Perioperative Iron for Colorectal Cancer (PICoC Study) (PICoC)

An Open Label Randomised Trial to Assess the Efficacy of Post-Operative Ferric Maltol Vs Standard Care for Anaemia Following Colorectal Cancer Surgery

The PICoC study aims to investigate whether oral ferric maltol given postoperatively offers an improvement in patient and clinician reported outcomes compared to standard care.

Study Overview

• Status: Recruiting
• Conditions: Cancer Colon
• Intervention / Treatment: Drug: oral ferric maltol

Detailed Description

Colorectal cancer is associated with iron deficiency anaemia in 40-60% of cases. This anaemia can lead to poorer post-operative outcomes such as higher complication rates, increased length of stay and reduced survival. There has been a recent shift towards the correction of preoperative anaemia in order to optimize perioperative outcomes. However, despite improvements in preoperative haemoglobin there exists a group of patients who develop worsening or recurrent anaemia in the post-operative period. Without intervention up to 90% of patients in the immediate postoperative period may develop anaemia. This is not unexpected given the peri-operative blood loss; poor nutritional intake in the postoperative period; and the frequent blood sampling for laboratory tests. Our data from previous trials has demonstrated that despite preoperative intravenous iron therapy 75% of patients remain anaemic at the time of their colorectal cancer operation. In addition, our unpublished data has found that around 1/3 of patients treated with preoperative iron therapy develop a recurrence of their anaemia in the first year postoperatively. Studies have identified that traditional oral ferrous iron supplementation is largely ineffective for the treatment of postoperative anaemia. However, a newer oral iron preparation - ferric maltol (Ferracru) has been found to be better tolerated and more efficacious than ferrous iron. This study aims to evaluate whether the use of iron supplementation in the form of Feraccru could lead to a more sustained or improved a response in haemoglobin if given after a colorectal cancer operation. Improving this postoperative anaemia may have important implications for clinician and patient reported outcomes. The Perioperative Iron in Colorectal Cancer (PICoC) trial will run as a feasibility study to assess the proposed design, recruitability and outcome measures. Anaemic colorectal cancer patients treated with preoperative intravenous iron will be randomised in an open label design to receive a course of Ferric maltol (intervention group) or standard care (control group) postoperatively. Secondary outcome measures will focus on a comparison of change in blood indices, quality of life, allogenic red blood transfusion rates and postoperative complications between groups. Follow up will continue until the first postoperative outpatient visit at approximately 12 weeks following discharge.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Matthew Brookes; Phone Number: 01902307999; Email: matthew.brookes@nhs.net
• Study Contact Backup: Name: Lorraine Jacques; Email: lorraine.jacques@nhs.net

Study Locations

• United Kingdom
  • Wolverhampton, United Kingdom
    • Recruiting
    • The Royal Wolverhampton NHS Trust
    • Contact: Matthew Brookes; Phone Number: 01902307999; Email: matthew.brookes@nhs.net
    • Principal Investigator: Matthew Brookes
    • Sub-Investigator: Nuha Yassin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participant is willing and able to give informed consent for participation in the study.
• Male or Female, aged 18+ years.
• Diagnosed with histologically or radiologically diagnosed colorectal adenocarcinoma.
• Anaemic at point of diagnosis of colorectal adenocarcinoma (Defined as haemoglobin 10g/L below WHO criteria: 120g/L for males and 110g/L for females, to account for a 10% fluctuation in Hb)
• Undergoing surgery for colorectal cancer with curative intent.
• Date of planned surgery is ≥ 14 days from date of planned initiation of recruitment.
• Able (in the investigators opinion) and willing to comply with all study requirements.
• Willing to allow his or her General Practitioner and consultant, if appropriate, to be notified of participation in the study.

