Artesunate and praziquantel for the treatment of Schistosoma haematobium infections: a double-blind, randomized, placebo-controlled study.

Recently, artemisinin derivatives have been shown to be efficacious in chemoprophylaxis of and chemotherapy for Schistosoma japonicum and S. mansoni infections. Therefore, a double-blind, randomized, placebo-controlled study was carried out to investigate the efficacy and tolerability of artesunate plus placebo and the combination of artesunate and praziquantel in the treatment of S. haematobium infections in Gabon. The 300 infected schoolchildren included in the study were randomized to receive artesunate plus placebo (n=90), praziquantel plus placebo (n=90), artesunate and praziquantel (n=90), or only placebo (n=30). End points were efficacy, assessed as cure on day 56, and tolerability. All treatment regimens were well tolerated. The praziquantel plus placebo-treated group attained a cure rate of 73%, artesunate plus placebo a rate of 27%, the combination of artesunate and praziquantel a rate of 81%, and placebo alone a rate of 20%. In summary, earlier findings of efficacy of artemisinin derivitives against S. mansoni and S. japonicum could not be confirmed in S. haematobium infections.     

Oral artemether for prevention of Schistosoma mansoni infection: randomised controlled trial

This randomized, double-blind placebo-controlled trial examined the efficacy of oral artemether for the prevention of Schistosoma mansoni infection among 354 children from Cote d'Ivoire. Stool specimens were screened over 4 consecutive days, followed by two mass treatments with praziquantel 4 weeks apart. All S. mansoni negative children were randomly assigned to placebo (n = 151) or artemether (n = 138). An assessment after 24 hours and examination of blood samples after the 3rd week of initial administration was conducted. Findings revealed that administration of oral artemether showed no adverse reaction, with an observation of a relatively lower incidence of S. mansoni infection (31/128 vs. 68/140; relative risk, 0.50; 95% confidence interval, 0.35-0.71; p = 0.00006). In addition, the geometric mean egg output among positive children in the artemether group was significantly lower in placebo treatment (19 vs. 32 eggs/g stool; p = 0.017). Furthermore, there was a significant reduction in the prevalence of Plasmodium falciparum. The study confirmed the safety and prophylactic effect of oral artemether against S. mansoni, and recommends its use as an additional tool for a more effective schistosomiasis control measure.     

Randomized, double-blind, placebo-controlled glucosamine discontinuation trial in knee osteoarthritis

OBJECTIVE: To assess the efficacy of glucosamine sulfate in knee osteoarthritis (OA). METHODS: A 4-center, 6-month, randomized, double-blind, placebo-controlled glucosamine discontinuation trial was conducted in 137 current users of glucosamine with knee OA who had experienced at least moderate improvement in knee pain after starting glucosamine. Study medication dosage was equivalent to the dosage of glucosamine taken prior to the study (maximum 1,500 mg/day). Followup continued for 6 months or until disease flare, whichever occurred first. The primary outcome was the proportion of disease flares in the glucosamine and placebo groups using an intent-to-treat analysis. Secondary outcomes included time to disease flare; analgesic medication use; severity of disease flare; and change in pain, stiffness, function and quality of life in the glucosamine and placebo groups. RESULTS: Disease flare was seen in 28 (42%) of 66 placebo patients and 32 (45%) of 71 glucosamine patients (difference -3%; 95% confidence interval [95% CI] -19, 14; P = 0.76). In the Cox regression analysis, after adjustment for sex, study site, and OA radiographic severity, time to disease flare was not significantly different in the glucosamine compared with placebo group (hazard ratio of flare = 0.8; 95% CI 0.5, 1.4; P = 0.45). At final study visit, acetaminophen was used in 27% and 21% of placebo and glucosamine patients, respectively (P = 0.40), nonsteroidal antiinflammatory drugs were used in 29% and 30% (P = 0.92), and both were used in 20% and 21% (P = 0.84). No differences were found in severity of disease flare or other secondary outcomes between placebo and glucosamine patients. CONCLUSION: In patients with knee OA with at least moderate subjective improvement with prior glucosamine use, this study provides no evidence of symptomatic benefit from continued use of glucosamine sulfate.     

