A double-blind, randomized, fixed-dose trial of fluoxetine vs. amitriptyline in the treatment of major depression complicating Alzheimer''s disease

Serum-soluble HLA class I molecules (sHLA) have immunomodulatory functions and their serum levels correlate with the HLA class I phenotype. We studied longitudinal changes of serum sHLA levels in insulin-dependent diabetes mellitus (IDDM). A total of 198 serum samples were obtained from 40 IDDM patients before and after IDDM onset. sHLA was assayed by a sandwich ELISA. sHLA levels in IDDM patients at the initiation of insulin therapy (IDDM onset) were markedly reduced compared with those in normal controls (334.2 +/- 26.3 ng/ml vs 492.4 +/- 55.5 ng/ml, mean +/- SEM, P = 0.0038). They fell sharply during 6 months before and after the onset of IDDM. The dynamic profile of sHLA and the time course of beta-cell loss were different between IDDM patients with and without HLA-A24. In those with HLA-A24, sHLA became significantly lower than normal controls with HLA-A24 at IDDM onset. Recovery of their sHLA values occurred at 3 years from IDDM onset. On the other hand, in those without HLA-A24, sHLA levels began to decrease since the onset of IDDM and became significantly lower than normal controls without HLA-A24 at 4 years after the onset. Recovery of sHLA occurred at more than 6 years from the onset. An early (within 18 months), complete loss of beta-cell function occurred in 5 of 13 IDDM patients with HLA-A24 compared with 1 of 14 of those without HLA-A24 (P = 0.077). A late (more than 36 months after the onset of IDDM), complete loss of beta-cell function occurred in 7 of 14 IDDM patients without HLA-A24 but in none of 13 of those with HLA-A24 (P = 0.0058). These results indicate that the decline of sHLA is synchronous with massive beta-cell destruction, and that these events occur during a short period in IDDM patients with HLA-A24, whereas they occur during a relatively long period in those without HLA-A24.     

A double-blind, randomized, placebo-controlled trial of fluoxetine in children and adolescents with depression

BACKGROUND: Depression is a major cause of morbidity and mortality in children and adolescents. To date, randomized, controlled, double-blind trials of antidepressants (largely tricyclic agents) have yet to reveal that any antidepressant is more effective than placebo. This article is of a randomized, double-blind, placebo-controlled trial of fluoxetine in children and adolescents with depression. METHODS: Ninety-six child and adolescent outpatients (aged 7-17 years) with nonpsychotic major depressive disorder were randomized (stratified for age and sex) to 20 mg of fluoxetine or placebo and seen weekly for 8 consecutive weeks. Randomization was preceded by 3 evaluation visits that included structured diagnostic interviews during 2 weeks, followed 1 week later by a 1-week, single-blind placebo run-in. Primary outcome measurements were the global improvement of the Clinical Global Impressions scale and the Children's Depression Rating Scale--Revised, a measure of the severity depressive symptoms. RESULTS: Of the 96 patients, 48 were randomized to fluoxetine treatment and 48 to placebo. Using the intent to treat sample, 27 (56%) of those receiving fluoxetine and 16 (33%) receiving placebo were rated "much" or "very much" improved on the Clinical Global Impressions scale at study exit (chi 2 = 5.1, df = 1, P = .02). Significant differences were also noted in weekly ratings of the Children's Depression Rating Scale--Revised after 5 weeks of treatment (using last observation carried forward). Equivalent response rates were found for patients aged 12 years and younger (n = 48) and those aged 13 years and older (n = 48). However, complete symptom remission (Children's Depression Rating Scale--Revised < or = 28) occurred in only 31% of the fluoxetine-treated patients and 23% of the placebo patients. CONCLUSION: Fluoxetine was superior to placebo in the acute phase treatment of major depressive disorder in child and adolescent outpatients with severe, persistent depression. Complete remission of symptoms was rare.     

