Anemia
Conditions
Keywords
Tranexamic acid, Antifibrinolytic, Anaemia, Menstrual health, Menstruation, Bleeding
Brief summary
Anaemia is a common health problem in women. It is often due to iron deficiency. Anaemia is a particular problem during pregnancy and is bad for the mother and baby. It is best to treat anaemia in young women well before they get pregnant. Doctors treat anaemia with iron and vitamins. But some people get side effects when taking iron tablets and so they stop taking them. Heavy menstrual periods are a common cause of iron deficiency and even if women do take iron, because they lose so much iron in their periods, they still become iron deficient. Tranexamic acid (TXA) is a medicine used to treat heavy periods. The investigators of this study would like to find out if taking TXA with the usual iron and vitamin supplements is better at treating anaemia than taking iron and vitamin supplements alone. (Lay Summary)
Detailed description
World-wide, half a billion women of reproductive age are anaemic. Anaemia has major health consequences for pregnant women and their babies. Anaemia increases the risk of ante-partum haemorrhage, prematurity, stillbirth, neonatal death, post-partum haemorrhage and maternal death. Early intervention to reduce the risk of anaemia before pregnancy offers the potential to reduce adverse maternal and birth outcomes and improve well-being across the reproductive life course. Unfortunately, global efforts to reduce anaemia prevalence by 2025 are far off track. Anaemia worsens bleeding through multiple biological mechanisms. Anaemia increases blood flow from bleeding vessels due to reduced blood viscosity and anaemic blood clots are more susceptible to fibrinolysis. Although iron and multivitamin replacement is the mainstay of anaemia treatment, iron stores in young women depend more on menstrual iron loss than on dietary intake. Because anaemia worsens bleeding, women with anaemia have heavier menstrual periods than if they were not anaemic. For this reason, offering iron replacement without reducing menstrual iron loss may be inefficient. The antifibrinolytic tranexamic acid (TXA) reduces menstrual bleeding by preventing blood clot breakdown. The investigators propose that giving TXA with iron and vitamin replacement will be more effective in treating anaemia than iron and vitamin replacement alone.
Interventions
Tablets
OTHERMatched placebo
Matched placebo tablets (inactive ingredients only, including microcrystalline cellulose, magnesium stearate BP and lactose)
Sponsors
The Jon Moulton Charity Trust
London School of Hygiene and Tropical Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult women (aged 18 years and older) * Having menstrual periods every 21 to 38 days that last 2 to 9 days * Having anaemia (Hb \< 120 g/L) according to point-of-care finger prick screening test * Willing to provide informed consent and able to attend study visits during the trial period (Individuals with known thalassaemia are eligible to participate and take the trial treatment but will not receive standard of care iron supplementation. They will continue to receive their standard care.)
Exclusion criteria
* Planning to get pregnant during trial period * Already taking TXA * Known to have contraindications to TXA treatment (including allergy to TXA or its excipients, renal impairment, active thromboembolic disease, history of venous or arterial thrombosis, history of convulsion.)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Anaemia | After the 3rd and before the 4th menstrual period or by 6 months from baseline, whichever occurs first. | The proportion of participants with anaemia, defined as Haemoglobin (Hb) \< 120 g/L (measured on venous blood) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Severity of anaemia | After the 3rd and before the 4th menstrual period or by 6 months from baseline, whichever occurs first. | Mild Anaemia (Hb=110-119 g/L); Moderate Anaemia (Hb=80-109 g/L); Severe Anaemia (Hb \< 80 g/L); Hb measured on venous blood |
| Ferritin | After the 3rd and before the 4th menstrual period or by 6 months from baseline, whichever occurs first. | Serum ferritin (from venous blood sample) and CRP-adjusted ferritin (see below, under C-reactive protein) |
| Iron deficiency | After the 3rd and before the 4th menstrual period or by 6 months from baseline, whichever occurs first. | Iron deficiency defined as ferritin \<15 ug/L (WHO definition) and defined as ferritin \<30 ug/L, (new clinical consensus); Serum ferritin from venous blood sample; CRP-adjusted ferritin (see below, under C-reactive protein) Note: CRP-adjusted ferritin (see below) |
| C-reactive protein (CRP) | After the 3rd and before the 4th menstrual period or by 6 months from baseline, whichever occurs first. | The Statistical Analysis Plan (SAP) will include details on how ferritin values will be corrected by taking into account CRP levels (inflammation marker), because normal ferritin concentrations may mask an iron deficient state if inflammation is present |
| Haemoglobin (Hb) concentration | After the 3rd and before the 4th menstrual period or by 6 months from baseline, whichever occurs first. | Hb measured on venous blood |
| Menstrual blood loss | During 3 menstrual periods (on average about 3 months, but no longer than 6 months from baseline) | Blood loss assessed semi-quantitatively by pictorial blood assessment chart (PBAC), adapted from Higham et al (1990), DOI: 10.1111/j.1471-0528.1990.tb16249.x |
| Perceived change in menstrual blood loss | After the 3rd and before the 4th menstrual period or by 6 months from baseline, whichever occurs first. | Participant's subjective assessment of change in menstrual bleeding from baseline, e.g. expressed on a Likert scale ('greatly improved' to 'much worse') |
| Degree of effect of menstrual bleeding on health-related Quality of Life | After the 3rd and before the 4th menstrual period or by 6 months from baseline, whichever occurs first. | SAMANTA scale (ref: Calaf, 2020, DOI: 10.1089/jwh.2018.7446 and Sinharoy 2023, DOI: 10.1016/S2214-109X(23)00416-3; Affirmative answers to two questions ('experiencing menstrual bleeding for \>7 days per month' and 'being bothered by menstruation due to its Abundance') each receive 3 points, while affirmative answers to all other questions each receive 1 point ('≥3 days of heavier bleeding', 'blood spotting on clothes at night', 'worried about staining furniture', 'avoid some activities because of the need to change menstrual materials'). These values are summed, resulting in a potential range of values for the heavy menstrual bleeding score from 0 to 10.) |
| Flooding | During 3 menstrual periods (on average about 3 months, but no longer than 6 months from baseline) | 'Flooding' experienced during menstrual period (provisionally defined by Cooper 2013, DOI: 10.1111/1471-0528.17473, as sudden overwhelming blood loss that exceeds the saturation of the menstrual products being used) |
| Iron-deficiency anaemia | After the 3rd and before the 4th menstrual period or by 6 months from baseline, whichever occurs first. | The proportion of participants with iron-deficiency anaemia, defined as presence of both anaemia (Hb\<120 g/L) plus iron deficiency (ferritin \<15 ug/L AND/OR \<30 ug/L), measured as detailed above (using CRP-adjusted ferritin levels, as explained above) |
Contacts
Primary ContactDr Sima Berendes
Backup ContactProfessor Ian Roberts
Outcome results
None listed