-
1.
Erythromycin prior to endoscopy for acute upper gastrointestinal haemorrhage
Adão, D., Gois, A. F., Pacheco, R. L., Pimentel, C. F., Riera, R.
The Cochrane Database of Systematic Reviews. 2023;2(2):Cd013176
Abstract
BACKGROUND Upper endoscopy is the definitive treatment for upper gastrointestinal haemorrhage (UGIH). However, up to 13% of people who undergo upper endoscopy will have incomplete visualisation of the gastric mucosa at presentation. Erythromycin acts as a motilin receptor agonist in the upper gastrointestinal (GI) tract and increases gastric emptying, which may lead to better quality of visualisation and improved treatment effectiveness. However, there is uncertainty about the benefits and harms of erythromycin in UGIH. OBJECTIVES To evaluate the benefits and harms of erythromycin before endoscopy in adults with acute upper gastrointestinal haemorrhage, compared with any other treatment or no treatment/placebo. SEARCH METHODS We used standard, extensive Cochrane search methods. The latest search date was 15 October 2021. SELECTION CRITERIA We included randomised controlled trials (RCTs) that investigated erythromycin before endoscopy compared to any other treatment or no treatment/placebo before endoscopy in adults with acute UGIH. DATA COLLECTION AND ANALYSIS We used standard Cochrane methods. Our primary outcomes were 1. UGIH-related mortality and 2. serious adverse events. Our secondary outcomes were 1. all-cause mortality, 2. visualisation of gastric mucosa, 3. non-serious adverse events, 4. rebleeding, 5. blood transfusion, and 5. rescue invasive intervention. We used GRADE criteria to assess the certainty of the evidence for each outcome. MAIN RESULTS We included 11 RCTs with 878 participants. The mean age ranged from 53.13 years to 64.5 years, and most participants were men (72.3%). One RCT included only non-variceal haemorrhage, one included only variceal haemorrhage, and eight included both aetiologies. We defined short-term outcomes as those occurring within one week of initial endoscopy. Erythromycin versus placebo Three RCTs (255 participants) compared erythromycin with placebo. There were no UGIH-related deaths. The evidence is very uncertain about the short-term effects of erythromycin compared with placebo on serious adverse events (risk difference (RD) -0.01, 95% confidence interval (CI) -0.04 to 0.02; 3 studies, 255 participants; very low certainty), all-cause mortality (RD 0.00, 95% CI -0.03 to 0.03; 3 studies, 255 participants; very low certainty), non-serious adverse events (RD 0.01, 95% CI -0.03 to 0.05; 3 studies, 255 participants; very low certainty), and rebleeding (risk ratio (RR) 0.63, 95% CI 0.13 to 2.90; 2 studies, 195 participants; very low certainty). Erythromycin may improve gastric mucosa visualisation (mean difference (MD) 3.63 points on 16-point ordinal scale, 95% CI 2.20 to 5.05; higher MD means better visualisation; 2 studies, 195 participants; low certainty). Erythromycin may also result in a slight reduction in blood transfusion (MD -0.44 standard units of blood, 95% CI -0.86 to -0.01; 3 studies, 255 participants; low certainty). Erythromycin plus nasogastric tube lavage versus no intervention/placebo plus nasogastric tube lavage Six RCTs (408 participants) compared erythromycin plus nasogastric tube lavage with no intervention/placebo plus nasogastric tube lavage. There were no UGIH-related deaths and no serious adverse events. The evidence is very uncertain about the short-term effects of erythromycin plus nasogastric tube lavage compared with no intervention/placebo plus nasogastric tube lavage on all-cause mortality (RD -0.02, 95% CI -0.08 to 0.03; 3 studies, 238 participants; very low certainty), visualisation of the gastric mucosa (standardised mean difference (SMD) 0.48 points on 10-point ordinal scale, 95% CI 0.10 to 0.85; higher SMD means better visualisation; 3 studies, 170 participants; very low certainty), non-serious adverse events (RD 0.00, 95% CI -0.05 to 0.05; 6 studies, 408 participants; very low certainty), rebleeding (RR 1.13, 95% CI 0.63 to 2.02; 1 study, 169 participants; very low certainty), and blood transfusion (MD -1.85 standard units of blood, 95% CI -4.34 to 0.64; 3 studies, 180 participants; very low certainty). Erythromycin versus nasogastric tube lavage Four RCTs (287 participants) compared erythromycin with nasogastric tube lavage. There were no UGIH-related deaths and no serious adverse events. The evidence is very uncertain about the short-term effects of erythromycin compared with nasogastric tube lavage on all-cause mortality (RD 0.02, 95% CI -0.05 to 0.08; 3 studies, 213 participants; very low certainty), visualisation of the gastric mucosa (RR 1.19, 95% CI 0.79 to 1.79; 2 studies, 198 participants; very low certainty), non-serious adverse events (RD -0.10, 95% CI -0.34 to 0.13; 3 studies, 213 participants; very low certainty), rebleeding (RR 0.77, 95% CI 0.40 to 1.49; 1 study, 169 participants; very low certainty), and blood transfusion (median 2 standard units of blood, interquartile range 0 to 4 in both groups; 1 study, 169 participants; very low certainty). Erythromycin plus nasogastric tube lavage versus metoclopramide plus nasogastric tube lavage One RCT (30 participants) compared erythromycin plus nasogastric tube lavage with metoclopramide plus nasogastric tube lavage. The evidence is very uncertain about the effects of erythromycin plus nasogastric tube lavage on all the reported outcomes (serious adverse events, visualisation of gastric mucosa, non-serious adverse events, and blood transfusion). AUTHORS' CONCLUSIONS We are unsure if erythromycin before endoscopy in people with UGIH has any clinical benefits or harms. However, erythromycin compared with placebo may improve gastric mucosa visualisation and result in a slight reduction in blood transfusion.
-
2.
Treatment Options for Gastrointestinal Bleeding Blue Rubber Bleb Nevus Syndrome: a systematic review
Rimondi A, Sorge A, Murino A, Nandi N, Scaramella L, Vecchi M, Tontini GE, Elli L
Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society. 2023
-
-
Free full text
-
Abstract
INTRODUCTION Blue Rubber Bleb Nevus Syndrome (BRBNS) is a rare challenging cause of gastrointestinal bleeding. We performed a systematic review of case reports and case series on BRBNS to gather information on the treatment options currently available. METHOD All studies reporting a case of BRBNS in humans were evaluated. Papers were ruled out whether CARE criteria and explanations on patient's selection, ascertainment, causality, and reporting were not respected or identified. PROSPERO 2021 CRD 42021286982. RESULTS BRNBS was treated in 106 cases from 76 reports. 57.5% of the population was under 18 years old, and up to 50% of the cases reported a previous treatment. Clinical success was achieved in 98 patients (92.4%). Three main types of interventions were identified: systemic drug therapy, endoscopy and surgery. After BRBNS recurrence or previous therapy failure, systemic drug therapy emerged as a preferred second-line treatment over endoscopy (p=0.01), but with a higher rate of reported adverse events when compared with surgery and endoscopy (p < 0.001). Endoscopic treatment was associated with a higher number of required sessions to achieve complete eradication when compared with surgery (p < 0.001). No differences between the three main areas were found in the overall follow-up time (p=0.19) and in the recurrence rate (p=0.45). CONCLUSION Endoscopy, surgery and systemic drug therapy are feasible treatment options for BRBNS. Systemic drug therapy was the favourite second-line treatment after endoscopic failure or recurrence of BRBNS, but adverse events were more frequently reported.
-
3.
Role of Oral Iron Supplementation for Anemia Secondary to Acute Nonvariceal Upper Gastrointestinal Bleeding: A Randomized Controlled Trial
Chang A, Rugivarodum M, Pungpipattrakul N, Akarapatima K, Suwanno K, Rattanasupar A, Ovartlarnporn B, Prachayakul V
Journal of gastroenterology and hepatology. 2023
-
-
-
-
Editor's Choice
Abstract
BACKGROUND AND AIM Although acute upper gastrointestinal bleeding (UGIB) can lead to anemia, evidence regarding the effects of oral iron supplementation on UGIB-induced anemia following discharge remains lacking. The present study aimed to investigate the effects of oral iron supplementation on hemoglobin response and iron storage in patients with anemia secondary to nonvariceal UGIB. METHODS This randomized controlled trial included 151 patients with nonvariceal UGIB who had anemia at discharge. Patients were assigned to a 1:1 block in which they were either administered 6 weeks of 600 mg/d oral ferrous fumarate (treatment group, n=77) or treated without iron supplementation (control group, n=74). The primary outcome was composite hemoglobin response (hemoglobin elevation greater than 2 g/dL or no anemia at the end of treatment [EOT]). RESULTS The proportion of patients achieving composite hemoglobin response was greater in the treatment group than in the control group (72.7% vs. 45.9%; adjusted risk ratio [RR], 2.980; p=0.004). At EOT, the percentage change in the hemoglobin level (34.2 ± 24.8 % vs. 19.4 ± 19.9 %; adjusted coefficient, 11.543; p<0.001) was significantly higher in the treatment group than in the control group; however, the proportions of patients with a serum ferritin level <30 μg/L and a transferrin saturation <16% were lower in the treatment group (all p<0.05). No significant differences in treatment-associated adverse effects and adherence rates were observed between the groups. CONCLUSIONS Oral iron supplementation exerts beneficial effects on anemia and iron storage following nonvariceal UGIB without significantly impacting rates of adverse effects or adherence. CLINICAL TRIAL REGISTRATION TCTR20190225002.
PICO Summary
Population
Patients with anaemia secondary to nonvariceal upper gastrointestinal bleeding (n= 151).
Intervention
Six weeks of 600 mg/d oral ferrous fumarate (treatment group, n= 77).
Comparison
No iron supplementation (control group, n= 74).
Outcome
The proportion of patients achieving composite haemoglobin response was greater in the treatment group than in the control group (72.7% vs. 45.9%; adjusted risk ratio [RR], 2.980). At end of treatment, the percentage change in the haemoglobin level (34.2 ± 24.8 % vs. 19.4 ± 19.9 %; adjusted coefficient, 11.543) was significantly higher in the treatment group than in the control group; however, the proportions of patients with a serum ferritin level <30 μg/L and a transferrin saturation <16% were lower in the treatment group. No significant differences in treatment-associated adverse effects and adherence rates were observed between the groups.
-
4.
Thalidomide for Recurrent Bleeding Due to Small-Intestinal Angiodysplasia
Chen, H., Wu, S., Tang, M., Zhao, R., Zhang, Q., Dai, Z., Gao, Y., Yang, S., Li, Z., Du, Y., et al
The New England journal of medicine. 2023;389(18):1649-1659
-
-
-
-
Editor's Choice
Abstract
BACKGROUND Recurrent bleeding from the small intestine accounts for 5 to 10% of cases of gastrointestinal bleeding and remains a therapeutic challenge. Thalidomide has been evaluated for the treatment of recurrent bleeding due to small-intestinal angiodysplasia (SIA), but confirmatory trials are lacking. METHODS We conducted a multicenter, double-blind, randomized, placebo-controlled trial to investigate the efficacy and safety of thalidomide for the treatment of recurrent bleeding due to SIA. Eligible patients with recurrent bleeding (at least four episodes of bleeding during the previous year) due to SIA were randomly assigned to receive thalidomide at an oral daily dose of 100 mg or 50 mg or placebo for 4 months. Patients were followed for at least 1 year after the end of the 4-month treatment period. The primary end point was effective response, which was defined as a reduction of at least 50% in the number of bleeding episodes that occurred during the year after the end of thalidomide treatment as compared with the number that occurred during the year before treatment. Key secondary end points were cessation of bleeding without rebleeding, blood transfusion, hospitalization because of bleeding, duration of bleeding, and hemoglobin levels. RESULTS Overall, 150 patients underwent randomization: 51 to the 100-mg thalidomide group, 49 to the 50-mg thalidomide group, and 50 to the placebo group. The percentages of patients with an effective response in the 100-mg thalidomide group, 50-mg thalidomide group, and placebo group were 68.6%, 51.0%, and 16.0%, respectively (P<0.001 for simultaneous comparison across the three groups). The results of the analyses of the secondary end points supported those of the primary end point. Adverse events were more common in the thalidomide groups than in the placebo group overall; specific events included constipation, somnolence, limb numbness, peripheral edema, dizziness, and elevated liver-enzyme levels. CONCLUSIONS In this placebo-controlled trial, treatment with thalidomide resulted in a reduction in bleeding in patients with recurrent bleeding due to SIA. (Funded by the National Natural Science Foundation of China and the Shanghai Municipal Education Commission, Gaofeng Clinical Medicine; ClinicalTrials.gov number, NCT02707484.).
PICO Summary
Population
Adult patients with recurrent bleeding due to small-intestinal angiodysplasia (n= 150).
Intervention
Thalidomide at an oral daily dose of 100 mg (n= 51).
Comparison
Thalidomide at an oral daily dose of 50 mg (n= 49). Placebo (n= 50).
Outcome
Patients were followed for at least 1 year after the end of the 4-month treatment period. The primary end point was effective response, which was defined as a reduction of at least 50% in the number of bleeding episodes that occurred during the year after the end of thalidomide treatment as compared with the number that occurred during the year before treatment. The percentages of patients with an effective response in the 100-mg thalidomide group, 50-mg thalidomide group, and placebo group were 68.6%, 51.0%, and 16.0%, respectively. The results of the analyses of the secondary end points supported those of the primary end point. Adverse events were more common in the thalidomide groups than in the placebo group overall; specific events included constipation, somnolence, limb numbness, peripheral edema, dizziness, and elevated liver-enzyme levels.
-
5.
Tranexamic acid for gastrointestinal bleeding: can a reduction in the risk of death be discounted? A systematic review and meta-analysis of individual patient data from 64 724 bleeding patients
Ker, K., Mansukhani, R., Shakur-Still, H., Arribas, M., Beaumont, D., Roberts, I.
BMJ open. 2023;13(2):e059982
Abstract
OBJECTIVES HALT-IT was an international, randomised trial which assessed the effects of tranexamic acid (TXA) in 12 009 patients with gastrointestinal (GI) bleeding. The results found no evidence that TXA reduces death. It is widely accepted that results of trials should be interpreted in the context of other relevant evidence. We conducted a systematic review and individual patient data (IPD) meta-analysis to assess if the results of HALT-IT are compatible with evidence for TXA in other bleeding conditions. DESIGN Systematic review and IPD meta-analysis of randomised trials involving ≥5000 patients assessing TXA for bleeding. We searched our Antifibrinolytics Trials Register on 1 November 2022. Two authors extracted data and assessed risk of bias. DATA SYNTHESIS We used a one-stage model to analyse IPD in a regression model stratified by trial. We assessed heterogeneity of the effect of TXA on death within 24 hours and vascular occlusive events (VOEs). RESULTS We included IPD for 64 724 patients from four trials involving patients with traumatic, obstetric and GI bleeding. Risk of bias was low. There was no evidence for heterogeneity between trials for the effect of TXA on death or for the effect of TXA on VOEs. TXA reduced the odds of death by 16% (OR=0.84, 95% CI: 0.78 to 0.91, p<0.0001; p-heterogeneity=0.40). In patients treated within 3 hours of bleeding onset, TXA reduced the odds of death by 20% (0.80, 0.73 to 0.88, p<0.0001; p-heterogeneity=0.16). TXA did not increase the odds of VOEs (0.94, 0.81 to 1.08, p for effect=0.36; p-heterogeneity=0.27). CONCLUSIONS There is no evidence for statistical heterogeneity between trials assessing the effect of TXA on death or VOEs in different bleeding conditions. When the HALT-IT results are considered in the context of other evidence, a reduction in the risk of death cannot be discounted. TRIAL REGISTRATION NUMBER PROSPERO CRD42019128260.Cite Now.
-
6.
Intravenous ferric carboxymaltose versus oral ferrous sulfate replacement in elderly patients after acute non-variceal gastrointestinal bleeding (FIERCE): protocol of a multicentre, open-label, randomised controlled trial
Teutsch, B., Váncsa, S., Farkas, N., Szakács, Z., Vörhendi, N., Boros, E., Szabó, I., Hágendorn, R., Alizadeh, H., Hegyi, P., et al
BMJ open. 2023;13(3):e063554
Abstract
INTRODUCTION Acute gastrointestinal bleeding (GIB) is a life-threatening emergency with a critical economic burden. As a result of bleeding, anaemia often requires intravenous or oral iron supplementation. Elderly patients are even more prone to untoward outcomes after hospital discharge if iron supplementation is inefficient. There is a gap in current guidelines on which supplementation route clinicians should choose. We aim to investigate the effect of one dose of intravenous iron therapy versus 3-month oral iron administration on anaemia in an elderly population. METHODS AND ANALYSIS The FIERCE study is an open-label, randomised controlled, two-armed trial. At least 48 hours after the acute non-variceal GIB treatment, patients will be recruited in participating centres. A random sequence generator will allocate the participants to group A (intravenous ferric carboxymaltose, 1000 mg) or group B (oral ferrous sulfate (FS), ca. 200 mg every day) with an allocation ratio of 1:1 on the day of the planned discharge from the hospital. Randomisation will be stratified for participating centres and the need for transfusion within the same hospitalisation before recruitment to the trial. Quality of life assessment, functional measurement and laboratory tests will be performed at baseline, 1 and 3 months±7 days after enrolment to the trial. The primary endpoint is a composite endpoint, including all-cause mortality, anaemia-associated unplanned emergency visit and anaemia-associated unplanned hospital admission within 3 months of enrolment in the trial. ETHICS AND DISSEMINATION The study has been approved by the relevant organisation, the Scientific and Research Ethics Committee of the Hungarian Medical Research Council (46395-5/2021/EÜIG). We will disseminate our results to the medical community and will publish our results in peer-reviewed journals. TRIAL REGISTRATION The trial has been registered at ClinicalTrials.gov (NCT05060731).
-
7.
Ferric carboxymaltose versus ferrous fumarate in anemic children with inflammatory bowel disease: the POPEYE randomized controlled clinical trial
Bevers N, Van de Vijver E, Aliu A, Ardabili AR, Rosias P, Stapelbroek J, Maartens IAB, van de Feen C, Escher JC, Oudshoorn A, et al
The Journal of pediatrics. 2022
-
-
-
Free full text
-
Full text
-
Editor's Choice
Abstract
OBJECTIVE To determine whether intravenous (IV) or oral iron suppletion is superior in improving physical fitness in anemic children with inflammatory bowel disease (IBD). STUDY DESIGN We conducted a clinical trial at 11 centers. Children aged 8 to 18 with IBD and anemia (defined as hemoglobin (Hb) z-score < -2) were randomly assigned to a single IV dose of ferric carboxymaltose or 12 weeks of oral ferrous fumarate. Primary endpoint was the change in 6-minute walking distance (6MWD) from baseline, expressed as z-score. Secondary outcome was a change in Hb z-score from baseline. RESULTS We randomized 64 patients (33 IV iron; 31 oral iron) and followed them for 6 months. One month after the start of iron therapy, the 6MWD z-score of patients in the IV group had increased by 0.71 compared with -0.11 in the oral group (P=0.01). At 3- and 6-months follow-up, no significant differences in 6MWD z-scores were observed. Hb z-scores gradually increased in both groups and the rate of increase was not different between groups at 1, 3 and 6 months after initiation of iron therapy (overall P=0.97). CONCLUSION In this trial involving anemic children with IBD, a single dose of IV ferric carboxymaltose was superior to oral ferrous fumarate with respect to quick improvement of physical fitness. At 3 and 6 months after initiation of therapy, no differences were discovered between oral or IV therapy. The increase of Hb over time was comparable in both treatment groups. TRIAL REGISTRATION NTR4487 [Netherlands Trial Registry].
