Clinical evaluation of the peak inspiratory flow generated by asthmatic children through the Novolizer.

STUDY OBJECTIVE: To assess whether asthmatic children may generate sufficient peak inspiratory flow through the Novolizer, a novel multiple dose dry powder inhaler with acoustic and optical feedback mechanisms for correct inhalation. PATIENTS AND METHODS: 137 children (median age 7 years, range 4-2) with mild to moderate persistent asthma (FEV1 < 90% predicted or pre-treated with low-dose steroids) participated in this open, multi-centre study. After assessment of FEV1 and peak inspiratory flow (without inhalator device, PIF), the children were instructed to inhale with the Novolizer (PIF through inhaler, PIF-N). All assessments were done in triplicate and the mean out of three attempts analysed. RESULTS: Mean PIF was 128 +/- 61 l/min and mean PIF-N was 69 +/- 18 l/min. This is distinctly above the rate necessary to overcome the Novolizer's trigger threshold. PIF performance through the Novolizer was linear in the age interval of 4-8 years, no further increase was observed beyond 8 years. CONCLUSIONS: The medium to low intrinsic resistance of the Novolizer permits a relatively high PIF through this device. Together with the feedback mechanisms, this makes the Novolizer particularly valuable for inhalation therapy in asthmatic children with drugs such as salbutamol, formoterol, or budesonide.

Clinical equivalence trial on budesonide delivered either by the Novolizer multidose dry powder inhaler or the Turbuhaler in asthmatic patients.

BACKGROUND AND OBJECTIVES: To investigate the therapeutic equivalence of the two formulations of the glucocorticosteroid budesonide delivered either by the budesonide Novolizer, i.e. a multidose dry powder inhaler, or by the Pulmicort Turbuhaler in asthmatic patients in terms of efficacy, safety and tolerability during a 12-week treatment. METHODS: A total of 315 patients were randomised in this open, multicentre study. Inclusion criteria comprised previously diagnosed bronchial asthma of mild to moderate persistent intensity (ranging from 60% to a maximum of 90% predicted FEV(1)), need for anti-inflammatory therapy, inhalation of beta(2)-sympathomimetics on an as needed to regular basis, reversibility of airway obstruction of >12% after inhalation of 2 actuations of 100 microg salbutamol. Primary variable was FEV(1), secondary were other pulmonary function test variables, PC(20)FEV(1) for histamine challenge, morning and evening PEFR, salbutamol usage, asthma symptoms, reactions after inhalation, standard safety variables. RESULTS: The comparison of the FEV(1) at study endpoint indicated that the Novolizer was at least as efficacious as the Turbuhaler (p < 0.001). All other variables of the pulmonary function tests as well as the asthma symptoms, nocturnal awakenings, PEFR measurements, or salbutamol usage indicated no relevant difference. Only 1 patient (Turbuhaler discontinued prematurely due to lack of efficacy. None of the other safety variables (adverse events, laboratory variables, vital signs, etc.) indicated any difference between the groups. CONCLUSIONS: The budesonide Novolizer is therapeutically equivalent to the Pulmicort Turbuhaler for the long-term treatment of patients with mild to moderate persistent asthma.

[Therapy of heart failure with spirapril--the open phase of the CASSIS study. Analysis of the 2nd year extension of the CASSIS study]. / Lécba srdecního selhání spiraprilem--otevrená fáze studie CASSIS. Analýza 2. roku extenze studie CASSIS.

The CASSIS study was a double-blind multicentric controlled Czech and Slovak study focused on treatment of chronic heart failure with the ACE inhibitor spirapril; it was conducted for 12 weeks. The present work analyzes the second year of the extended open part of the study when all patients (n = 168) were treated with 3 mg or 6 mg spirapril. A small proportion of the patients was treated with 12 mg spirapril. The objective of the study was to test the long-term effectiveness and tolerance of spirapril. The general mortality was analyzed throughout the whole two-year period. The results revealed an unchanging total mortality, analyzed after three-month intervals, during the whole two-year period. Also the functional improvement of the patients according to NYHA which occurred after the first three months of treatment was preserved during the second year. Spirapril proved to be a well tolerated ACE-inhibitor. The authors did not observe angioneurotic oedema in any of the patients. Hypotension and cough were recorded in 0.6% of the patients. The incidence of undesirable laboratory effects was also low and the majority was due to the basic disease. Creatinine did not rise significantly and a rise of urea was observed only in a small number of patients. Liver functions and haemogram did not change during treatment. The results of the second year of erxtension indicate that spirapril is a very effective and safe ACE-inhibitor which will extend in a significant way therapeutic means in patients with chronic heart failure.