A randomized, controlled trial of amitriptyline in the acute treatment of adolescent major depression

OBJECTIVE: To determine amitriptyline's (AMI) efficacy in the acute treatment of adolescent major depressive disorder (MDD). METHOD: Subjects aged 12 through 17 years meeting Research Diagnostic Criteria for MDD, diagnosed with the Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS), participated in a 2-week placebo-washout followed by an 8-week, randomized, double-blind, parallel-design, placebo-controlled trial of AMI, 5 mg/kg per day. The K-SADS nine-item scale, the Hamilton Depression Rating Scale, and the Clinical Global Impressions rating scale were used as outcome measures. RESULTS: Thirty-one subjects were randomized (18 AMI, 13 placebo). Twenty-two subjects were study completers (12 AMI, 10 placebo). AMI's efficacy was suggested by the Clinical Global Impressions but not the K-SADS-derived data. Perhaps the primary limitation of the current study is its small sample size. CONCLUSION: No definitive recommendation can be made regarding the efficacy of tricyclic antidepressants in the treatment of adolescent MDD.     

A randomized crossover trial of levodopa in congestive heart failure

BACKGROUND: The short- and long-term effects of levodopa (L-dopa), an oral dopaminergic prodrug, were assessed in patients with severe left ventricular dysfunction. METHODS AND RESULTS: Initially, 26 patients were included in the study group. After clinical, radiographic, and radionuclide examination, each patient underwent right heart catheterization (Swan-Ganz thermodilution catheter). Plasma noradrenaline levels were measured. In two patients, a favorable hemodynamic response to L-dopa was not observed, another two required permanent pacemaker implantation. These four patients were excluded from the study. Two patients required permanent pacemaker implantation. The remaining 22 patients with favorable hemodynamic response to L-dopa (increase in cardiac index, stroke volume index, reduction in total systemic resistance) were randomized in a nonblinded fashion to the conventional (11 patients) or conventional plus L-dopa (11 patients) treatment groups. During the study period, two patients, one from each group, died. They were excluded from the analysis. The final analyzed study group consisted of 20 men, aged 33-69, in New York Heart Association functional class IV (9 patients) and III (11 patients). The cause of congestive heart failure was primary dilated cardiomyopathy in 11 patients and ischemic heart disease in 9 patients. After 3 months' treatment, all patients were crossed over. Clinical, radiographic, radionuclide, and hemodynamic evaluation was repeated at the end of the 3-month treatment period. After 3 months of therapy with L-dopa in each group (covariance analysis), there was improvement in clinical, radiographic (relative heart volume, -128 mL/m2), radionuclide (left ventricular ejection fraction, +4.6; right ventricular ejection fraction, +4.8%), hemodynamic (mean pulmonary wedge pressure, -8 mmHg; total systemic resistance, -1.8 Wu; total pulmonary resistance, -3.5 Wu), and neurohumoral (noradrenaline, -218 pg/mL) measures. CONCLUSIONS: The addition of L-dopa to conventional therapy has beneficial short- and long-term effects in patients with severe left ventricular dysfunction.     

Desmopressin in the management of nocturia in patients with multiple sclerosis. A double-blind, crossover trial