PICO Summary
Population
Children with anaemia and inflammatory bowel disease, enrolled in the POPEYE trial, in 9 Dutch and 2 Belgian hospitals (n= 64).
Intervention
Single intravenous dose of ferric carboxymaltose (IV group), (n= 33).
Comparison
12 weeks of oral ferrous fumarate (oral group), (n= 31).
Outcome
The primary endpoint was the change in 6-minute walking distance (6MWD) from baseline, expressed as z-score. The secondary outcome was a change in Hb z-score from baseline. One month after the start of iron therapy, the 6MWD z-score of patients in the IV group had increased by 0.71 compared with -0.11 in the oral group. At 3- and 6- months follow-up, no significant differences in 6MWD z-scores were observed. Hb z-scores gradually increased in both groups and the rate of increase was not different between groups at 1, 3 and 6 months after initiation of iron therapy.
-
8.
Clinical efficacy of norepinephrine combined with cimetidine in treatment of neonatal upper gastrointestinal hemorrhage and its adverse reactions
Dong X, Li H, Zhu T
Pakistan journal of medical sciences. 2022;38(8):2215-2219
Abstract
OBJECTIVES To investigate the clinical efficacy of norepinephrine combined with cimetidine in the treatment of neonatal upper gastrointestinal hemorrhage and its adverse reactions. METHODS A total of 68 cases of neonatal upper gastrointestinal hemorrhage in Huangshi Maternal and Child Health Care Hospital from please mention dates October 2018 to February 2020 were selected and randomly divided into treatment group and control group by coin tossing, with 34 infants in each group. The control group received conventional therapy, and the treatment group was additionally treated with norepinephrine combined with cimetidine. The efficacy and safety were compared between the two groups. RESULTS The time when the bleeding stops, the time of fecal occult blood turning negative and hospital stay of the treatment group were shorter than those of the control group (P < 0.05). Superoxide dismutase (SOD) level increased while malondialdehyde (MDA) level decreased in both groups after treatment compared with those before treatment (P < 0.05). After treatment, the SOD level was higher while the MDA level was lower in the treatment group than those in the control group (P < 0.05). The effective rate of the treatment group was higher than that of the control group (P < 0.05). However, no significance was found in adverse reactions between the two groups (P > 0.05). CONCLUSION Norepinephrine combined with cimetidine in the treatment of neonatal upper gastrointestinal hemorrhage can shorten the recovery time of symptoms, improve efficacy and reduce stress reaction. It is safe, effective and worthy of use in clinical practice.
-
9.
