A Multicenter, Double-blind, Randomized, Parallel Group Study to Assess the Effect of NCX4016 vs Placebo on Walking Distance in Patients With Peripheral Arterial Occlusive Disease at Leriche-Fontaine Stage II

Peripheral arterial disease (PAD) is almost invariably associated with a generalized atherosclerotic involvement of the arterial tree and endothelial dysfunction. Previous short term studies showed improvement of vascular reactivity and walking capacity in PAD patients by measures aimed at restoring Nitric Oxide (NO) production. NO is also known to prevent the progression of atherosclerosis. We wished to assess whether the prolonged administration of a NO-donating agent (NCX 4016) improves the functional capacity of PAD patients and affects the progression of atherosclerosis as assessed by carotid intima-media thickness (IMT).
Four hundred forty two patients with stable intermittent claudication were enrolled in a prospective, double blind, placebo-controlled study and randomized to either NCX 4016 800mg bid or its placebo for 6 months. The primary study outcome was the absolute claudication distance (ACD) on a constant treadmill test (10% incline, 3km/hr); main secondary end-point was the change of the mean far-wall right common carotid artery IMT.

Start Date01 Sep 2003

Sponsor / Collaborator

Nicox Research Institute Srl

NCT00157508 / TerminatedPhase 2IIT

A Pilot, Randomised, Double-blind, Cross-over Study to Assess the Renal and Systemic Effects of NCX4016 in Patients With Type 2 Diabetes and Early Nephropathy

Aspirin is commonly used for treatment of painful and inflammatory diseases and in the prevention of the cardiovascular disease. A major drawback of aspirin treatment is the well recognized gastrointestinal toxicity. Recent research indicate that coupling a nitric oxide (NO)derivate to the aspirin moiety retains its therapeutic effects while avoiding its undesirable gastrointestinal side effects. NO has cytoprotective effects, such as blood flow modulation, mucus release and repair of mucosal injury. NCX4016, a NO-releasing derivative of acetylsalicilic acid, has been shown to retain the analgesic, anti-inflammatory and antithrombotic activity of aspirin, but with less gastrointestinal toxicity. In addition, preliminary data suggested that NCX4016 may restore insulin sensitivity in eNOS deficient mice.
This study was aimed to evaluate the activity of NCX4016, compared to aspirin, on albuminuria, insulin sensitivity and cardiac and renal hemodynamic in patients with type 2 diabetes mellitus. The patients after one month of placebo treatment, entered two 1-month treatments periods, with equivalent doses (800 mg of NCX4016, 325 mg of aspirin) of NCX4016 or aspirin.

Start Date01 Mar 2003

Sponsor / Collaborator-

100 Clinical Results associated with Nitroaspirin

100 Translational Medicine associated with Nitroaspirin

100 Patents (Medical) associated with Nitroaspirin

215

Literatures (Medical) associated with Nitroaspirin

14 Aug 2024·European heart journal. Cardiovascular pharmacotherapy

Aspirin-free strategy for percutaneous coronary intervention in acute coronary syndrome based on the subtypes of acute coronary syndrome and high bleeding risk: the STOPDAPT-3 trial

Article

Author: Ikari, Yuji ; Shiode, Nobuo ; Kozuma, Ken ; Yamamoto, Ko ; Abe, Koji ; Kaitani, Kazuaki ; Ogata, Nobuhiko ; Akashi, Yoshihiro J ; Hayashi, Fujio ; Kurita, Tairo ; Nishida, Yasunori ; Hibi, Kiyoshi ; Matsuoka, Shunzo ; Natsuaki, Masahiro ; Kimura, Takeshi ; Kawahatsu, Kando ; Inoko, Moriaki ; Kumagai, Koji ; Ishihara, Shozo ; Morino, Yoshihiro ; Nakano, Yukiko ; Nishikawa, Ryusuke ; Morishima, Itsuro ; Tanaka, Hiroyuki ; Fujita, Takanari ; Hata, Yoshiki ; Suzuki, Hiroshi ; Wakabayashi, Kohei ; Okayama, Hideki ; Morimoto, Takeshi ; Yamaguchi, Junichi ; Yamada, Minoru ; Watanabe, Hirotoshi ; Tanabe, Kengo ; Nozaki, Yoichi ; Wakatsuki, Tetsuzo ; Sakamoto, Hiroki ; Noda, Toshiyuki ; Onishi, Yuko ; Takenaka, Hiroyuki ; Nakazawa, Gaku ; Ando, Kenji ; Nakano, Masatsugu ; Nanasato, Mamoru ; Kawai, Kazuya ; Kaneko, Takeo ; Yokomatsu, Takafumi ; Sugimoto, Atsuhiko ; Makiguchi, Noriko ; Takaya, Tomofumi ; Kato, Ryuichi ; Kobayashi, Yoshio ; Kinoshita, Makoto ; Isawa, Tsuyoshi ; Obayashi, Yuki ; Nishikura, Tenjin ; Higuchi, Motoaki ; Miura, Shin-Ichiro ; Nishida, Koji ; Yoshida, Ruka ; Doi, Masayuki ; Tamura, Toshihiro ; Abe, Shichiro ; Kirigaya, Hidekuni ; Tsujita, Kenichi ; Ishikawa, Tetsuya ; Wakeyama, Takatoshi ; Doijiri, Tatsuki ; Nakagami, Takuo ; Tanigawa, Takashi ; Tabuchi, Isao ; Ono, Koh ; Akao, Masaharu ; Tomita, Hirofumi ; Serikawa, Takeshi ; Uehara, Hiroki ; Tsubakimoto, Yoshinori ; Kadota, Kazushige ; Suwa, Satoru ; Yumoto, Kazuhiko ; Kusuyama, Takanori ; Tokuyama, Hideo

Abstract:

Background and aims:

High bleeding risk (HBR) and acute coronary syndrome (ACS) subtypes are critical in determining bleeding and cardiovascular event risk after percutaneous coronary intervention (PCI).

Methods and results:

In 4476 ACS patients enrolled in the STOPDAPT-3, where the no-aspirin and dual antiplatelet therapy (DAPT) strategies after PCI were randomly compared, the pre-specified subgroup analyses were conducted based on HBR/non-HBR and ST-segment elevation myocardial infarction (STEMI)/non-ST-segment elevation ACS (NSTE-ACS). The co-primary bleeding endpoint was Bleeding Academic Research Consortium (BARC) type 3 or 5, and the co-primary cardiovascular endpoint was a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischaemic stroke at 1 month. Irrespective of the subgroups, the effect of no-aspirin compared with DAPT was not significant for the bleeding endpoint (HBR [N = 1803]: 7.27 and 7.91%, hazard ratio (HR) 0.91, 95% confidence interval (CI) 0.65–1.28; non-HBR [N = 2673]: 3.40 and 3.65%, HR 0.93, 95% CI 0.62–1.39; Pinteraction = 0.94; STEMI [N = 2553]: 6.58 and 6.56%, HR 1.00, 95% CI 0.74–1.35; NSTE-ACS [N = 1923]: 2.94 and 3.64%, HR 0.80, 95% CI 0.49–1.32; Pinteraction = 0.45), and for the cardiovascular endpoint (HBR: 7.87 and 5.75%, HR 1.39, 95% CI 0.97–1.99; non-HBR: 2.56 and 2.67%, HR 0.96, 95% CI 0.60–1.53; Pinteraction = 0.22; STEMI: 6.07 and 5.46%, HR 1.11, 95% CI 0.81–1.54; NSTE-ACS: 3.03 and 1.71%, HR 1.78, 95% CI 0.97–3.27; Pinteraction = 0.18).

Conclusion:

In patients with ACS undergoing PCI, the no-aspirin strategy compared with the DAPT strategy failed to reduce major bleeding events irrespective of HBR and ACS subtypes. The numerical excess risk of the no-aspirin strategy relative to the DAPT strategy for cardiovascular events was observed in patients with HBR and in patients with NSTE-ACS.

31 Jul 2024·FASEB JOURNAL

RETRACTION: NCX‐4016, a nitric oxide‐releasing aspirin, protects endothelial cells against apoptosis by modulating mitochondrial function

RETRACTION: S. Fiorucci, A. Mencarelli, R. Mannucci, E. Distrutti, A. Morelli, P. del Soldato, S. Moncada, “NCX‐4016, a nitric oxide‐releasing aspirin, protects endothelial cells against apoptosis by modulating mitochondrial function,” The FASEB Journal 16, no. 12 (2002): 1645–1647. https://doi.org/10.1096/fj.02‐0297fje.The above article, published online on 07 August 2002 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor‐in‐Chief, Dr. Loren E. Wold; the Federation of American Societies for Experimental Biology; and Wiley Periodicals LLC. The retraction has been agreed due to concerns raised by a third party regarding the similarity of blots in Figure 7. The authors did not respond to inquiries by either the society or the publisher. In addition, the authors' institution did not respond to our request to begin an investigation. An investigation by the society and the publisher determined that there is overwhelming evidence that images in Figure 7 were manipulated. Because the images in question were imperative to the conclusions presented in the article, all parties agreed the article must be retracted.

01 Jan 2024·Discovery Medicine

Inhibition Effects of Acetylsalicylic Acid with Nitric Oxide (NO-ASA) on Neoplastic Changes in the Exocrine Pancreas Acinar Cells of the Azaserine Injected Rats

Article

Author: Yıldız, Hasan ; Doğan, Serhat

BACKGROUND:

Atypical acinar cell foci (AACF) seen in pancreatic cancer are fatal and have been studied with some causative agents. However, for the first time, the effect of acetylsalicylic acid with nitric oxide (NO-ASA) on AACF was examined in this study. Although NO-ASA has very successful inhibitory effects against some types of cancer, it has not been investigated whether they can exert their inhibition effects on AACFs.

METHODS:

For experimental purposes, 21 14-day-old male Wistar albino rats were used. Azaserine (30 mg/kg) was dissolved in 0.9% NaCl solution and injected intraperitoneally (i.p.) into 14 rats, except for the Control group (Cont) rats, for three weeks. Rats that were injected with azaserine once a week for three weeks and those that did not receive treatment were divided into experimental groups. 15 days after the end of the azaserine injection protocol, NO-ASA was applied to azaserine with NO-ASA (Az+NO-ASA) group rats three consecutive times with an interval of 15 days by gavage. At the end of the 5-month period, pancreatic tissue was dissected and weighed. Pancreas preparations prepared from histological sections were examined for AACF burden and analyzed via a video image analyzer. One-way analysis of variance (ANOVA) non-parametric statistical analyses were performed to test whether there was a difference between the averages of the experimental and Control groups.

RESULTS:

AACF burden in both groups injected with azaserine was found to be statistically significant in all categories compared to that of the Control group (p < 0.05). The average Calculated Estimated average AACF volume (mm³) values, the Calculated estimated average AACF diameter (μm), the Estimated average number of AACF per unit volume, AACF rate as a % of Calculated Organ Volume were higher in the AzCont group rats than in the Az+NO-ASA group, when compared, and there was an important level statistical difference between the groups (p < 0.05). It was determined that for all parameters AACFs load in Az+NO-ASA group rats were significantly reduced compared to that of AzCont group rats (p < 0.05).

CONCLUSIONS:

We observed that, as a result of the NO-ASA application, the experimental AACF focus ratio created by azaserine injection was significantly inhibited. The inhibitory effect of AACFs in Az+NO-ASA group rats may have resulted from the significant and independent chemopreventive and/or chemotherapeutic activity of NO-ASA against exocrine pancreatic AACF foci.

100 Deals associated with Nitroaspirin

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R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Intermittent Claudication	Phase 2	IT	Nicox Research Institute Srl	01 Sep 2003
Peripheral arterial occlusive disease	Phase 2	IT	Nicox Research Institute Srl	01 Sep 2003
Diabetes Mellitus, Type 2	Phase 2	IT	Nicox SA	-
Diabetes Mellitus, Type 2	Phase 2	CH	Nicox SA	-
Pain	Phase 2	US	Nicox SA	-

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