BACKGROUND: Neurogenic bladder affects up to 80% of patients with multiple sclerosis (MS) and, in 50% of these patients, it is a significant cause of disability. The current management of neurogenic bladder, based on fluid restriction, anticholinergic agents, intermittent self-catheterization, and, in some cases, surgical intervention, often fails to relieve all symptoms. Furthermore, anticholinergic drugs have significant adverse effects and may be medically contraindicated. Nocturia is a particularly disabling symptom of neurogenic bladder; by disrupting sleep patterns, it aggravates the chronic fatigue of MS, imposes serious demands on caregivers, and can lead to institutionalization. To evaluate a novel approach to the symptomatic management of nocturia in patients with MS, we have conducted a trial of desmopressin acetate (1-desamino-8-D-arginine vasopressin), a synthetic analogue of antidiuretic hormone. OBJECTIVE: To evaluate the efficacy and short-term safety of desmopressin therapy in the symptomatic treatment of nocturia in patients with MS. METHODS: Seventeen patients were enrolled in a double-blind, crossover trial of desmopressin administered at bedtime. Patients with both relapsing-remitting and chronic-progressive forms of MS were admitted. Night time voiding diaries were maintained for the 6 weeks of the trial; similarly, serum electrolyte levels and plasma osmolality were measured twice weekly and urinalyses and urine cultures were performed weekly during the trial. RESULTS: Desmopressin reduced the percentage of nights with nocturia in patients from 97% to 66%. The average number of episodes of nocturia per night in patients decreased from 2.35 to 1.09 and the maximum hours of sleep uninterrupted by nocturia increased from 3.74 to 5.77. These results were highly significant. Four of the 17 patients discontinued participation in the study after developing asymptomatic or minimally symptomatic hyponatremia. CONCLUSIONS: Desmopressin was found effective; no tolerance and only minimal adverse effects have been observed. Our results suggest that desmopressin, either alone or in combination with other therapeutic modalities, is effective in the symptomatic management of nocturia in patients with MS. The only adverse effect attributed to desmopressin was hyponatremia, which occurred in 4 of 17 patients and appeared to be dose related.     

A double-blind, randomized, placebo-controlled trial of prostaglandin E1 in liver transplantation

A double-blind placebo-controlled trial of intravenous prostaglandin PGE1 (40 micrograms/h) was conducted in adult orthotopic liver transplant recipients. Infusion was started intraoperatively and continued for up to 21 days. Patients were followed up for 180 days postoperatively. Among 172 patients eligible for treatment in the study, 160 could be evaluated (78 PGE1; 82 placebo). Patient and graft survival were similar (PGE1: 16 deaths, 9 retransplantations [7 survivors]; controls: 15 deaths, 6 retransplantations [3 survivors]). In patients with surviving grafts, however, PGE1 administration resulted in a 23% shorter mean duration of hospitalization following transplantation (PGE1: 24.4 days; controls: 31.8 days; P = .02) and a 40% shorter length of time postoperatively in the intensive care unit (PGE1: 8.2 days; controls 13.7 days; P = .05). Reduced needs for renal support (P = .03) or surgical intervention other than retransplantation (P = .02) were also noted with PGE1 use. Further, PGE1 administration resulted in a trend toward improved survival rates in patients with mild renal impairment (preoperative serum creatinine 1.5 mg percent or greater; P = .08). Neither the incidence of acute cellular rejection nor of primary nonfunction was significantly different in the two groups. Phlebitis was the only complication that was more common during PGE1 administration, (PGE1: 9; controls: 4). These results suggest that PGE1 use in hepatic allograft recipients reduces morbidity and may result in sizable cost reductions.     

Thalidomide in the treatment of the mucocutaneous lesions of the Beh?et syndrome. A randomized, double-blind, placebo-controlled trial

Mood disorders are known to cluster within families, but the mode of transmission remains largely unknown. The purpose of our analysis was to determine whether selection of a sample that was homogeneous in its response to an antidepressant provided stronger evidence for a single major locus. Complex segregation analysis was applied to a sample of 171 Italian families of bipolar and unipolar probands that were responsive to the antidepressant fluvoxamine. We used regressive logistic analyses to determine the best fit from among environmental, arbitrary Mendelian, dominant, recessive and additive models. For the 171 affective families with probands that were responsive to the antidepressant fluvoxamine, a Mendelian model of inheritance was rejected. When considering 68 families of bipolar probands, the best fit was obtained for a Mendelian dominant model of transmission. The identification of a Mendelian mode of transmission in bipolar subjects who were selected according to their response to fluvoxamine supports the use of a pharmacological criterion as a tool for identifying true genetic disorders.     

Long-term stimulant treatment of children with attention-deficit hyperactivity disorder symptoms. A randomized, double-blind, placebo-controlled trial

In this study we evaluated the effect of long-term melatonin (MEL) treatment on the cytotoxic activity and number of natural killer (NK) cells and the proliferative response of spleen lymphocytes to phytohemagglutinin (PHA) or interleukin-2 (IL-2) in old mice. Seventeen-eighteen month-old Balb/c mice were supplemented with MEL (40-50 microg/day/mouse) and sacrificed after eight months. The MEL supplementation was unable to recover the low levels of both endogenous and IL-2-induced NK cell activity found in old untreated mice. Also the NK cell number was unaffected by MEL treatment. The spleen lymphocyte proliferative response to both PHA and IL-2 was not different in old MEL-treated compared to old untreated mice. These results indicate that long-term MEL supplementation does not recover the age-related deterioration of NK cell activity and lymphocyte proliferative capacity.     

Folic acid in the treatment of acute watery diarrhoea in children: a double-blind, randomized, controlled trial

One-hundred and six male children aged 6-23 months with a history of acute watery diarrhoea of less than 72 h duration were randomized to receive either folic acid in a dose of 5 mg at 8-h intervals or placebo for 5 d. There were 54 children in the folic acid group and 52 in the placebo group. The admission characteristics were comparable between the two groups. No significant differences were observed in the intake of oral rehydration solution or stool output between the groups. The mean+/-SD of total stool output (g kg(-1)) was 532+/-476 vs 479+/-354 and the duration (h) of diarrhoea was 108+/-68 vs 103+/-53 in the folic acid vs placebo group, respectively. The findings, therefore, should have a positive influence on preventing the inappropriate use of folic acid in acute diarrhoea.     

Pergolide: treatment of choice in restless legs syndrome (RLS) and nocturnal myoclonus syndrome (NMS). A double-blind randomized crossover trial of pergolide versus L-Dopa

A double-blind randomized crossover study of 0.125 mg Pergolide (Lilly) at bedtime versus 250mg L-Dopa + Carbidopa (Roche) was conducted in 16-day phases in 11 patients with idiopathic restless legs syndrome. Two patients reported a partial and 9 patients a complete relieve of motor restlessness while receiving Pergolide. Only 1 patient experienced an improvement of restlessness after L-Dopa. The patients showed polysomnographically a mean decrease in NMS cluster disturbed time by 45% from control on L-Dopa (p < 0.025) and by 79% from control on Pergolide (p < 0.001). In addition, Pergolide increased the total sleep time compared to L-Dopa (p < 0.05). In conclusion, the dopamine agonist Pergolide is superior to L-Dopa in the treatment of RLS and NMS.     

Treatment with oral 3,4 diaminopyridine improves leg strength in multiple sclerosis patients: results of a randomized, double-blind, placebo-controlled, crossover trial

To examine the efficacy and toxicity of oral 3,4 diaminopyridine (DAP) in dosages up to 100 mg/day, 36 patients with multiple sclerosis (MS) enrolled in a randomized, double-blind, placebo-controlled, crossover trial. The primary outcome measure was improvement of a prospectively defined neurologic deficit, which was leg weakness in 34 patients. Secondary outcome measures included the patient's subjective response, scored manual motor testing (MMT) of leg strength, scored leg strength from videotaped motor testing (VMT), quadriceps and hamstrings strength (QMT) measured by isometric dynamometry, neuropsychological testing (NPT), ambulation index (AI), and Expanded Disability Status Scale (EDSS) score. Paresthesias and abdominal pain were common and were dose limiting in eight patients. Three patients had episodes of confusion, and one patient had a seizure while on DAP. Eight patients withdrew from the study, leaving 28 evaluable patients for the efficacy analysis. The prospectively defined neurologic deficit improved in 24 patients-22 on DAP and 2 on placebo (p = 0.0005). All improvements were in leg weakness. Subjective response and measures of leg strength and function (MMT, VMT, QMT, and AI) improved on DAP compared with placebo. Neither NPT nor EDSS scores improved. DAP treatment can induce improvements in leg strength in MS patients, but toxicity is limiting in many patients.     

