Clinical trial NCT05681871: South African Paediatric Surgical Outcomes Study 2
Official title: A South African Multi-centre Pilot Trial to Assess the Feasibility and Clinical Efficacy of Preoperative Oral Iron to Treat Preoperative Iron-deficiency Anaemia in Children Undergoing Elective Noncardiac Surgery
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Paediatric Surgery
Anaemia
Iron Deficiency Anemia
Iron
Prospective Studies
Interventional Studies
Lead sponsor: University of Cape Town
Sponsor class: OTHER
Collaborators: name: University of Stellenbosch
name: University of KwaZulu
First posted: 2023-01-12
Enrollment: 762
Sex: ALL
Minimum age (years): 6
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Prospective interventional quasi-experimental pre-post study South African multi-centre
Primary purpose: TREATMENT

Brief summary: Preoperative anaemia has been shown to be associated with worse outcomes after surgery in both adults and children. Limited research has been done on how common preoperative iron-deficiency anaemia (IDA) is in children and how best to treat it. Oral iron is a relatively cost-effective treatment for IDA. This study aims to show whether giving children with IDA oral iron for 6-12 weeks before their surgery significantly improves their haemoglobin.

Detailed description: Studies in both paediatric and adult patients have shown an association between preoperative anaemia and increased postoperative morbidity and mortality, and transfusion rates. The incidence of preoperative anaemia in the secondary analysis of the SAPSOS cohort of children who underwent noncardiac surgery was 46.2%. IDA has been shown to represent up to 30% of preoperative anaemia in adults. Iron deficiency and IDA are of even greater concern in children, because of the negative impact it may have on cognitive performance.

A recent Cochrane review on the role of preoperative iron in reducing perioperative blood transfusion in adult patients found no significant reduction in the administration of allogeneic blood transfusion in patients who had received preoperative iron compared with those who did not. These findings were supported by the Preoperative intravenous iron to treat anaemia before major abdominal surgery (PREVENTT) trial which found no difference in blood transfusion or death between the patients who did and did not receive intravenous iron. However, these findings have generated much discussion in the literature and concerns have been raised about the clinical application of this study. The mean haemoglobin (Hb) difference between the two groups post intervention (0.47g.dl-1) highlights the need for greater understanding of the impact of an intervention on the absolute or relative increase in Hb when designing trials looking at the impact of iron treatment on perioperative outcomes. Dosing regimens of preoperative oral iron varies widely between studies further complicating the ability to draw conclusions of the role of oral iron in the treatment of preoperative anaemia.

In contrast with the findings of the Cochrane review and the PREVENTT trial, a meta-analysis of patient blood management programme (PBM) studies, many of which include preoperative iron treatment as a component, found that there was a reduction in exposure to red cell transfusions. Although, the meta-analysis also found the implementation of PBM was not associated with a reduction on in-hospital mortality or 30-day mortality, there was no additive benefit from multiple interventions and no trial showed that PBM were cost-effective. Not included in this meta-analysis were recently published studies on the implementation of preoperative anaemia screening clinics in adults in elective colorectal surgery and major surgery which demonstrated reductions in red cell transfusions, length of stay, and net costs in patients with IDA who were treated with preoperative intravenous iron. Similarly, a large study from Western Australia reported significant reductions in cost associated with the use of blood products, and improved patient outcomes, after implementation of a PBM.

Studies investigating the impact of increasing preoperative Hb on perioperative outcomes in children are primarily focused on blood loss and blood transfusion rates in surgery in which significant bleeding and frequent blood transfusion are anticipated and most of the children in these studies received preoperative erythopoeitin. The impact of preoperative oral iron as a stand-alone intervention to increases preoperative Hb are limited to 2 studies. A single retrospective study has reported on the impact of the introduction of preoperative oral iron without erythropoeitin (EPO) in children undergoing spinal surgery. They found a significant difference in intraoperative transfusion rates in patients who received a longer duration of preoperative oral iron therapy. The major limitation of the study was a lack of preintervention Hb, precluding the ability to assess the effect of iron supplementation on delta Hb. A subsequent study reviewing the impact of preoperative oral iron in paediatric cardiac patients found that iron supplementation resulted in an increase in preoperative Hb levels which was associated with reduced red blood cell transfusion volumes.

Given the high incidence of preoperative anaemia in children having surgery in South Africa in the public sector and its association with poorer postoperative outcomes, it is important to assess the feasibility of a pragmatic intervention to treat preoperative anaemia in the context of a resource-constrained setting. Although intravenous iron in combination with EPO may be more effective and have fewer side effects, oral iron is relatively inexpensive and widely available in South Africa. Regular deworming may also play an important role in the treatment of preoperative anaemia and has been shown to be an effective intervention to increase baseline Hb in school age children from low- and middle- income countries. We hypothesise that the implementation of preoperative anaemia screening and treatment of anaemic patients with a minimum of 6 weeks supplementation with oral iron will have a clinically significant effect on increasing the Hb in patients with preoperative IDA.

STUDY OBJECTIVE To evaluate the efficacy of oral iron supplementation in children diagnosed with preoperative IDA undergoing noncardiac surgery.

STUDY DESIGN Pre and post- South African multi-centre interventional study of oral iron supplementation to treat IDA in paediatric patients (age \>6 months and \<16 years) admitted to participating hospitals undergoing elective non-cardiac surgery. The intention is to present a representative sample of paediatric surgical patients with preoperative anaemia. This study will run from January 2023 until July 2023.

ETHICS APPROVAL Ethics approval will be in place at each hospital site prior to recruitment of patients. Informed consent, and assent where appropriate, must be obtained for each participant enrolled in the study.

IMPORTANCE OF STUDY Preoperative anaemia is associated with significant morbidity and mortality. The information gained from this study will contribute to a greater understanding of the incidence of preoperative IDA in children in South Africa and give insight into the feasibility and efficacy of oral iron supplementation to treat preoperative IDA.

Eligibility criteria: Inclusion Criteria:

* Age \> 6 months to \<16 years
* Noncardiac surgery
* Elective surgery
* Anaemic as per World Health Organisation criteria

Exclusion Criteria:

* Patient or parent refusal
* Unable to obtain written consent at the surgical outpatient clinic
* Surgery planned within 4 weeks from surgical outpatient visit
* Known history of acquired iron overload, family history of haemochromatosis or thalassemia
* Known reason for anaemia (e.g., untreated vitamin B12 or folate deficiency or haemoglobinopathy)
* Treatment with oral iron, erythropoietin, IV iron therapy or blood transfusion in the previous 12 weeks
* Known hypersensitivity to oral iron or other contraindication to oral iron
* Temperature \> 38.0 °C or receiving non-prophylactic antibiotics
* Acute liver failure

Primary outcomes:
measure: Delta Haemoglobin = Change in average haemoglobin pre- and post- oral iron supplementation
timeFrame: 6-12 weeks
Secondary outcomes:
measure: Incidence of iron-deficiency anaemia
timeFrame: 18 months
Other outcomes:
Locations:
city: Cape Town
country: South Africa
facility: Tygerberg Hospital
state: Western Cape
city: Cape Town
country: South Africa
facility: Red Cross War Memorial Children's Hospital
state: Western Cape
Study officials:
affiliation: University of CapeTown
name: Heidi M Meyer, MBChB
role: PRINCIPAL_INVESTIGATOR
References: