpose of the DSMC is to advise on safety data, lack of efficacy and any other considerations within the charge of the board.

Appropriate data summaries will be provided to the DSMC at the time of the analysis regarding both safety and efficacy. The DSMC will meet every 6 months during the trial and following the completion of data collection from the last enrolled patient and creation of secure dataset until the time at which the final statistical analysis is completed and following publication of the data.

The DSMC may also be convened at any time to evaluate patient safety and trial efficacy concerns on discretion of the sponsor or DSMC. The DSMC will communicate to the sponsor if the trial is to continue, be modified or stopped as a result of the DSMC review.

Discussion

Gynaecological cancer patients have an increased risk of perioperative anaemia and subsequent blood transfusion.^{1–4 7} Preoperative correction of anaemia is a key element of ERAS protocols; however, blood transfusions are a rare and costly resource which carry significant short-term, long-term and oncological risks.^{2 5 7} This pilot double-blinded randomised controlled trial will build on the work of the PREVENTT and IVICA trials and will provide evidence of the effect of preoperative intravenous FDI on preoperative haemoglobin concentration in gynaecological oncology patients and exploratory results on outcomes of patient well-being, as well as complications, length of stay and costs. Moreover, this pilot study will determine the feasibility and assist in the design of planned larger trials in this population that will focus on patient-reported outcomes, as well as rarer, but clinically impactful outcomes such as infections, return to intended treatment and oncological outcomes. The blinded nature of this trial will allow assessment of patient-reported outcomes while decreasing potential bias from the placebo effect.

Strengths and limitations

This study will provide data on efficacy and feasibility of a novel treatment with the potential to impact outcomes of gynaecological cancer surgery. Through adequate blinding, it will provide robust and low-bias assessment of patient-reported outcomes via validated tools for individuals undergoing surgery, as well as those with anaemia. There are potential limitations with this trial, many of which we aim to mitigate in our protocol. Patients who require neoadjuvant treatment, such as chemotherapy prior to interval debulking surgery, may see a different response to iron therapy given the myelosuppressive effects of chemotherapy despite studies demonstrating efficacy of this treatment in this population.^{10 13} The time from treatment to surgery will be longer for patients undergoing preoperative chemotherapy compared with those undergoing surgery immediately. We will address this with statistical correction and subgroup analysis. Similarly, patients who require adjuvant treatment (either radiotherapy or chemotherapy) rapidly after surgery may have altered haemoglobin levels at 60 days after surgery. Randomisation should balance this effect, but planned regression will yield information about the clinical effect of this on outcomes. As a pilot study, the results of this study will be less generalisable and less powered than a large multicentre study, especially for secondary outcomes. By assessing all common disease sites in gynaecological oncology, this study provides generalisable results to the population but introduces heterogeneity in the results. The subgroup analysis by disease site will inform the design of and inclusion criteria of future studies to focus on those patients at greatest risk of iron-deficiency anaemia and to look at potential differences in response based on disease site.

Conclusion

The FORGE trial will evaluate the efficacy of intravenous FDI in improving preoperative haemoglobin concentration in patients with iron-deficiency anaemia undergoing gynaecological oncology surgery. The proposed study will produce pilot data that will inform the feasibility and design of larger, outcome-based trials.

Ethics statements

Patient consent for publication

Not applicable.