Tranexamic Acid for Anaemia Trial

Phase 3

Not yet recruiting

• Conditions: Anemia
• Interventions: Drug: Tranexamic Acid 500 MG; Other: Matched placebo

• Registration Number: NCT06519422
• Lead Sponsor: London School of Hygiene and Tropical Medicine

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.

Study Timeline

• Status Verified: 2024-07
• Study First Submitted: 2024-07-11
• Study First Submitted QC: 2024-07-19
• Last Update Submitted: 2024-07-19
• Study First Posted: 2024-07-25
• Last Update Posted: 2024-07-25
• Study Start: 2025-09
• Primary Completion: 2028-08
• Study Completion: 2028-09

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: Female
• Target Recruitment: 4000

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.)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Tranexamic acid (TXA)	Tranexamic Acid 500 MG	Tranexamic acid 1 gram (2x 500 mg) orally taken three times a day from the first to the last day of the menstrual period for up to 5 days, for 3 successive periods.
Placebo	Matched placebo	Matched placebo tablets taken three times a day from the first to the last day of the menstrual period for up to 5 days, for 3 successive periods.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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
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
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 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)
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")
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
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
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.)
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)
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')