Non-inferiority In Terms Research Articles

Antipyretic and Analgesic Effects of Zaltoprofen for the Treatment of Acute Upper Respiratory Tract Infection: Verification of a Noninferiority Hypothesis Using Loxoprofen Sodium

A multicenter, placebo-controlled, double-dummy, randomized, parallel-group, double-blind study was conducted to verify the hypothesis of noninferiority for single-dose administration of zaltoprofen 160 mg, a nonsteroidal anti-inflammatory drug, compared with loxoprofen sodium 60 mg (loxoprofen), in terms of antipyretic and analgesic effects in patients with acute upper respiratory tract infection. The eligible 330 patients were assigned to one of 3 groups: zaltoprofen 160 mg, loxoprofen 60 mg and placebo. The analysis set consisted of 322 patients. Antipyretic effects were assessed by measuring body temperature, and analgesic effects were evaluated using a visual analog scale (VAS) for 4 h under the control of study staff. A detection kit for influenza virus A and B antigens was used to determine the presence of influenza virus infection. Compared with immediately before administration and with the placebo group, significant decreases in body temperature and summary VAS pain scores were noted in both the zaltoprofen and loxoprofen groups at 4 h after drug administration. Based on the degree of decrease in body temperature and the summary VAS pain scores up to 4 h after administration, noninferiority in terms of antipyretic and analgesic effects of zaltoprofen compared with those of loxoprofen was confirmed after single administration. Similar antipyretic and analgesic effects were also confirmed in influenza virus antigen-positive patients (73 patients). No clinical concerns were identified regarding safety. Zaltoprofen and loxoprofen are confirmed to be safe and useful for patients with acute upper respiratory tract infection, including those with influenza infection.

Using Floating Atrial Electrodes to Combat the Rising Tide of Inappropriate Defibrillator Therapies

Despite various implantable defibrillator algorithms and strategies used to improve discrimination between potentially life-threatening ventricular arrhythmias (ventricular tachycardia/ventricular fibrillation [VT/VF]) and more benign supraventricular tachycardias (SVTs), this remains a problem. In addition to significant discomfort and impairment of quality of life, there is some suggestion that shocks may increase mortality.1 Recording atrial intracardiac electrograms during arrhythmic episodes would be expected to improve our ability to discriminate tachycardias and thus reduce the number of inappropriate shocks. It may also lead to the diagnosis of otherwise unsuspected atrial arrhyhmias that may require specific therapy, such as anticoagulation therapy for patients with atrial flutter or atrial fibrillation (AF). Article see p 56 The evidence available so far, however, does not clearly demonstrate that atrial electrograms reduce inappropriate shocks.2–7 Although some studies performed in patients with a dual-chamber device have shown a reduction in inappropriate detection, inappropriate shocks also were avoided in the single-chamber detection arm by using anti tachycardia pacing.2 In addition, placement of an atrial lead is associated with a risk of lead dislodgement (≈4.5%) and increased procedural and fluoroscopy times compared to a single-chamber defibrillator. Thus, there currently is no strong evidence to support the addition of an atrial lead for the sole purpose of SVT discrimination and reducing implantable cardioverter-defibrillator (ICD) shocks.8 Using a single-pass VDD defibrillator lead holds the promise of offering atrial electrograms without the additional risks and procedural time related to implantation of a separate atrial lead. Similar lead designs with integrated atrial electrodes have been used in VDD pacemakers.9 In a study published by Sticherling et al in this issue of Circulation: Arrythmia and Electrophysiology , the ADRIA (Study to Verify Proper Detection of Supraventricular Tachyarrhythmia With Single-Lead Dual-Chamber Implantable Cardioverter-Defibrillators) study, the authors investigated the use …

Efficacy and safety of oral lactoferrin supplementation associated with rHuEPOβ for the treatment of anemia in advanced cancer patients submitted to chemotherapy.

e19515 Background: Advanced stage cancer patients often suffer from anemia which closely resembles the anemia of chronic inflammatory diseases characterized by peculiar changes in iron homeostasis and absorption. Intravenous (IV) iron improves the efficacy of recombinant human erythropoietin (rHuEPO) in anemic cancer patients undergoing chemotherapy. Methods: We report the results of a phase III randomized trial aimed to test the non-inferiority in terms of efficacy and safety of a treatment with oral lactoferrin versus IV iron, both in association to rHuEPO, for the treatment of anemia in a population of 85 advanced cancer patients submitted to chemotherapy. All patients received subcutaneously rHuEPO β 30000 IU once weekly for 12 weeks and were randomly assigned to ferric gluconate 125 mg IV weekly or oral lactoferrin 200 mg/day. Results: Both arms showed a significant hemoglobin increase. No difference in mean hemoglobin increase as well as hematopoietic response, time to hematopoietic response, mean changes of serum iron, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were observed between arms. Vice versa, ferritin decreased in lactoferrin arm while it increased in IV iron arm. Conclusions: These results showed a similar efficacy of oral lactoferrin in comparison to IV iron, in association of rHuEPO, for the treatment of anemia in advanced cancer patients submitted to chemotherapy. No significant financial relationships to disclose.

Two-Year Clinical, Angiographic, and Intravascular Ultrasound Follow-Up of the XIENCE V Everolimus-Eluting Stent in the Treatment of Patients With De Novo Native Coronary Artery Lesions: The SPIRIT II Trial

Two-Year Clinical, Angiographic, and Intravascular Ultrasound Follow-Up of the XIENCE V Everolimus-Eluting Stent in the Treatment of Patients With De Novo Native Coronary Artery Lesions: The SPIRIT II Trial

Two-Year Clinical, Angiographic, and Intravascular Ultrasound Follow-Up of the XIENCE V Everolimus-Eluting Stent in the Treatment of Patients With De Novo Native Coronary Artery Lesions

This article reports the 2-year clinical, angiographic, and intravascular ultrasound outcomes of the everolimus-eluting stent (EES) compared with the paclitaxel-eluting stent (PES) in the randomized SPIRIT II trial. This was a prospective, single-blind clinical trial in which a total of 300 patients with de novo native coronary artery lesions were randomized to either EES or PES in a 3:1 fashion. Clinical follow-up was planned at 2 years in all patients. A subset of 152 patients underwent serial angiographic and intravascular ultrasound analyses at 6 months and 2 years. After 2 years, target lesion failure (cardiac death, myocardial infarction, and ischemia-driven target lesion revascularization) rates were 6.6% and 11% in EES and PES, respectively (P=0.31). At 6 months, a significant reduction in angiographic in-stent late loss and percentage volume obstruction measured by intravascular ultrasound was observed in the EES group. However, at 2-year follow-up, a late increased intimal hyperplasia growth after implantation of an EES was observed. There were no significant differences between EES and PES for in-stent late loss (EES, 0.33+/-0.37 mm versus PES, 0.34+/-0.34 mm; P=0.84) and percentage volume obstruction (EES, 5.18+/-6.22% versus PES, 5.80+/-6.31%; P=0.65) at 2 years. The incidence of stent thrombosis was low and comparable in both groups (EES, 0.9%; PES, 1.4%). Although the previously reported angiographic and clinical superiority of the EES has vanished over time, this report confirms and extends the previously demonstrated noninferiority in terms of in-stent late loss of the EES when compared with the PES up to 2-year follow-up. There were no significant differences between EES and PES in clinical, angiographic and intravascular ultrasound outcomes at 2 years.

Methods for Equivalence and Noninferiority Testing

Classical hypothesis testing focuses on testing whether treatments have differential effects on outcome. However, sometimes clinicians may be more interested in determining whether treatments are equivalent or whether one has noninferior outcomes. We review the hypotheses for these noninferiority and equivalence research questions, consider power and sample size issues, and discuss how to perform such a test for both binary and survival outcomes. The methods are illustrated on 2 recent studies in hematopoietic cell transplantation.

Efficacy of antiglaucoma fixed combination therapy versus unfixed components in reducing intraocular pressure: a systematic review

Aim:To evaluate the efficacy of the fixed combination ocular hypotensive therapies compared with their non-fixed components used concomitantly for lowering intraocular pressure (IOP) in glaucoma and ocular hypertension.Methods:A systematic review...

Efficacy and safety findings from a randomized phase III study of capecitabine (X) + oxaliplatin (O) (XELOX) vs. infusional 5- FU/LV + O (FOLFOX-6) for metastatic colorectal cancer (MCRC)

4029 Background: X has comparable efficacy, safety and convenience benefits over 5-FU/LV (Mayo clinic) in adjuvant colon cancer and first-line MCRC. A recent phase III trial in first line MCRC showed that XELOX is well tolerated and non inferior to FOLFOX-4 for progression-free survival (PFS) [Cassidy ESMO 2006]. Methods: We initiated a phase III trial to demonstrate non inferiority in terms of best response rates (RR, RECIST) of XELOX versus FOLFOX-6 as first-line therapy in patients (pts) with MCRC. Between 16 May 03 and 31 Aug 04, 306 patients (intention to treat), were randomized to receive either XELOX (n=156: × 1,000mg/m2 bid d1–14, O 130mg/m2 d1, q3w) or FOLFOX-6 (n=150: O 100mg/m2 d1 LV 400mg/m2 2h infusion then 5-FU 400mg/m2 i.v. bolus then 2,400–3,000mg/m2 46h infusion, q2w) for 6 months. Efficacy results are presented in the per protocol population (PP) (n=284:144 pts XELOX; 140 pts FOLFOX-6). Results: Baseline characteristics were well balanced. Pts received a median of 8 and 11 cycles of XELOX (range 0–8) and FOLFOX-6 (range 0–12), respectively. Dose intensity (median) for oxaliplatin was 99.6% and 95.4% with XELOX and FOLFOX-6, respectively. Best RR (independent review, PP) was 42% and 46% with XELOX and FOLFOX-6, respectively. Difference between groups for RR was 4.7%; upper limit of 95% unilateral CI (14.4%) was below non-inferiority margin of 15%. RR by investigators (PP) was 46% for each arm. With a median follow up of 16.5 months (range 0.4–38.3), median PFS and overall survival (PP) were 9.3/19.9 vs. 9.7/18.4 months with XELOX and FOLFOX-6, respectively. In the safety population (n=304), XELOX pts had more grade 3/4 hand-foot syndrome (3 vs. 0%, p=0.21), thrombocytopenia (12 vs. 5% p=0.052), and diarrhea (12% vs. 7% p=0.1), but less grade 3/4 febrile neutropenia (0 vs. 6% p=0.001), neuropathy (8 vs. 19% p=0.003), than those on FOLFOX-6. Treatment discontinuation for toxicity was 19% and 23% in XELOX and FOLFOX-6 arms, respectively. Conclusions: The primary endpoint has been met: XELOX is non inferior to FOLFOX-6, with a good safety profile in first-line MCRC. No significant financial relationships to disclose.