Clinical trial NCT05744219: Improved Recovery by Iron Following Surgery With Blood Loss, the IRIS-trial
Official title: Improved Recovery by Iron Following Surgery With Blood Loss, a Double-blind Multi-centre Randomized Controlled Phase III Drug Trial (the IRIS-trial)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Surgery
Liver Metastases
Liver Cancer
Pancreas Cancer
Aortic Aneurysm
Lead sponsor: Uppsala University Hospital
Sponsor class: OTHER
First posted: 2023-02-24
Enrollment: 338
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: At end of surgery, peri-operative blood loss is determined and if 400-4000 ml, the patient is randomised to iv Ferric Carboxymaltose 1000 mg or placebo.
Primary purpose: TREATMENT

Brief summary: The aim of the study is to investigate if iv iron formulation improve recovery after surgery with blood loss.

Post-operative anaemia is a common debilitating condition after major surgery due to a combination of preoperative iron deficiency anaemia (IDA) and per-operative blood loss. Median blood loss following hepatopancreatobiliary (HPB) and complex aortic surgery typically range between 500-1000 ml. Bioavailability of iron may be a rate limiting factor in erythropoiesis in anaemia secondary to blood loss. For the IRIS trial, it is hypothesized that intravenously (iv) administered Ferric Carboxymaltose after a per-operative blood loss of 400-4000 ml, improves post-operative recovery and reduces the RBC transfusion.

Patients scheduled for elective HPB surgery or complex aortic surgery will be screened for eligibility and recruited into the study.

By the end of the surgical procedure, if blood loss is estimated to 400-4000 ml, the patient is randomized 1:1 to iv 1000 mg Ferric Carboxymaltose or placebo.

The primary endpoint is a composite of death, number of RBC transfusions, post-operative severe anemia (Hb \<80 g/L) and FACT-An Quality of life (QoL) five weeks after surgery, assessed by win ratio.

The trial will also examine effects on; a) levels of Hb; b) markers of erythropoiesis and iron bioavailability; c) post-operative complications; d) post-operative recovery; e) performance status; f) subgroups based on type of surgery and degree of anemia and iron deficiency; g) re-admissions; h) long term outcome based on patient medical records and i) how post-operative recovery differs between those with low (\<400 ml), high (400-4000 ml) and very high (\>4000 ml) per-operative blood loss.

Recruitment will continue until 338 patients are randomized or 304 have completed the five week follow up

The coordinating center of the trial is the Department of Surgery at Uppsala University Hospital. Participating sites are also Linköping University Hospital and Lund University Hospital, all in Sweden. Other sites may be added.


Eligibility criteria: Inclusion Criteria:

1. Provision of written informed consent
2. Male and female patients
3. Weight \> 50 kg
4. \> 18 years of age
5. Scheduled for complex aortic surgery, liver resection or pancreatic resection

Exclusion Criteria:

1. Short expected survival (less than six months)
2. Intra-venous iron therapy within one month prior to surgery
3. Severe anaemia (B-Hb \<80 mg/L) prior to surgery
4. Contraindication to Ferric Carboxymaltose according to SmPC
5. Iron overloading disorder, i.e. hemochromatosis
6. Risk of small for size future liver remnant
7. Pre-operative renal replacement therapy
8. Enrolled in another drug or medical device study within 30 days prior to enrolment of the current study
9. Another planned major surgical procedure before the five week follow up
10. Unsuitable for inclusion according to the investigator
11. Pregnancy

Primary outcomes:
measure: Recovery after iv Iron
timeFrame: Five weeks
Secondary outcomes:
measure: Hb
timeFrame: One to five weeks
measure: Complications
timeFrame: One to five weeks
measure: Recovery
timeFrame: One to five weeks
measure: Performance status
timeFrame: Five weeks
Other outcomes:
Locations:
city: Uppsala
country: Sweden
facility: Uppsala University Hospital
state: Sverige
Study officials:
References: