A study of recombinant human erythropoietin in the treatment of anaemia of chronic renal failure in children on haemodialysis.

This was an open-label multicentre study of recombinant human erythropoietin (r-HuEPO) in 116 children aged 6 months to 20 years with anaemia of chronic renal failure undergoing haemodialysis. Haemoglobin concentration at entry ranged from 3.4 to 9.5 g/dl. r-HuEPO was given intravenously two or three times per week, the starting dose being 75 U/kg per week. This was subsequently titrated in steps of 75 U/kg per week with the goal of increasing haemoglobin concentration at the rate of 1 g/dl per 4 weeks into the range 9.6-11.2 g/dl (6-7 mmol/l), with treatment then continued for up to 1 year with the aim of maintaining the haemoglobin concentration within the target range. Of the 115 children in whom efficacy could be evaluated, 93 (81%) achieved the target haemoglobin and a further 6 had a rise in haemoglobin concentration of at least 2 g/dl. At 52 weeks, the median maintenance dose for children < 30 kg was 225 U/kg per week, compared with 107 U/kg per week for children > or = 30 kg. Analysis suggested that 150 U/kg per week would have been a more appropriate starting dose. The mean transfusion requirement fell from 8.9 to 0.7 units/patient per year. Of the 22 patients who failed to reach the target, 15 went on to transplantation and left the study prematurely. Sub-group analysis showed that similar doses lead to similar rates of rise in haemoglobin regardless of the severity of the original anaemia. Assessment of quality of life suggested that this may have improved with r-HuEPO.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of transfusion-dependent anaemia of chronic renal failure with recombinant human erythropoietin. A European multicentre study in 142 patients to define dose regimen and safety profile.

This multicentre study in 142 transfusion-dependent patients with chronic renal failure maintained by haemodialysis was performed to establish the appropriate dose regimen of rHuEpo and define its long-term safety profile. Only one of 132 patients eligible for efficacy analysis did not achieve the haemoglobin target of greater than or equal to 10 g/dl; this particular patient had folate deficiency and overt hyperparathyroidism. Regular blood transfusions were no longer necessary in any patients, however five patients needed blood transfusions only once, not due to rHuEpo failure: two for iron deficiency and three for intercurrent disease. In parallel with the haemoglobin increase a statistically significant improvement in quality of life scores was observed. The weekly dose required to maintain median haemoglobin between 10 and 10.5 g/dl for 1 year (n = 79) was 200-225 U/kg, applied as two or three i.v. injections. Mean serum ferritin decreased from 1900 to 1300 ng/ml and transferrin saturation from 60% to 30%; this feature was associated with statistically significant decrease of pre-study elevated liver enzymes. The treatment had no untoward effect on the outcome of renal transplantation (n = 24). Of the 56 patients who experienced hypertensive episodes during rHuEpo therapy, 47 had a history of hypertension and nine had not. The patient incidence during the first 3 months was 28.9% and fell markedly to 4% after 1 year. Only two hypertensive episodes could not be controlled and the patients dropped out. Seizures occurred in 11 patients, most of them during early treatment; annualised incidence during the first 3 months was 7.78 per year vs 2.07 per year for seizures beyond 3 months treatment. Clinical presentation, patients' history, haemoglobin pattern, BP recordings, brain scan, and EEG indicated that the pathophysiology is multifactorial, with emphasis on rate of haemoglobin increase. Therefore a smooth haemoglobin increase rate, induced by a conservative starting dose regimen (50 U/kg thrice weekly) is recommended, to allow the circulation to adapt to changes in haematocrit/viscosity and O2 delivery. The majority of the observed adverse reactions were related to rHuEpo's therapeutic effect, i.e. increase the haematocrit. The side-effects are therefore largely predictable and can be successfully managed.

Rioprostil, a new prostaglandin E1 analogue does not affect glucose homeostasis in healthy volunteers.

Rioprostil is a synthetic prostaglandin E1 analogue currently under study for peptic ulcer healing. Rioprostil, like prostaglandin E, caused an impairment of glucose tolerance in animal studies. We have studied the effects of single therapeutic doses of rioprostil (300 micrograms and 600 micrograms) on glucose homeostasis after oral glucose tolerance tests in 12 healthy volunteers. Plasma glucose, insulin, and C-peptide concentrations were not significantly different after rioprostil and placebo. These results indicate that a clinically significant interference of rioprostil with glucose tolerance is unlikely.

Rioprostil, a new prostaglandin E1 analogue, in the once-daily treatment for the prevention of duodenal ulcer recurrence: a comparison with ranitidine.

The efficacy of Rioprostil (a new prostaglandin E1 analogue) is compared with that of ranitidine in the recurrence prevention of duodenal ulcer(s). Duration of treatment is 6 months. Ninety-seven patients received rioprostil, 600 micrograms once-daily orally, and 110 patients received ranitidine, 150 mg once-daily orally. On rioprostil, 14.9% of patients showed a relapse after 6 months compared to 10.1% on ranitidine. Diarrhoea occurred in 7 patients on rioprostil and 3 patients on ranitidine. Rioprostil given 600 micrograms daily in the evening is a highly effective treatment for the prevention of duodenal ulcer relapse, the efficacy not being significantly different from ranitidine 150 mg.

Rioprostil, a new prostaglandin E1 analogue, in the once-daily treatment of acute duodenal ulcer: a comparison with ranitidine.

The efficacy of Rioprostil (a new prostaglandin E1 analogue) is compared with ranitidine in the once-a-day treatment in the evening for 4 or 6 weeks of active uncomplicated duodenal ulcer disease. A total of 255 patients are entered in this study; of these 243 have been statistically evaluated. One hundred and twenty (120) patients receive rioprostil 600 micrograms/daily, and 123 patients receive ranitidine 300 mg/daily. After 4 weeks 63.3% of the patients on rioprostil are endoscopically healed, as compared with 69.1% on ranitidine. After 6 weeks the cumulative cure rates are 87.3% and 89.9%, respectively, the difference not being statistically significant. Pain relief is similar for both drugs. Diarrhoea with rioprostil occurs in about 2% of the treatment days and is generally self-limiting.

Efficacy and safety of rioprostil, 300 micrograms b.d., in the treatment of gastric ulcer: a comparison vs. ranitidine, 150 mg b.d., in a randomized multicentre study.

The aim of this study is a double-blind evaluation of the efficacy and safety of rioprostil, 300 micrograms, compared with ranitidine, 150 mg, when given twice a day for 4 or 8 weeks in patients with active, uncomplicated gastric ulcer disease. A total of 194 patients are entered into the study, of which 182 are statistically evaluated for efficacy. Eighty-seven receive rioprostil and 95 receive ranitidine. All patients receive two oral doses of study medication daily. After 4 weeks' treatment, 47.1% of the patients receiving rioprostil are endoscopically healed compared with 53.7% of those receiving ranitidine. After 8 weeks' treatment, the cumulative cure rates are 76.2% and 80.9% respectively. Side effects occur in 26% of the patients receiving rioprostil and in 15% of the patients receiving ranitidine. Gastrointestinal side effects are most common. Changes in stool consistency (i.e. soft stools or mild diarrhoea) are the most reported symptoms in patients receiving rioprostil. These effects are generally self-limiting. Three patients on rioprostil and one patient on ranitidine discontinue treatment due to side effects. No clinically significant changes in biochemical variables occur in either group throughout the treatment period. Rioprostil, 300 micrograms b.d., is a safe and effective treatment for gastric ulcer disease. Healing rates and alleviation of pain are comparable for both treatment groups. The change in stool consistency with rioprostil is of only minor clinical importance, that is, it occurs on about 2% of treatment days.

Efficacy and safety of rioprostil, 300 micrograms b.d., in the treatment of duodenal ulcer: a double-blind, controlled multicentre clinical study vs. ranitidine.

This study is undertaken to evaluate the efficacy and safety of rioprostil, 300 micrograms, compared with ranitidine, 150 mg, when given twice daily for 4-6 weeks to patients with active, uncomplicated duodenal ulcer. The effects of each drug on ulcer healing are evaluated by endoscopy. Of a total of 355 patients who have entered this study, 319 are statistically evaluated for efficacy; 162 receive rioprostil and 157 receive ranitidine. After 4 weeks of treatment, 63% of the patients receiving rioprostil are endoscopically healed, compared with 72% of those receiving ranitidine. After 6 weeks of treatment, the cumulative healing rates are 86% and 93.5% respectively; this difference is statistically significant. Diarrhoea is the main adverse event, but is generally mild and self-limiting. These results indicate that rioprostil, 300 micrograms b.d., is a safe and effective treatment for duodenal ulcer, but is slightly less effective than ranitidine, 150 mg b.d.

The effect of a new specific alpha-amylase inhibitor on post-prandial glucose and insulin excursions in normal subjects and Type 2 (non-insulin-dependent) diabetic patients.

Trestatin (Ro 9-0154), a new specific alpha-amylase inhibitor of microbial origin, was tested in six normal subjects and seven Type 2 (non-insulin-dependent) diabetic patients. In normal subjects the maximal increases in blood glucose following a 115-g starch meal were 2.19 +/- 0.57 mmol/l (mean +/- SEM) with placebo, but 1.32 +/- 0.39 mmol/l with 10 mg, 1.06 +/- 0.26 mmol/l with 20 mg, 0.43 +/- 0.07 mmol/l with 50 mg (p less than 0.05) and 0.26 +/- 0.14 mmol/l with 100 mg (p less than 0.05) Trestatin . The corresponding increases in plasma insulin were 116.5 +/- 19.6 mU/l; 74.8 +/- 17.5 mU/l; 50.7 +/- 8.3 mU/l; 28.7 +/- 6.9 mU/l (p less than 0.05) and 16.5 +/- 3.2 mU/l (p less than 0.05). In the diabetic patients the maximal increases in blood glucose following a 50-g starch meal were 6.09 +/- 0.02 mmol/l with placebo, but 3.17 +/- 0.59 mmol/l (p less than 0.05) with 10 mg and 1.69 +/- 0.41 mmol/l (p less than 0.05) with 30 mg Trestatin . The corresponding insulin increases were: 58.8 +/- 12.7 mU/l, 31.5 +/- 9.7 mU/l (p less than 0.05) and 23.4 +/- 4.8 mU/l (p less than 0.05). Trestatin fully retained this pharmacological activity during treatment for 4 weeks in the diabetic patients. Trestatin did not influence glucose and insulin profiles after oral glucose and sucrose. These results are consistent with a specific inhibition of alpha-amylase in man.