Lancet
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Randomized Controlled Trial Multicenter Study
Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial.
Why is this a landmark trial?
Three reasons:
- Clinical significance of the findings: reducing maternal mortality.
- Relevance to much of world's population, in particular to low resource settings where post-partum haemorrhage (PPH) is disproportionately burdensome.
- Quality – a massive, double-blinded randomised controlled trial.
So, what did they do?
They randomised 20,060 women with PPH to receive either 1g of tranexamic acid (100mg/min slow IV) or placebo, across 21 countries and 193 hospitals. Although only 569 (2.8%) patients were from a high resource country (UK).
What did they find?
Mortality due to haemorrhage was reduced by almost 20% (RR 0.81, NNT 267) after receiving tranexamic acid (TXA), and by 30% (RR 0.69) when given within 3 hours of birth.
Hysterectomies were not reduced by TXA use. There was no increased risk of thromboembolic events.
Be smart
While on the surface this suggests we should move to routine use of TXA in managing all PPH, the risk of PPH-death in most high resource countries is relatively low. 99% of all PPH deaths are in low resource countries.
In the WOMAN trial the risk of death in the placebo group was 1.9%. In contrast the latest maternal mortality data from MBRACE-UK (2014-16) reports 0.78 haemorrhage-deaths per 100,000 maternities, which using a conservative 5% PPH incidence (depending on definition), yields a PPH-mortality risk of 0.016% – 100x less than the study population.
Thus in a high resource setting the TXA NNT to avoiding one maternal death is generously at least 20,000 PPH cases.
In high resource settings, TXA use should be considered second-line therapy in managing severe PPH when other measures are inadequate. In low resource settings where maternal PPH mortality Is high, TXA reduces maternal mortality and should be routinely used.
Context is everything.
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Randomized Controlled Trial
Targeted-release budesonide versus placebo in patients with IgA nephropathy (NEFIGAN): a double-blind, randomised, placebo-controlled phase 2b trial.
IgA nephropathy is thought to be associated with mucosal immune system dysfunction, which manifests as renal IgA deposition that leads to impairment and end-stage renal disease in 20-40% of patients within 10-20 years. In this trial (NEFIGAN) we aimed to assess safety and efficacy of a novel targeted-release formulation of budesonide (TRF-budesonide), designed to deliver the drug to the distal ileum in patients with IgA nephropathy. ⋯ Pharmalink AB.
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Randomized Controlled Trial Multicenter Study Comparative Study
First-line rituximab combined with short-term prednisone versus prednisone alone for the treatment of pemphigus (Ritux 3): a prospective, multicentre, parallel-group, open-label randomised trial.
High doses of corticosteroids are considered the standard treatment for pemphigus. Because long-term corticosteroid treatment can cause severe and even life-threatening side-effects in patients with this disease, we assessed whether first-line use of rituximab as adjuvant therapy could improve the proportion of patients achieving complete remission off-therapy, compared with corticosteroid treatment alone, while decreasing treatment side-effects of corticosteroids. ⋯ French Ministry of Health, French Society of Dermatology, Roche.
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Randomized Controlled Trial Comparative Study
Single inhaler extrafine triple therapy versus long-acting muscarinic antagonist therapy for chronic obstructive pulmonary disease (TRINITY): a double-blind, parallel group, randomised controlled trial.
Limited data are available for the efficacy of triple therapy with two long-acting bronchodilators and an inhaled corticosteroid in chronic obstructive pulmonary disease (COPD). We compared treatment with extrafine beclometasone dipropionate, formoterol fumarate, and glycopyrronium bromide (BDP/FF/GB; fixed triple) with tiotropium, and BDP/FF plus tiotropium (open triple). ⋯ Chiesi Farmaceutici SpA.
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Randomized Controlled Trial Multicenter Study
Clinically significant bleeding with low-dose rivaroxaban versus aspirin, in addition to P2Y12 inhibition, in acute coronary syndromes (GEMINI-ACS-1): a double-blind, multicentre, randomised trial.
Dual antiplatelet therapy (DAPT), aspirin plus a P2Y12 inhibitor, is the standard antithrombotic treatment following acute coronary syndromes. The factor Xa inhibitor rivaroxaban reduced mortality and ischaemic events when added to DAPT, but caused increased bleeding. The safety of a dual pathway antithrombotic therapy approach combining low-dose rivaroxaban (in place of aspirin) with a P2Y12 inhibitor has not been assesssed in acute coronary syndromes. We aimed to assess rivaroxaban 2·5 mg twice daily versus aspirin 100 mg daily, in addition to clopidogrel or ticagrelor (chosen at investigator discretion before randomisation), for patients with acute coronary syndromes started within 10 days after presentation and continued for 6-12 months. ⋯ Janssen Research & Development and Bayer AG.