YAY - We Needed This Study

[ViewsAskew]

http://zedie.wordpress.com/2013/11/11/o ... -syndrome/

Published in The Lancet



The Lancet Neurology, Volume 12, Issue 12, Pages 1141 - 1150, December 2013

This article can be found in the following collections: Neurology (Movement disorders, Neurology-other)

Published Online: 18 October 2013

Copyright © 2013 Elsevier Ltd All rights reserved.

Prolonged release oxycodone—naloxone for treatment of severe restless legs syndrome after failure of previous treatment: a double-blind, randomised, placebo-controlled trial with an open-label extension

Prof Claudia Trenkwalder MD a b Corresponding AuthorEmail Address, Heike Beneš MD c, Ludger Grote MD d, Diego García-Borreguero MD e, Birgit Högl MD f, Michael Hopp MD g, Björn Bosse Dipl Stat g, Alexander Oksche MD g h, Prof Karen Reimer MD g i, Prof Juliane Winkelmann MD j k l, Richard P Allen PhD m, Ralf Kohnen PhD n, for the RELOXYN Study Group†

Background
Opioids are a potential new treatment for severe restless legs syndrome. We investigated the efficacy and safety of a fixed-dose combination of prolonged release oxycodone—naloxone for patients with severe restless legs syndrome inadequately controlled by previous, mainly dopaminergic, treatment.

Methods
This multicentre study consisted of a 12-week randomised, double-blind, placebo-controlled trial and 40-week open-label extension phase done at 55 sites in Austria, Germany, Spain, and Sweden. Patients had symptoms for at least 6 months and an International RLS Study Group severity rating scale sum score of at least 15; patients with severe chronic obstructive pulmonary disease or a history of sleep apnoea syndrome were excluded. Patients were randomly assigned (1:1) to either study drug or matched placebo with a validated interactive response technology system in block sizes of four. Study drug was oxycodone 5·0 mg, naloxone 2·5 mg, twice per day, which was up-titrated according to investigator's opinion to a maximum of oxycodone 40 mg, naloxone 20 mg, twice per day; in the extension, all patients started on oxycodone 5·0 mg, naloxone 2·5 mg, twice per day, which was up-titrated to a maximum of oxycodone 40 mg, naloxone 20 mg, twice per day. The primary outcome was mean change in severity of symptoms according to the International RLS Study Group severity rating scale sum score at 12 weeks. This study is registered with ClinicalTrials.gov (number NCT01112644) and with EudraCT (number 2009-011107-23).

Findings
We screened 495 patients, of whom 306 were randomly assigned and 276 included in the primary analysis (132 to prolonged release oxycodone—naloxone vs 144 to placebo). 197 patients participated in the open-label extension. Mean International RLS Study Group rating scale sum score at randomisation was 31·6 (SD 4·5); mean change after 12 weeks was −16·5 (SD 11·3) in the prolonged release oxycodone—naloxone group and −9·4 (SD 10·9) in the placebo group (mean difference between groups at 12 weeks 8·15, 95% CI 5·46—10·85; p<0·0001). After the extension phase, mean sum score was 9·7 (SD 7·8). Treatment-related adverse events occurred in 109 of 150 (73%) patients in the prolonged release oxycodone—naloxone group and 66 of 154 (43%) in the placebo group during the double-blind phase; during the extension phase, 112 of 197 (57%) had treatment-related adverse events. Five of 306 (2%) patients had serious treatment-related adverse events when taking prolonged release oxycodone—naloxone (vomiting with concurrent duodenal ulcer, constipation, subileus, ileus, acute flank pain).

Interpretation
Prolonged release oxycodone—naloxone was efficacious for short-term treatment of patients with severe restless legs syndrome inadequately controlled with previous treatment and the safety profile was as expected. Our study also provides evidence of open-label long-term efficacy of this treatment. Opioids can be used to treat patients with severe restless legs syndrome who have had no benefit with first-line drugs.

Funding
Mundipharma Research.

[Polar Bear]

Really good news from this study.

[ViewsAskew]

There's never been a solid research study that doctors can turn to related to prescribing opioids. This means more to those of us who use opioids than just about anything.

[cornelia]

This study has been done on OxyContin, very good! On much higher doses (40 mg) than the study done by dr Waltters at the time (5 mg Oxycodon immediate relief if I remember well). They used Naloxone too for constipation but that is optional I should think?
It is remarkable that they said (in another article on this research) that OxyContin should be taken in the morning and at night because of the 'trough' during the day, which is totally true. I wonder if they would OK Tramadol during the day?

Corrie

[karalea]

Thanks so much Corrie for posting this! I have an MD apt today and will bring this info to him. I would think he could prescribe the Oxycodone LA (if there is one) and the Naloxone seperately. I wonder of this would work with any of the other LA Opiods if the Oxycodone is not tolerable. It's also great to see that the side effects are limited.

[cornelia]

Actually Ann posted this study.

OxyContin is the long release of Oxycodone. I'm sure other long working opiates will work as well. Good luck!
Corrie

[ViewsAskew]

Beth and I, for several years, have noted that we need to space out our drugs during the day or else we have a horrible afternoon. Even if I don't need it for the WED in the morning, I need it to prevent that trough they talk about.

I see no reason not to include ANY opioid based on this study. They work relatively the same. But, I'm not a doctor, either!

[QyX]

This study has been done on OxyContin, very good! On much higher doses (40 mg) than the study done by dr Waltters at the time (5 mg Oxycodon immediate relief if I remember well). They used Naloxone too for constipation but that is optional I should think?
It is remarkable that they said (in another article on this research) that OxyContin should be taken in the morning and at night because of the 'trough' during the day, which is totally true. I wonder if they would OK Tramadol during the day?

Corrie

I see no problem with Tramadol but it is a much weaker opioid then Oxycodone.

I have tried Tramadol and Oxycodone in the past. Tramadol was heavily activating me. It also killed my appetite and I was sweating a lot.

Oxycodone was better but it was also activating me. Much less then Tramadol but still strong enough that I always had severe problems falling asleep. I was taking up to 100 mg Oxycodone per day.

I tried a lot of opioids and I ended up taking 15-30 mg of Morphine which doesn't activate me. At the moment I don't need opiods during the day. Only at the evening and night I need Morphine.

I also take Lamotrigine and since yesterday Gabapentin to support the effects of Morphine.

[badnights]

I don't get the naloxone. It is an opioid antagonist. When they are hyping the combo medication, they say the naloxone blocks opioid action in the gut, thereby preventing constipation, but naloxone is used to treat opioid overdose and its consequent dangerous depression of the CNS - so it MUST affect the CNS too. Whenever I read about this combo I am baffled - we are supposed to avoid opioid antagonists like naloxone, even if we are not taking opioids, because opioid antagonists make WED symptoms worse.

I would like to have seen them compare their oxy-nalox combo with just plain old oxy! as well as placebo.

The only reason they are pushing this is because by combining the two meds, they can market it as a new medication. In a way it's better than no research at all being done on opioids for WED, but gee!!! what in the world is the advantage of taking naloxone along with the oxy? If the only advantage is no constipation, that should be handled by diet, not more drugs.

Can someone who has access to the full paper pm me? pretty please?

[QyX]

I just talked today with my Doctor about this study.

For any1 who is interested I have a way of providing you the full text of the study. Just pm me.

I was once in the hospital of Prof. Trenkwalder in Kassel/Germany.

Of course they gave me this drug