100 YILLIK İLAÇ ETKİSİZ BULUNDU. PARASETAMOL BEL AĞRISINDA PLASEBODAN FARKSIZ!

klinik farmakoloji dosyası
Haber

120 Senelik ilaç etkisiz çıktı
1883 te keşfedilen ABD de 1950 de piyasya verilen ve dünyada milyonlarca kutu satan ve aşağı yukarı 50 milyar dolar ciroya sahip PARASETAMOL (ASETAMİNOFEN) keşfinden 120 yıl sonra yapılan ilk (!) ciddi randomize, plasebo kontrollu klinik araştırmada, bel ağrısında tamamen etkisiz bulundu.
Avusturalya Sidneyde 1652 bel ağrısı hastasında yapılan araştırmada hastalar 3 eşit gruba ayrılarak, birinci gruba günde üç kere toplam 4 gram, ikinci gruba ihtiyaç duyduğunda kullanmak üzere günde maksimum 4 gram ve üçüncü gruba ise plasebo verilmiştir. Bu çalışmaya ‘The Paracetamol for Low-Back Pain Study (PACE)’ ismi verilmiş. Çalışma 235 birici basamak sağlık merkezinde 11 Kasım 2009-5 mart 2013 tarihlerinde yapılmıştır. Çalışma sonunda parasetamol grupları ile plasebo grubu arasında ağrı, maluliyet, fonksiyon, global semptom değişikliği, uyku ve yaşam kalitesi yönünden herhangi bir fark bulunamamıştır. İhtiyaç duyduğunda parasetamol kullanan hastalar 17, plasebo alan hastalar 16 günde iyileşmişler.
Yazarlar, bir çok ulusal klinik tedavi rehberlerinde akut aşağı bel ağrılarında ilk tercih olarak tavsiye edilen parasetamolün hiç bir ciddi klinik araştırmaya dayanmadığını, bunun ampirik bilgilerle kullanıldığını belirtmişlerdir. Buna mukabil NSAID lerin (bilindiği gibi parasetamolün herhangi bir antiinflamatuar etkisi yoktur) aşağı bel ağrısında etkili olduğunun çeşitli klinik çalışmalarda gösterilmiştir.
The Lancet, Early Online Publication, 24 July 2014
Efficacy of paracetamol for acute low-back pain: a double-blind, randomised controlled trial
Dr Christopher M Williams PhD a e , Prof Christopher G Maher PhD a, Prof Jane Latimer a, Prof Andrew J McLachlan PhD b, Mark J Hancock PhD c, Prof Richard O Day MD d, Chung-Wei Christine Lin PhD a

Background
Regular paracetamol is the recommended first-line analgesic for acute low-back pain; however, no high-quality evidence supports this recommendation. We aimed to assess the efficacy of paracetamol taken regularly or as-needed to improve time to recovery from pain, compared with placebo, in patients with low-back pain.
Methods
We did a multicentre, double-dummy, randomised, placebo controlled trial across 235 primary care centres in Sydney, Australia, from Nov 11, 2009, to March 5, 2013. We randomly allocated patients with acute low-back pain in a 1:1:1 ratio to receive up to 4 weeks of regular doses of paracetamol (three times per day; equivalent to 3990 mg paracetamol per day), as-needed doses of paracetamol (taken when needed for pain relief; maximum 4000 mg paracetamol per day), or placebo. Randomisation was done according to a centralised randomisation schedule prepared by a researcher who was not involved in patient recruitment or data collection. Patients and staff at all sites were masked to treatment allocation. All participants received best-evidence advice and were followed up for 3 months. The primary outcome was time until recovery from low-back pain, with recovery defined as a pain score of 0 or 1 (on a 0—10 pain scale) sustained for 7 consecutive days. All data were analysed by intention to treat. This study is registered with the Australian and New Zealand Clinical Trial Registry, number ACTN 12609000966291.
Findings
550 participants were assigned to the regular group (550 analysed), 549 were assigned to the as-needed group (546 analysed), and 553 were assigned to the placebo group (547 analysed). Median time to recovery was 17 days (95% CI 14—19) in the regular group, 17 days (15—20) in the as-needed group, and 16 days (14—20) in the placebo group (regular vs placebo hazard ratio 0·99, 95% CI 0·87—1·14; as-needed vs placebo 1·05, 0·92—1·19; regular vs as-needed 1·05, 0·92—1·20). We recorded no difference between treatment groups for time to recovery (adjusted p=0·79). Adherence to regular tablets (median tablets consumed per participant per day of maximum 6; 4·0 [IQR 1·6—5·7] in the regular group, 3·9 [1·5—5·6] in the as-needed group, and 4·0 [1·5—5·7] in the placebo group), and number of participants reporting adverse events (99 [18·5%] in the regular group, 99 [18·7%] in the as-needed group, and 98 [18·5%] in the placebo group) were similar between groups.
Interpretation
Our findings suggest that regular or as-needed dosing with paracetamol does not affect recovery time compared with placebo in low-back pain, and question the universal endorsement of paracetamol in this patient group.
Funding
The study was funded by the National Health and Medical Research Council of Australia and GlaxoSmithKline Australia. Two coauthors report receiving funding for a postgraduate research scholarship from GlaxoSmithKline, and funding to review teaching materials prepared by GlaxoSmithKline. The other authors, including Dr. Williams, have disclosed no relevant financial relationships.