Short-chain fatty acids in the treatment of radiation proctitis: a randomized, double-blind, placebo-controlled, cross-over pilot trial

PURPOSE: Treatment of chronic radiation proctitis remains unsatisfactory. Short-chain fatty acids are the preferred energy source for the colonic epithelium. We aimed to determine for the first time whether topical butyric acid enemas relieve symptoms and improve the macroscopic and microscopic findings in chronic radiation proctitis. METHODS: A randomized, double-blind, placebo-controlled, cross-over pilot trial compared patients given two weeks of butyric acid enemas (40 mmol) twice per day with those given placebo, with a one-week washout period; 15 patients were randomized and 12 completed both arms of the trial. A total symptom score combined six symptom items per week (rectal pain, episodes of rectal bleeding, amount of blood passed, days with diarrhea, number of stools, and urgency). Symptom, endoscopic, and histologic scores were obtained at the beginning of the study and again at the last week of each treatment arm. RESULTS: Total symptom score at baseline (median, 5.5) improved for those patients receiving active treatment (median, 3.5), but compared with placebo (median, 4.5), the change was not significant. Endoscopic appearances were largely unaltered by active treatment. Histology was abnormal in 82 percent of patients receiving placebo compared with 55 percent of those given butyric acid enemas (P = not significant). CONCLUSION: Butyric acid enemas do not appear to be superior to placebo in the treatment of chronic radiation proctitis.     

Corticosteroids in the treatment of tuberculous pleurisy. A double-blind, placebo-controlled, randomized study

Although several studies on tuberculous (TB) pleurisy suggest that the addition of corticosteroids to anti-TB therapy may have beneficial effects, these agents are not used routinely. To assess the effects of short-term oral prednisone therapy in TB pleurisy, 74 patients were randomly assigned in a double-blind fashion to treatment with either placebo or prednisone at a dose of 0.75 mg/kg/d for up to 4 weeks with gradual reduction over an additional 2 weeks. All subjects received a standard 3-drug anti-TB chemotherapy regimen for 6 months. TB pleurisy was diagnosed by histologic study and/or culture of pleural biopsy specimens obtained at thoracoscopy. Complete drainage of the effusion was performed simultaneously. Outcome measures were assessed periodically for 24 weeks, including indexes of morbidity and pleural thickening. After randomization, four patients were excluded from the final analysis. Of the 70 patients analyzed, 34 received prednisone and 36 received placebo. Demographic and clinical characteristics of the treatment groups were comparable at the time of hospital admission. Although a statistically significant improvement in symptoms occurred earlier in the prednisone group (8 weeks) than in the placebo group (12 weeks), between-group comparison showed no significant differences at any of the follow-up evaluations. The proportion of subjects in the prednisone group (53.1%) with residual pleural thickening at 6 months did not differ significantly from that of the placebo group (60%). Pleural effusions did not recur in any of the patients. Initial complete drainage of the effusion was associated with greater symptomatic improvement than any subsequent therapy. We conclude that standard anti-TB therapy and early complete drainage is adequate for the treatment of TB pleurisy. The addition of short-term oral prednisone therapy neither results in clinically relevant earlier symptom relief nor confers a beneficial effect on residual pleural thickening.     

A double-blind, randomized, comparative trial of itraconazole versus terbinafine for 2 weeks in tinea capitis

In this randomized, double-blind study, the efficacy and safety of oral itraconazole (n = 28) and terbinafine (n = 27), each given for 2 weeks, was compared in patients with tinea capitis. Trichophyton violaceum was the major pathogen in both groups (82.1% and 88.9%, respectively). The final evaluation at week 12 showed a cure rate of 85.7% and 77.8%, respectively (P > 0.05). Adverse events noted were mild and did not warrant discontinuation of therapy.     

