A multi-centre, blinded, randomised, placebo-controlled, laboratory-based study of MQX-503, a novel topical gel formulation of nitroglycerine, in patients with Raynaud phenomenon

Hummers, Laura K.; Dugowson, Carin E.; Dechow, Frederick J.; Wise, Robert A.; Gregory, Jeffrey; Michalek, Joel E.; Yenokyan, Gayane; McGready, John; Wigley, Fredrick M.

doi:10.1136/annrheumdis-2012-201536

Cited by 38 publications

(15 citation statements)

References 15 publications

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“…Topical GTN has previously been investigated as a ‘local’ treatment for RP (including SSc-related RP) and is currently being revisited (Hummers et al, 2013). In a small crossover study of topical GTN for secondary RP (mainly SSc), Franks (1982) observed there was a marked improvement in DUs with GTN, but not with placebo.…”

Section: Discussionmentioning

confidence: 99%

Reduced perfusion in systemic sclerosis digital ulcers (both fingertip and extensor) can be increased by topical application of glyceryl trinitrate

Hughes

Moore

Manning

et al. 2017

Microvascular Research

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ObjectivesIn patients with systemic sclerosis (SSc), fingertip digital ulcers (DUs) are believed to be ischaemic, and extensor surface DUs a result of mechanical factors/microtrauma. Our aim was to assess blood flow response to topical glyceryl trinitrate (GTN) compared to placebo in SSc DUs, looking for differences in pathophysiology between fingertip and extensor lesions.MethodThis was a double-blind, randomised, crossover, placebo-controlled study. Sixteen (6 fingertip, 10 extensor) DUs were each studied twice (one day apart): once with GTN and once with placebo ointment. Perfusion at the DU centre (‘DUCore’) and periphery (‘DUPeriphery’), as measured by laser Doppler imaging was performed before and immediately after ointment application, then every 10 min, up to 90 min post-application. We calculated the area under the response curve (AUC) and the ratio of peak perfusion to baseline, then compared these between GTN and placebo.ResultsPerfusion was lower in the DUCore compared to the DUPeriphery (ratio of 0.52). The microvessels of the DUCore were responsive to GTN, with an increase in perfusion, with a similar effect in both fingertip and extensor DUs. The AUC and peak/baseline perfusion difference in means (ratio, 95% confidence interval) between GTN and placebo at the DUCore were 1.2 (1.0–1.6) and 1.2 (1.0–1.5) respectively, and at the DUPeriphery were 1.1 (0.8–1.6) and 1.0 (0.9–1.2) respectively.ConclusionDUs (both fingertip and extensor) were responsive to topical GTN, with an increase in perfusion to the ischaemic DU centre. If both fingertip and extensor DUs have a (potentially reversible) ischaemic aetiology, this has important treatment implications.

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Section: Discussionmentioning

confidence: 99%

Reduced perfusion in systemic sclerosis digital ulcers (both fingertip and extensor) can be increased by topical application of glyceryl trinitrate

Hughes

Moore

Manning

et al. 2017

Microvascular Research

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“…Adverse side eff ects, such as headache, fl ushing, light-headedness, decreased blood pressure, tachycardia and aggravation of gastroesophageal refl ux, can occur. A novel formulation of topical NTG, i.e., MQX-503 gel, with fewer systemic side eff ects, has been assessed in two prospective studies, revealing benefi cial eff ects on the severity and duration of attacks and increased skin blood fl ow measured by laser Doppler techniques [44,47]. In patients with low blood pressure, acute or chronic heart failure, pulmonary hypertension, or concomitant use of a PDE inhibitor, topical nitrates should generally be avoided.…”

Section: Other Oral Vasodilatorsmentioning

confidence: 99%

Raynaud’s phenomenon and digital ischaemia - pharmacologic approach and alternative treatment options

Linnemann

Erbe

2016

Vasa

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Summary:The primary goal of therapy is to reduce the frequency and intensity of Raynaud's attacks and to minimize the related morbidity rather than to cure the underlying condition. Treatment strategies depend on whether Raynaud's phenomenon (RP) is primary or secondary. All patients should be instructed about general measures to maintain body warmth and to avoid triggers of RP attacks. Pharmacologic intervention can be useful for patients with severe and frequent RP episodes that impair the patient's quality of life. Calcium channel blockers are currently the most prescribed and studied medications for this purpose. There has been limited evidence for the effi cacy of alpha-1-adrenergic receptor antagonists, angiotensin receptor blockers, topical nitrates or fl uoxetine to treat RP. The intravenously administered prostacyclin analogue iloprost can reduce the frequency and severity of RP attacks and is considered a second-line therapy in patients with markedly impaired quality of life, critical digital ischaemia and skin ulcers who are at risk for substantial tissue loss and amputation. Phosphodiesterase inhibitors (e.g., sildenafi l) can also improve RP symptoms and ulcer healing whereas endothelin-1 receptor antagonists (e.g., bosentan) are mainly considered treatment options in secondary prevention for patients with digital skin ulcers related to systemic sclerosis. However, their use in clinical practice has been limited by their high cost. Antiplatelet therapy with low-dose aspirin is recommended for all patients who suffer from secondary RP due to ischaemia caused by structural vessel damage. Anticoagulant therapy can be considered during the acute phase of digital ischaemia in patients with suspected vascular occlusive disease attributed to the occurrence of new thromboses. In patients with critical digital ischaemia, consideration should be given to hospitalisation, optimisation of medical treatment in accordance with the underlying disease and evaluation for a secondary, possibly reversible process that is causing or aggravating the clinical symptoms.

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“…V praksi se uporablja bosentan, ki je sintetični zaviralec obeh receptorjev. Pomembno zmanjša število novih razjed pri bolnikih s sekundarnim RF (29), tako da je EULAR priporočila uporabo zdravila, ko so simptomi, kljub zdravljenju s kalcijevimi antagonisti in prostaglandini, še vedno prisotni (34). Predvsem se uporablja za zdravljenje napredovalih oblik sekundarnega RF pri sistemski sklerozi (31).…”

Section: Antagonisti Endotelinskih Receptorjevunclassified

Priporočila za odkrivanje in zdravljenje vazospastičnih motenj (Raynaudovega fenomena)

et al. 2018

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Ključne besede:vazospazem; pobledevanje prstov na mrazu; cianoza Key words:spasm of the arteries; pallor of the digits when cold; cyanosis Citirajte kot/Cite as: Zdrav vestn. 2017; 86:553-61. Priporočila za odkrivanje in zdravljenje vazospastičnih motenj (Raynaudovega fenomena)Recommendations for diagnosis and treatment of vasospastic disorders (Raynaud's phenomenon) IzvlečekV prispevku so predstavljena priporočila za obravnavo bolnikov od suma na vazospastični fenomen (Raynaudov fenomen) do diagnostičnih postopkov in zdravljenja pri primarni obliki bolezni. Priporočila so ovrednotena glede na rezultate raziskav tega področja. AbstractIn the article diagnostic and therapeutic recommendations for the treatment of patients with suspected vasospastic disorders (Raynaud's phenomenon) are presented. All recommendations are evaluated according to evidence and general agreement. UvodPriporočila so napisana tako, da upoštevajo dosedanje izsledke raziskav s tega področja. Pri tem smo upoštevali vrednotenje teh raziskav, ki je predstavljeno v Tabeli 1. OpredelitevRaynaudov fenomen (RF) je pojav, ki ga označuje pretiran prehodni vazokonstrikcijski odgovor digitalnih arterij, kožnih arteriol in arteriovenskih spojev ob stimulaciji simpatičnih živčnih vlaken kot odgovor na mraz, psihični stres ali druge vzroke. Gre za patološki odgovor žilne stene, predvsem endotela, neustrezno živčno kontrolo vazokonstrikcije in vpliv različnih vazoaktivnih humoralnih snovi na žilno steno (1,2).Kaže se kot izrazito ostro omejeno pobledovanje prstov rok ali nog, redkeje drugih aker ali prsnih bradavic. Če izolirano brez jasnega razloga nastopa samopobledovanje, govorimo o primarnem RF, če pa je pretiran vazokonstrikcijski odgovor povezan s kakšnim bolezenskim stanjem, govorimo o sekundarnem RF. EpidemiologijaPrevalenca RF se giblje med 3-5 %, in je precej višja pri mlajših ženskah. Veči-noma (v 90 %) gre za primarni RF (3).

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A multi-centre, blinded, randomised, placebo-controlled, laboratory-based study of MQX-503, a novel topical gel formulation of nitroglycerine, in patients with Raynaud phenomenon

Abstract: Treatment with MQX-503 caused a significant improvement in skin BF compared with placebo. Data from this proof of concept study suggest benefit of MQX-503 in subjects with RP.

Cited by 38 publications

References 15 publications

Reduced perfusion in systemic sclerosis digital ulcers (both fingertip and extensor) can be increased by topical application of glyceryl trinitrate

Reduced perfusion in systemic sclerosis digital ulcers (both fingertip and extensor) can be increased by topical application of glyceryl trinitrate

Raynaud’s phenomenon and digital ischaemia - pharmacologic approach and alternative treatment options

Priporočila za odkrivanje in zdravljenje vazospastičnih motenj (Raynaudovega fenomena)

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