Ferritin-guided iron supplementation as an alternative or complement to prolonged blood donation intervals (FORTE): a double-blind, randomised, controlled trial.

Oral iron supplementation is known to shorten post-donation iron recovery time and could serve as an alternative to extended donation intervals.

口服铁剂补充已知可以缩短献血后的铁恢复时间，并且可以作为一种延长献血间隔的替代方法。

We aimed to evaluate the effect of different iron supplementation protocols on ferritin and haemoglobin levels, gastrointestinal side-effects, iron deficiency-related symptoms, and donor return compared with placebo supplementation.

我们旨在评估不同铁剂补充方案对铁蛋白和血红蛋白水平、胃肠道副作用、铁缺乏相关症状以及与安慰剂补充相比的献血者回访的影响。

Methods

In this double-blind, randomised, placebo-controlledtrial conducted at seven of Sanquin's blood donation centres in The Netherlands, donors aged 18-80 years with ferritin levels equal to or less than 30 μg/L were randomly allocated to one of six study groups, using block randomisation in equal numbers by sex and age.

在这项在荷兰Sanquin的七家血液捐赠中心进行的双盲、随机、安慰剂对照试验中，年龄在18-80岁之间、铁蛋白水平等于或低于30 μg/L的捐赠者被随机分配到六个研究组中的一个，通过性别和年龄的等量分块随机化。

Donors were instructed to adhere to a ferrous bisglycinate supplementation protocol for 56 days, taking capsules containing 0 mg (placebo), 30 mg, or 60 mg of elemental iron, either daily or on alternate days.

供体被指导遵循为期56天的富马酸亚铁补充方案，服用含有0毫克（安慰剂）、30毫克或60毫克元素铁的胶囊，可以每天或隔天服用。

The primary outcomes were presence of iron deficiency (<15 μg/L), low ferritin (15-30 μg/L), and low haemoglobin (≤135 g/L for male donors and ≤125 g/L for female donors) at 56 days' follow-up.

主要结果是在56天随访时铁缺乏（<15 μg/L）、低铁蛋白（15-30 μg/L）和低血红蛋白（男性供体≤135 g/L，女性供体≤125 g/L）的存在情况。

Analyses were conducted using an intention-to-treatapproach.

分析采用意向治疗分析方法进行。

This trial is registered in the Dutch trial registry (NL7328.018.20) and is complete.

该试验已在荷兰试验注册处注册（注册号NL7328.018.20），且已结束。

Results

Between Aug 1, 2021, and Jan 15, 2023, 830 donors (464 [56%] female donors and 366 [44%] male donors; 789 [95%] of Dutch origin and 26 [3%] of non-Dutch origin) had low ferritin and were included in the trial. At 56 days, 55 (51%) of 108 participants in the placebo daily group, 58 (49%) of 119 participants in the placebo alternate day group, 11 (10%) of 107 participants in the 30 mg daily group, eight (7%) of 112 participants in the 30 mg alternate day group, one (1%) of 114 participants in the 60 mg daily group, and four (4%) of 110 participants in the 60 mg alternate day group presented with iron deficiency.

2021年8月1日至2023年1月15日期间，共有830名供体（女性供体464名[56%]，男性供体366名[44%]；荷兰裔供体789名[95%]，非荷兰裔供体26名[3%]）因铁蛋白低而被纳入试验。在第56天时，安慰剂每日组的108名参与者中有55名（51%）出现铁缺乏，安慰剂隔日组的119名参与者中有58名（49%）出现铁缺乏，30毫克每日组的107名参与者中有11名（10%）出现铁缺乏，30毫克隔日组的112名参与者中有8名（7%）出现铁缺乏，60毫克每日组的114名参与者中有1名（1%）出现铁缺乏，60毫克隔日组的110名参与者中有4名（4%）出现铁缺乏。

Compared with daily placebo, all iron supplementation groups exhibited similar significantly lower odds of iron deficiency at 56 days, with odds ratios (ORs) of 0·62 (95% CI 0·56-0·68) for 30 mg daily, 0·63 (0·57-0·70) for 30 mg alternative days, 0·60 (0·55-0·66) for 60 mg daily, and 0·65 (0·59-0·72) for 60 mg on alternative days.

与每日安慰剂相比，所有铁补充组在第56天时铁缺乏的几率显著降低，其中30毫克每日组的优势比（OR）为0.62（95%置信区间0.56-0.68），30毫克隔日组为0.63（0.57-0.70），60毫克每日组为0.60（0.55-0.66），60毫克隔日组为0.65（0.59-0.72）。

For low ferritin, 0·70 (0·63-0·78) for 30 mg daily, 0·82 (0·74-0·91) for 30 mg on alternative days, 0·52 (0·47-0·57) for 60 mg daily, and 0·61 (0·55-0·68) for 60 mg on alternate days.

对于低铁蛋白水平，每日30毫克的比值比为0.70（95%置信区间0.63-0.78），隔日30毫克为0.82（95%置信区间0.74-0.91），每日60毫克为0.52（95%置信区间0.47-0.57），隔日60毫克为0.61（95%置信区间0.55-0.68）。

For low haemoglobin, the ORs were 0·78 (0·67-0·91) for 30 mg daily, 0·80 (0·68-0·93) for 30 mg on alternative days, 0·75 (0·64-0·86) for 60 mg daily, and 0·77 (0·66-0·90) for 60 mg alternative days.

对于低血红蛋白水平，每日30毫克的比值比为0.78（95%置信区间0.67-0.91），隔日30毫克为0.80（95%置信区间0.68-0.93），每日60毫克为0.75（95%置信区间0.64-0.86），隔日60毫克为0.77（95%置信区间0.66-0.90）。

Adverse events were reported in two participants-one event, an increase in migraines, was considered potentially related to the study intervention, but the other (a death) was deemed unrelated.

两名参与者报告了不良事件-其中一起事件，偏头痛的增加，被认为可能与研究干预有关，但另一事件（一起死亡）被认为无关。

interpretation

In regular donors with low ferritin, iron supplementation-60 mg taken daily, in particular-effectively mitigates iron deficiency, low ferritin, and low haemoglobin.

在铁蛋白水平低的定期供血者中，铁补充疗法-特别是每天服用60毫克-有效地缓解了铁缺乏、低铁蛋白和低血红蛋白。

Iron supplementation is an effective alternative or supplement to extended donation intervals for whole-blood donors with low ferritin levels.

对于铁蛋白水平低的全血献血者，铁剂补充是延长献血间隔的有效替代或补充方法。

funding

Sanquin Blood Supply Foundation.

Sanquin血液供应基金会。

translation

For the Dutch translation of the abstract see Supplementary Materials section.

摘要的荷兰语翻译请参见补充材料部分。