Exclusion Criteria:

• Patients who do not have a histological diagnosis of colorectal adenocarcinoma
• Female participants who are pregnant, lactating or planning a pregnancy during the course of the study.
• Patients with evidence of iron overload or disturbances in utilisation of iron as stated in the product SPC.
• Previous gastric, small bowel or colorectal surgery (where ≥50% of stomach or terminal ileum has been resected)
• Chemotherapeutic treatment within the last 4 weeks.
• Known previous anaemia not attributable to colorectal carcinoma (i.e. anaemia in patients with well established, inflammatory disorders)
• Known haematological disease.
• Features necessitating urgent surgery (e.g. obstructive symptoms).
• Previous allergy to intravenous or oral iron or related iron products.
• Patients who are unable to consent.
• Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the study, or may influence the result of the study, or the participant's ability to participate in the study.
• Participants who have participated in another research study involving an investigational product in the past 12 weeks
• Confirmed liver or lung metastases

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Standard Care
Experimental: Ferric maltol	Drug: oral ferric maltol; The intervention group will commence a course of oral ferric maltol provided oral intake has recommenced and the control group will receive standard care. All patients will have blood tests checked again at day 3 and day 5 postoperatively if they remain as an inpatient. If they are found to be anaemic on either of these two blood tests they will, at this stage, enter their allocated treatment pathway. If a patient shows no evidence of anaemia on either day 2, 3 or 5 blood tests they will be withdrawn from the study. Patients will continue treatment according to their randomisation allocation until 12 weeks after the operation, at which point the patient attends a routine surgical outpatient follow-up clinic. During the outpatient visit the participants will undergo their final blood testing and questionnaire completion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the feasibility of running the study, to see if it could be run as a large multi-centre study	Feasibility measures will include the number of patients: Eligible from screening; excluded and why; will stay in the study	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
whether the use of ferric maltol could improve the postoperative quality of life of patients after colorectal cancer surgery compared to standard care.	Quality of life as determined by the Functional Assessment of Cancer Therapy (FACT)-An questionnaire scoring between 0 and 184 values. Higher scores mean a better or worse outcome on different parts of the questionnaire.	1 year
whether the use of ferric maltol could improve the postoperative quality of life of patients after colorectal cancer surgery compared to standard care.	Quality of life as determined by the Short Form Health Survey questionnaire (SF-36) Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.	1 year
whether the use of ferric maltol could improve the postoperative quality of life of patients after colorectal cancer surgery compared to standard care.	Quality of life as determined by the EQ-5D-5L questionnaire which has 2 scales - the EQ-5D descriptive system (page 2 of the questionnaire) and the EQ-5D visual analogue scale (EQ VAS). Responses are coded as a number (1, 2, 3, 4 or 5) that corresponds to the respective level of severity: 1 indicates no problems, and 5 extreme problems. In this way, a person's health state profile can be defined by a 5-digit number, ranging from 11111 (having no problems in any of the dimensions) to 55555 (having extreme problems in all the dimensions).	1 year
the change in postoperative haemoglobin in response to ferric maltol compared to standard care.	change in postoperative haemoglobin in g/l	1 year
the change in postoperative ferritin levels in response to ferric maltol compared to standard care.	change in postoperative ferritin levels in ng/mL	1 year
postoperative allogenic red blood cell transfusion rates	postoperative allogenic red blood cell transfusion rates in patients receiving ferric maltol or standard care	1 year

Collaborators and Investigators

• Sponsor: The Royal Wolverhampton Hospitals NHS Trust
• Collaborators: Norgine
• Investigators: Principal Investigator: Nuha Yassin, The Royal Wolverhampton NHS Trust

Study record dates

Study Major Dates

• Study Start (Actual): May 30, 2022
• Primary Completion (Estimated): May 29, 2025
• Study Completion (Estimated): May 29, 2025

Study Registration Dates

• First Submitted: November 8, 2021
• First Submitted That Met QC Criteria: December 14, 2021
• First Posted (Actual): January 4, 2022

Study Record Updates

• Last Update Posted (Actual): December 28, 2023
• Last Update Submitted That Met QC Criteria: December 27, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Hematinics; Ferric maltol
• Other Study ID Numbers: 2021GAS120

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No