Anaemia
Conditions
Keywords
Tranexamic acid, Antifibrinolytic, Anaemia, Menstrual health, Menstruation, Bleeding, Iron Deficiency
Brief summary
Anaemia is when the body does not have enough healthy red blood cells to carry oxygen. It is common in women because they lose blood every month during their periods. Anaemia can womwn make feel tired, weak, dizzy and out of breath. It can also make it harder to study, work or look after their family. If woman become pregnant with anaemia, it can cause problems for both mother and baby, such as early birth or heavy bleeding when giving birth. 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. 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. The global target, set in 2000, to halve the prevalence of anaemia in women of reproductive age by 2025 was not met. 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
DRUGPlacebo
Tablets
Sponsors
London School of Hygiene and Tropical Medicine
University of Dar es Salaam, Tanzania (Mbeya College of Health and Allied Sciences)
Coefficient Giving (Formerly Open Philanthropy)
Versailles Saint-Quentin-en-Yvelines University
Shifa Tameer-e-Millat University
University College Hospital, Ibadan
The Jon Moulton Charity Trust
University of Edinburgh
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Two-arm parallel design comparing tranexamic acid (TXA) versus placebo, with participants randomized in a 1:1 ratio.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult women aged 18 years and older. * Currently menstruating, with menstrual periods occurring at least every 38 days and lasting ≥2 days. * Anaemia at screening, defined as hemoglobin (Hb) \<120 g/L by point-of-care finger prick test. * Willing and able to provide informed consent. * Able to attend in-person follow-up visits during the trial period. Individuals with known thalassaemia and sickle cell disease are eligible to participate and take the trial treatment but will not be given standard of care iron supplementation unless it is prescribed by their own treating clinician. They will continue to receive their usual standard care.
Exclusion criteria
* Planning to get pregnant during the trial period * Already taking TXA * Known to have possible 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 |
|---|---|---|
| Proportion of Participants with Anaemia | From enrollment until after the 6th menstrual period but before the 7th, or within 9 months from randomization (±1 week), whichever occurs first. | Proportion of participants with hemoglobin (Hb) \<120 g/L, measured via venous blood samples at baseline and at the end of the intervention period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Haemoglobin (Hb) concentration | From enrollment until after the 6th menstrual period but before the 7th, or within 9 months from randomization (±1 week), whichever occurs first. | Hb measured on venous blood at baseline and end of treatment/ early withdrawal |
| Severity of anaemia | From enrollment until after the 6th menstrual period but before the 7th, or within 9 months from randomization (±1 week), 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 | From enrollment until after the 6th menstrual period but before the 7th, or within 9 months from randomization (±1 week), whichever occurs first. | Serum ferritin (from venous blood sample) and CRP-adjusted ferritin (see below, under C-reactive protein) measured at baseline and end of the intervention period; we will report change in iron status from baseline |
| Iron deficiency | From enrollment until after the 6th menstrual period but before the 7th, or within 9 months from randomization (±1 week), 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); we will report change in iron status from baseline Note: CRP-adjusted ferritin (see below); |
| C-reactive protein (CRP) | From enrollment until after the 6th menstrual period but before the 7th, or within 9 months from randomization (±1 week), whichever occurs first. | Measured to adjust ferritin values. 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 |
| Iron-deficiency anaemia | From enrollment until after the 6th menstrual period but before the 7th, or within 9 months from randomization (±1 week), 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) |
| Menstrual blood loss | Throughout the trial from enrollment through the final visit (after 6th menstrual period or within 9 months from randomization). | Self-reported number of menstrual products used |
| Perceived change in menstrual blood loss | Throughout the trial from enrollment through the final visit (after 6th menstrual period or within 9 months from randomization). | Participant's subjective assessment of intensity and impact of menstrual bleeding, using visual analogue scales (HMB-VAS), assessed at baseline and final visit |
| Degree of effect of menstrual bleeding on health-related Quality of Life | Throughout the trial from enrollment through the final visit (after 6th menstrual period or within 9 months from randomization). | 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.) |
| Mean Menstrual Period Duration | Throughout the trial from enrollment through the final visit (after 6th menstrual period or within 9 months from randomization). | Evaluated longitudinally via participant daily diary logs to assess changes in bleeding length across treatment cycles. |
| Change From Baseline in Menstrual Pain Severity Score | Throughout the trial from enrollment through the final visit (after 6th menstrual period or within 9 months from randomization). | Measured on a standard 0 to 10 numerical rating scale inside the participant diary, where 0 represents no pain and 10 represents the worst imaginable period pain. |
| Mean Hemoglobin (Hb) Concentration at Final Visit | Throughout the trial from enrollment through the final visit (after 6th menstrual period or within 9 months from randomization). | Analysed via laboratory venous blood collection to document efficacy on maternal anemia resolution. |
| Mean Serum Ferritin Concentration at Final Visit | Throughout the trial from enrollment through the final visit (after 6th menstrual period or within 9 months from randomisation). | Evaluated via venous blood sample to track maternal iron storage status. Ferritin values will be adjusted against C-reactive protein levels within the final Statistical Analysis Plan (SAP) to prevent acute inflammation from masking underlying iron depletion. |
| Mean Systolic and Diastolic Blood Pressure at Study Completion | Throughout the trial from enrollment through the final visit (after 6th menstrual period or within 9 months from randomization). | Monitored via a standard automated digital sphygmomanometer during in-person clinical visits. |
| Mean Heart Rate at Study Completion | Throughout the trial from enrollment through the final visit (after 6th menstrual period or within 9 months from randomisation) | Pulse rates monitored on-site alongside vital sign collections. |
Countries
Nigeria, Pakistan, Tanzania
Contacts
CONTACTProfessor Ian Roberts
PRINCIPAL_INVESTIGATORProfessor Ian Roberts
London School of Hygiene and Tropical Medicine (Clinical Trials Unit)
CONTACTEni Balogun
Outcome results
None listed