A randomized double-blind trial comparing cibenzoline and disopyramide in the prevention of recurrences of atrial tachyarrhythmia

The aim of this multicenter, randomised, double-blind trial was to compare the efficacy and tolerance of oral disopyramide (D: 250 mg slow release twice daily) compared with cibenzoline (C: 130 mg twice daily) in the prevention of recurrences of atrial arrhythmias over a 6 month period. Sixty patients (mean age: 62 +/- 14 years; 37 men, 23 women; cardiac disease in 60% of cases) were randomised to two groups: C (N = 31) and D (N = 29). The commonest arrhythmia was atrial fibrillation (83%). The arrhythmia was recent (< 3 months) in 41% of patients and present for more than one year in 38% of patients. Sixteen patients of Group C (52%) and 11 of Group D (38%) had recurrences after an average of 79 +/- 58 days for Group C and 58 +/- 40 days for Group D (p = NS). The probability of absence of recurrence at 6 months was 36 +/- 11% in Group C and 55 +/- 10% in Group D (p = NS). Four patients in Group C (13%) and 13 patients in Group D (45%) had at least one unwanted side-effect (p = 0.009). Treatment was stopped because of side-effects in 2 patients in group C (6%) and 6 patients in Group D (21%). These results show that cibenzoline has a comparable efficacy for the prevention of recurrence of atrial tachyarrhythmia and is significantly better tolerated than disopyramide. This differences is mainly related to the marked anticholinergic effects of disopyramide.     

A double-blind study of paroxetine, fluoxetine, and placebo in outpatients with major depression

Human milk has a higher concentration of nucleotides than bovine milk which is the source of most infant formulas. As the composition of human milk is considered the 'gold standard,' an increasing number of infant formulas are supplemented with nucleotides. This review summarises the biology of human milk nucleotides and evaluates the studies which investigated the clinical benefits of feeding infants with nucleotide-supplemented formulas. Although dietary nucleotides have been suggested to have beneficial gastrointestinal and immunological effects, nucleotide-supplemented formula feeding has not been shown to confer the same benefits as breast feeding, and randomised controlled trials have yet to prove that healthy term infants fed nucleotide-supplemented formulas compared to those fed nonsupplemented formulas, have accelerated physical growth and neurological development, better growth and development of their gastrointestinal tract resulting in improved digestive and absorptive functions, enhanced development of their immune system resulting in increased resistance to infection and lower bacterial and viral infection rates during infancy, and a more favourable intestinal microflora associated with a lower rate of infectious diarrhoea. However, a randomised controlled trial has reported that term infants with severe intrauterine growth retardation do have better catch-up growth with nucleotide supplementation. The hypothesis that nucleotides are semi-essential nutrients needs to be further studied, in particular in the presence of prematurity, fetal growth retardation, intestinal injury and limited nutrient intake. As no deleterious effects have been reported with the use of nucleotide-supplemented formulas, the first of which was introduced over 30 years ago, such products are considered safe when nucleotides are supplemented to an amount equivalent to the free nucleotide concentration of human milk. More basic and clinical research studies are awaited to further define the biology and role of human milk nucleotides, and to critically assess the potential benefits and appropriate level of nucleotide supplementation of infant formula.     

The combination of oral lysine-acetylsalicylate and metoclopramide compared with oral sumatriptan in the treatment of migraine attacks. A randomized, double-blind, placebo-controlled clinical trial

A combination of lysine acetylsalicylate (equivalent to 900 mg aspirin) and 10 mg metoclopramide (LAS + MTC) was compared with oral sumatriptan (100 mg) and placebo in 421 patients with migraine in a randomized, double-blind, clinical trial. LAS + MTC was as effective as sumatriptan with a decrease in headache from severe or moderate to mild or none in 57% and 53%, respectively, for the first migraine attack treated, the primary efficacy parameter. Both treatments were better than placebo (success rate 24%, p < 0.001). LAS + MTC was better tolerated than sumatriptan (adverse events in 18% and 28%, respectively, p < 0.05).     

A randomized, double-blind trial for stress ulcer prophylaxis shows no evidence of increased pneumonia

AIMS: To characterise milk/plasma (M/P) ratio and infant exposure, for sertraline and N-desmethylsertraline, in breast-feeding women taking sertraline for the treatment of depression. METHODS: Eight women (mean age 28 years) taking sertraline (1.05 mg kg(-1) day(-1)) and their infants (mean age 5.7 months) were studied. Sertraline and N-desmethylsertraline in plasma and milk were measured by high-performance liquid chromatography over a 24 h dose interval at steady-state. M/P values were estimated from area under the plasma and milk concentration-time curves. All milk produced was collected over the dose interval. Infant exposure was estimated as the product of actual or estimated milk production, and average drug concentration in milk, normalized to body weight and expressed as a percentage of the weight-adjusted maternal dose. RESULTS: Mean milk production was 321 ml day(-1) (range 34-974 ml). Mean M/P values of 1.93 and 1.64 were calculated for sertraline and N-desmethylsertraline respectively. Infant exposure estimated from actual milk produced was 0.2% and 0.3% of the weight-adjusted maternal dose for sertraline and N-desmethylsertraline (as sertraline equivalents) respectively. When calculated from estimated milk production (0.15 l kg(-1) day(-1)), infant exposure was significantly greater (P<0.0001) at 0.90% and 1.32% for sertraline and N-desmethylsertraline respectively. Neither sertraline nor its N-desmethyl metabolite could be detected in plasma samples from the four infants tested. No adverse effects were observed in any of the eight infants and all had achieved normal developmental milestones. CONCLUSIONS: Irrespective of the method of calculation of infant exposure, the mean total dose of sertraline and its N-desmethyl metabolite transmitted to infants via breast-feeding is low and unlikely to cause any significant adverse effects.     

Treatment of acute cortical infarct with intravenous glycerol. A double-blind, placebo-controlled randomized trial

BACKGROUND AND PURPOSE: This clinical trial investigates the effectiveness of intravenous glycerol therapy in patients with acute cortical infarction in whom intracerebral hemorrhage was rigorously excluded. METHODS: Within 48 hours of symptoms from their first ischemic stroke, 113 hospital inpatients were randomized into the trial, provided that hemorrhage was excluded by computed tomography and informed consent was obtained. Patients were stratified into alert, semicoma, and coma groups using the Glasgow Coma Scale. Treatment was allocated according to a double-blind, randomized protocol; 56 patients received 500 mL of 10% glycerol in saline over 4 hours on 6 consecutive days, and 57 patients received corresponding placebo treatment with saline. Using a variety of objective scoring systems, patient follow-up was up to 6 months. RESULTS: Corresponding measures of outcome in the glycerol and placebo groups were similar. At 6 months, respective mortality rates were 17 of 56 and 16 of 57, and mean +/- SD improvements in scores were 9.98 +/- 14.40 vs 10.51 +/- 12.68 (long-term), 1.12 +/- 7.20 vs 1.57 +/- 6.30 (prognostic), -1.94 +/- 5.53 vs -2.06 +/- 5.34 (Glasgow Coma Scale), and 21.72 +/- 23.40 vs 11.94 +/- 18.10 (Barthel Index rating in survivors). Hemolysis (generally subclinical) was the only adverse effect. CONCLUSIONS: There was no clinically or statistically significant difference in outcome between the groups; a trend toward greater functional recovery among survivors was evident after treatment with glycerol.