[A Czech and Slovak interventional study of spirapril (the CASSIS study). A randomized, double-blind, multicenter, placebo-controlled study in chronic heart failure]. / Ceská a slovenská intervencní studie se spiraprilem (studie CASSIS). Randomizovaná, dvojiteslepá, multicentrická studie, kontrolovaná aktivne i placebem chronického srdecního selhání. Za resitele studie CASSIS.

Spirapril, an ACE-inhibitor without the SH group was tested in a randomized double-blind multicentric study in patients with chronic symptomatic heart failure (NYHA II-IV). After a 1-4-week initial stage with placebo the patients were randomized into five groups: the first was given placebo, the second one spirapril 1.5 mg, the third one spirapril 3 mg, the fourth one spirapril 6 mg and the fifth one 5 and later 10 mg for a period of 12 weeks. The number of patients in different groups was in the following order: 48, 48, 53, 51 and 48. The condition for admission into the study was chronic heart failure not responding adequately to treatment with digoxin and diuretics, IHD or dilatation cardiomyopathy with the left ventricular ejection fraction (% tolerating a basic ergometric load for two minutes. The primary criterium was an increment during the period of the load, secondary criteria comprised objective and subjective cardiac symptoms, changes in the left ventricular ejection fraction, cardiothoracic index/heart size and quality of life. The load tolerance increased in all groups, however, no significant differences between groups were found. The authors also found regression of signs of pulmonary congestion during active spirapril treatment and diminution of the cardiac shadow. Moreover the authors proved a significant reduction of the mortality in the actively treated patients as compared with those receiving placebo, a lower frequency of hospital admissions and reduction of serious undesirable cardiovascular symptoms during active treatment. In patients with medium severe and severe cardiac failure with IHD, combination with short acting calcium channel blockers had an unfavourable effect on the load tolerance and clinical parameters. Sprirapril, combined with diuretics and digoxin is a suitable drug also in chronic cardiac failure. Questionable remains the importance of loading tests when verifying the effectiveness of ACE-inhibitors. Treatment with short-time acting calcium antagonists cannot be recommended in symptomatic chronic cardiac failure.

Czech and Slovak spirapril intervention study (CASSIS). A randomized, placebo and active-controlled, double-blind multicentre trial in patients with congestive heart failure.

A randomized, double-blind, placebo- and active-controlled multicentre study with spirapril, a new angiotensin-converting enzyme inhibitor (ACEI), has been conducted in patients with chronic congestive heart failure (CHF) of NYHA classes II-IV. After a placebo run-in period of 1-4 weeks, patients were randomly assigned to one of five treatment groups: placebo (n = 48), spirapril 1.5 mg (n = 48), spirapril 3 mg (n = 53), spirapril 6 mg (n = 51) or enalapril 5/10 mg (n = 48). The primary objective was to assess changes in exercise tolerance, and the secondary objective was an assessment of cardiovascular signs and symptoms, quality of life, ejection fraction and chest X-ray findings. Exercise tolerance increased in all groups; however, no statistically significant differences were found between any of the groups. There was a statistically significant reduction of mortality in the pooled spirapril groups compared with placebo, and a trend for reduction of serious cardiovascular adverse events as well as duration of hospitalization. These effects and improvements in lung congestion appeared to be dose dependent. In patients with moderate to severe heart failure, the combination with first-generation calcium channel blockers had an unfavourable effect on exercise capacity and clinical parameters. Spirapril might be an effective alternative to enalapril in the treatment of patients with CHF. The role of the exercise tolerance test in establishing efficacy of ACEIs in CHF and the widespread use of nifedipine in CHF is questioned.