An extended 36-week oral esomeprazole improved long-term recurrent peptic ulcer bleeding in patients at high risk of rebleeding
Chiang HC, Yang EH, Hu HM, Chen WY, Chang WL, Wu CT, Wu DC, Sheu BS, Cheng HC
BMC gastroenterology. 2022;22(1):439
Abstract
BACKGROUND Patients with Rockall scores ≥6 have an increased risk of long-term peptic ulcer rebleeding. This study was aimed toward investigating whether an extended course of oral esomeprazole up to 1 year decreased ulcer rebleeding in such patients. METHODS We prospectively enrolled 120 patients with peptic ulcer bleeding and Rockall scores ≥6. After an initial 16-week oral proton pump inhibitor (PPI) treatment, patients were randomized to receive a 36-week course of oral twice-daily esomeprazole 20 mg (Group D, n = 60) or once-daily (Group S, n = 60). Thereafter, they were divided into the PPI-on-demand (n = 32) and PPI-discontinued (n = 77) subgroups. Our previous cohort with Rockall scores ≥6 served as the controls (Group C, n = 135); they received only an initial 8- to 16-week oral PPI. The primary and secondary outcomes were peptic ulcer rebleeding during the first year and the second year-and-thereafter, respectively. RESULTS For the primary outcome, groups D and S comprised a higher proportion of rebleeding-free than Group C (P = 0.008 and 0.03, log-rank test). The competing-risks regression analysis confirmed that extended PPI use and American Society of Anesthesiologists classification were independent factors contributing to the primary outcome. For the secondary outcome, PPI-on-demand had a borderline higher proportion of rebleeding-free than Group C (P = 0.07, log-rank test); however, only the Rockall score was the independent factor. CONCLUSIONS An extended 36-week course of oral esomeprazole 20 mg, twice- or once-daily for patients with Rockall scores ≥6 reduced ulcer rebleeding during the first year, but the effect needed to be further validated when PPIs were shifted to on-demand or discontinued thereafter (NCT02456012, 28/05/2015).
-
10.
Hypophosphataemia following ferric derisomaltose and ferric carboxymaltose in patients with iron deficiency anaemia due to inflammatory bowel disease (PHOSPHARE-IBD): a randomised clinical trial
Zoller H, Wolf M, Blumenstein I, Primas C, Lindgren S, Thomsen LL, Reinisch W, Iqbal T
Gut. 2022
-
-
-
Free full text
-
Full text
-
Editor's Choice
Abstract
OBJECTIVE Intravenous iron-a common treatment for anaemia and iron deficiency due to inflammatory bowel disease (IBD)-can cause hypophosphataemia. This trial compared the incidence of hypophosphataemia after treatment with ferric carboxymaltose (FCM) or ferric derisomaltose (FDI). DESIGN This randomised, double-blind, clinical trial was conducted at 20 outpatient hospital clinics in Europe (Austria, Denmark, Germany, Sweden, UK). Adults with IBD and iron deficiency anaemia (IDA) were randomised 1:1 to receive FCM or FDI at baseline and at Day 35 using identical haemoglobin- and weight-based dosing regimens. The primary outcome was the incidence of hypophosphataemia (serum phosphate <2.0 mg/dL) at any time from baseline to Day 35 in the safety analysis set (all patients who received ≥1 dose of study drug). Markers of mineral and bone homeostasis, and patient-reported fatigue scores, were measured. RESULTS A total of 156 patients were screened; 97 (49 FDI, 48 FCM) were included and treated. Incident hypophosphataemia occurred in 8.3% (4/48) FDI-treated patients and in 51.0% (25/49) FCM-treated patients (adjusted risk difference: -42.8% (95% CI -57.1% to -24.6%) p<0.0001). Both iron formulations corrected IDA. Patient-reported fatigue scores improved in both groups, but more slowly and to a lesser extent with FCM than FDI; slower improvement in fatigue was associated with greater decrease in phosphate concentration. CONCLUSION Despite comparably effective treatment of IDA, FCM caused a significantly higher rate of hypophosphataemia than FDI. Further studies are needed to address the longer-term clinical consequences of hypophosphataemia and to investigate mechanisms underpinning the differential effects of FCM and FDI on patient-reported fatigue.
PICO Summary
Population
Adults with inflammatory bowel disease and iron deficiency anaemia enrolled in the PHOSPHARE-IBD trial in five European countries (n= 97).
Intervention
Ferric carboxymaltose (FCM), (n= 48).
Comparison
Ferric derisomaltose (FDI), (n= 49).
Outcome
Incident hypophosphataemia occurred in 8.3% FDI-treated patients and in 51% FCM-treated patients (adjusted risk difference: -42.8% (95% CI -57.1% to -24.6%)). Both iron formulations corrected iron deficiency anaemia. Patient-reported fatigue scores improved in both groups, but more slowly and to a lesser extent with FCM than FDI; slower improvement in fatigue was associated with greater decrease in phosphate concentration.