[Use of prostacyclin in patients with ischemic stroke. A double-blind method II]. Double-blind controlled trial of the therapeutic effects of prostacyclin in patients with completed ischaemic stroke. Double-blind controlled trial of prostacyclin in cerebral infarction. Intravenous prostacyclin in acute nonhemorrhagic stroke: a placebo-controlled double-blind trial. Randomized controlled trial of aerosolized prostacyclin therapy in children with acute lung injury. Treatment of primary pulmonary hypertension with continuous intravenous prostacyclin (epoprostenol). Results of a randomized trial. Intra-arterial prostacyclin compared to Praxilene in the management of severe lower limb ischaemia: a double blind trial. Intra-arterial prourokinase for acute ischemic stroke. The PROACT II study: a randomized controlled trial. Prolyse in Acute Cerebral Thromboembolism. A double blind placebo controlled trial of intravenous prostacyclin (PGI2) in 108 patients with ischaemic peripheral vascular disease.
Thirty patients with acute ischaemic stroke were allocated randomly into a group treated with prostacyclin and a group receiving placebo. The treatment was started 24 to 72 hours after the onset of stroke. Prostacyclin sodium (Wellcome, U.K. or Chinoin, HPR) or its solvent (glycine buffer) were administered intravenously once daily during 2 weeks in 6-hour infusions. Prostacyclin was infused at rates of 2.5-5.0 ng/kg/min. Statistically significant improvement appeared from the second day on in the prostacyclin group, and only from the eighth day on in the placebo group. However, the final improvement was not statistically different between these groups. In a pilot study, 26 patients with acute completed strokes (48 hours to 5 days after cerebral infarction) were randomly assigned to the prostacyclin (PGI2) or placebo groups. PGI2 sodium salt (Epoprostenol, Wellcome Research Laboratories and Upjohn Company) or its solvent (glycine buffer) were infused into the subclavian vein for six-hour periods in five courses separated by six-hour intervals. Prostacyclin was administered at a rate of 2.5-5.0 ng/kg/min. A significant alleviation of neurological deficits occurred 6 and 54 hours after the treatment in patients receiving prostacyclin. This improvement lost its statistical significance at the end of a two-week observation period. It is concluded that further modified controlled studies are required to evaluate the therapeutic usefulness of PGI2 in the treatment of patients with cerebral ischaemia. Thirty-two patients with acute cerebral infarction received either prostacyclin or placebo intermittently for 65 hours. Pulse and blood pressure were not altered by prostacyclin. After infusion there was no change in infarct volume or cerebral blood flow in either group. After normalisation for starting values, age and site of cerebral infarction there was a greater than 10% improvement in speech in the prostacyclin group, but minimal changes in neurological score or disability status. Age is related to neurological score at 14 days after stroke by decreasing improvement by 6.8% for each additional 10 years. This study has not been able to demonstrate that prostacyclin is effective in the treatment of ischaemic stroke, but due to the sample size the chance of proving this statistically (the power) was small. Similarly any conclusion that prostacyclin is not effective may be wrong because of the Type II error probability being high. The therapeutic efficacy of prostacyclin in nonhemorrhagic cerebral infarction was assessed in a placebo-controlled double-blind trial. A total of 80 patients with stroke onset within 24 hours were randomized into placebo (37 patients) and prostacyclin (43 patients) groups. Demographic data and risk factors were comparable. Patients in the prostacyclin group received a continuous i.v. infusion of prostacyclin at an average rate of 8.5 ng/kg/min for an average of 64 hours. The placebo group received vehicle only in a similar fashion. During treatment hemodynamic changes were more prominent in the patients receiving prostacyclin and included reduction of systolic and diastolic blood pressure and increase in pulse rate. In contrast there was only a slight (but significant) reduction of diastolic blood pressure in the placebo group. Neurologic deficit scores were determined on admission, at Day 3, and at Weeks 1, 2, and 4. Mean neurologic deficit scores upon entry were comparable in the placebo and prostacyclin groups, and a significant improvement in the score for neurologic deficit was noted in both. The placebo group tended to fare better throughout the study, with a significant difference in neurologic deficit score favoring the placebo group at Week 2 (p = 0.0048). Two patients in the placebo and one in the prostacyclin group died. The only difference in adverse reactions was flushing (6 patients in prostacyclin vs. 0 in placebo group, p less than 0.05). The results of this study suggest a lack of therapeutic efficacy of prostacyclin in a defined population of patients with nonhemorrhagic cerebral infarction. To investigate whether aerosolized prostacyclin improves oxygenation in children with acute lung injury.
                Double-blind, randomized, and placebo-controlled trial.
                Pediatric intensive care unit at a university hospital.
                Fourteen children with acute lung injury defined by the criteria of an American-European Consensus Conference.
                Aerosolized prostacyclin (epoprostenol sodium) by stepwise increments of different doses (10, 20, 30, 40, and 50 ng x kg x min) vs. aerosolized normal saline (placebo).
                Before the start of the study, and before and after each dose of prostacyclin/placebo, the following variables were measured: arterial blood gases, heart rate, mean arterial blood pressure, and ventilator settings required. Changes in oxygenation were measured by calculation of the oxygenation index (mean airway pressure x 100 x Pao2/Fio2). After treatment with aerosolized prostacyclin, there was a significant 26% (interquartile range, 3%, 35%) improvement in oxygenation index at 30 ng x kg x min compared with placebo (p =.001). The response to prostacyclin was not the same in all children. We saw an improvement of > or = 20% in eight of 14 children (i.e., responders), and the number needed to treat was 1.8 (95% confidence interval, 1.2-3.2). No adverse effects were observed.
                Aerosolized prostacyclin improves oxygenation in children with acute lung injury. Future trials should investigate whether this treatment will positively affect outcome. To determine the efficacy of continuous intravenous infusion of prostacyclin (epoprostenol) in primary pulmonary hypertension.
                Randomized trial with 8-week treatment periods and nonrandomized treatment for up to 18 months.
                Four referral centers.
                Sequential sample of 24 patients with primary pulmonary hypertension. Nineteen patients completed the study. Four patients died and one left the study because of adverse effects (pulmonary edema).
                Continuous intravenous prostacyclin administered by portable infusion pump at doses determined by acute responses during baseline catheterization in ten patients. Nine patients were treated with anticoagulants, oral vasodilators, and diuretics.
                Starting with a baseline value for total pulmonary resistance of 21.6 units, there was a decrease of 7.9 units (95% CI, -13.1 to -2.2; P = 0.022) in the prostacyclin-treated group after 8 weeks; there was virtually no change in the conventional therapy group (from 20.6 to 20.4 units, not significant). Six of ten prostacyclin-treated patients who completed the 8-week study period had reductions in mean pulmonary artery pressure of greater than 10 mm Hg, whereas only one of nine in the conventional treatment group had a similar response (P = 0.057). Nine patients receiving prostacyclin for up to 18 months have persistent hemodynamic effects, although dose requirements have increased with time. Complications have been attributable to the drug delivery system.
                Prostacyclin produces substantial and sustained hemodynamic and symptomatic responses in severe primary pulmonary hypertension and may be useful in the management of some patients with this disease. The effectiveness of a 72 h. intra-arterial prostacyclin infusion has been compared to that of naftidrofuryl oxalate (Praxilene) in a double blind study of 29 patients with ischaemic rest pain in 30 legs. Long-term relief of symptoms was achieved in 14 legs (47%) and major limb amputation avoided in 18 (60%). No significant difference was demonstrated between the results of prostacyclin infusion and those of Praxilene. Intravenous tissue-type plasminogen activator can be beneficial to some patients when given within 3 hours of stroke onset, but many patients present later after stroke onset and alternative treatments are needed.
                To determine the clinical efficacy and safety of intra-arterial (IA) recombinant prourokinase (r-proUK) in patients with acute stroke of less than 6 hours' duration caused by middle cerebral artery (MCA) occlusion.
                PROACT II (Prolyse in Acute Cerebral Thromboembolism II), a randomized, controlled, multicenter, open-label clinical trial with blinded follow-up conducted between February 1996 and August 1998.
                Fifty-four centers in the United States and Canada.
                A total of 180 patients with acute ischemic stroke of less than 6 hours' duration caused by angiographically proven occlusion of the MCA and without hemorrhage or major early infarction signs on computed tomographic scan.
                Patients were randomized to receive 9 mg of IA r-proUK plus heparin (n = 121) or heparin only (n = 59).
                The primary outcome, analyzed by intention-to-treat, was based on the proportion of patients with slight or no neurological disability at 90 days as defined by a modified Rankin score of 2 or less. Secondary outcomes included MCA recanalization, the frequency of intracranial hemorrhage with neurological deterioration, and mortality.
                For the primary analysis, 40% of r-proUK patients and 25% of control patients had a modified Rankin score of 2 or less (P = .04). Mortality was 25% for the r-proUK group and 27% for the control group. The recanalization rate was 66% for the r-proUK group and 18% for the control group (P<.001). Intracranial hemorrhage with neurological deterioration within 24 hours occurred in 10% of r-proUK patients and 2% of control patients (P = .06).
                Despite an increased frequency of early symptomatic intracranial hemorrhage, treatment with IA r-proUK within 6 hours of the onset of acute ischemic stroke caused by MCA occlusion significantly improved clinical outcome at 90 days. 108 patients with ischemic peripheral vascular disease were randomly allocated to receive infusion of either PGI2 (6 ng/kg/min over 8 hours daily for 5 consecutive days) or placebo in a double-blind manner. All patients had Stage II disease (Fontaine classification). One month after infusion the absolute and relative walking times were significantly (p less than 0.05) longer in the PGI2- than in the placebo-treated group. Patients were further classified as treatment responders or non-responders on the basis of increase of absolute and relative walking times. After one month 44% (24 out of 54) of the PGI2- and 15% (8 out of 54) of the placebo-treated patients were positive treatment-responders (p less than 0.01).
Too few patients have been studied in randomised trials to allow conclusions to be drawn about the effect of prostacyclin treatment on survival of people with acute stroke.