Randomized, double-blind, placebo-controlled trial of corticosteroids after Kasai portoenterostomy for biliary atresia

The objective of this study was to evaluate adjuvant corticosteroids after Kasai portoenterostomy for biliary atresia. The study consisted of a prospective, 2-center, double-blind, randomized, placebo-controlled trial of post-Kasai portoenterostomy corticosteroids (oral prednisolone: 2 mg/kg/day from day 7 to day 21 and 1 mg/kg/day from day 22 to day 28). The data were compared with chi2 or Mann-Whitney tests, as appropriate. Seventy-one postoperative infants with type 3 biliary atresia were randomized to receive either oral prednisolone (n = 36) or a placebo (n = 37). At 1 month, the median bilirubin level was lower in the steroid group (66 versus 92 micromol/L, P = 0.06), but no difference was evident at 6 (P = 0.56) or 12 (P = 0.3) months. The proportion of infants with a normal bilirubin level (<20 micromol/L) at 6 (47% versus 49%, P = 0.89) and 12 months (50% versus 40%, P = 0.35) was not significantly different. The need for transplantation by 6 (12% versus 13%, P = 0.99) and 12 months (26% versus 35%, P = 0.47) was not significantly different. The steroid effect was more pronounced in younger infants (less than 70 days at Kasai portoenterostomy, n = 51), with a reduced bilirubin level at 1 month (64 versus 117 micromol/L, P = 0.01) and with a greater proportion with a normal bilirubin level at 12 months (54% versus 37%, P = 0.22). CONCLUSION: There was a beneficial effect on the rate of reduction of bilirubin in the early postoperative period (specifically in infants less than 70 days old at surgery), but this steroid regimen did not reduce the need for liver transplantation.     

Randomized, double-blind, placebo-controlled trial of long-acting release octreotide for treatment of Graves' ophthalmopathy

CONTEXT: Despite a strong rationale for trials of somatostatin analogs in the treatment of Graves' ophthalmopathy (GO), recent studies have provided conflicting results. OBJECTIVE: The objective of the study was to determine whether octreotide long-acting release (LAR) is effective treatment for active GO. DESIGN: This was a prospective, randomized, double-blind, placebo-controlled study. SETTING: The setting was a single tertiary referral center. PATIENTS: Twenty-nine consecutive euthyroid patients with active GO [clinical activity score (CAS) >or= 3] were enrolled; 25 completed the study. INTERVENTION: Patients received four monthly doses of either octreotide LAR (20 mg) or saline by im injections. MAIN OUTCOME MEASURES: Primary measure was a change in CAS; the secondary measure was changes in retrobulbar tissue volume, proptosis, lid fissure width, range of motion, and diplopia fields. RESULTS: Median (range) CAS change was 2.5 (1, 5) in the treatment and 1.0 (0, 7) in the placebo group (P = 0.02). Median lid fissure width improved in the treatment group, (decreased 1 mm on the right and 0.5 mm on the left), compared with the placebo group (no change on the right, P < 0.01; increased 1 mm on the left, P < 0.01). No other significant differences between groups were identified. CONCLUSIONS: CAS improved to a greater extent in octreotide-LAR-treated patients than the control group. However, this finding may not represent clinical benefit because patients with higher baseline CAS were overrepresented in the treatment group, and the control group was small. In contrast, treatment-related improvement in eyelid fissure width was noted, suggesting that octreotide LAR may be useful in the treatment of a subgroup of active GO patients with significant lid retraction.     

Randomized, double-blind, placebo-controlled trial of tissue plasminogen activator in unstable angina

Angiographic, angioscopic and pathologic reports have recently demonstrated a high incidence of intracoronary thrombus in patients with unstable angina. To determine if thrombolysis could be beneficial when combined with maximal medical therapy, 40 patients with rest angina, angiographically documented coronary artery disease and pacing-induced ischemia were randomly assigned to intravenous recombinant tissue-type plasminogen activator (rt-PA, 150 mg/8 h) or placebo in a prospective double-blind trial. All patients received nitrates, a beta-adrenergic blocking agent, a calcium channel blocker, aspirin and heparin. Pacing thresholds for ischemia and quantitative coronary stenosis were measured before and after infusion of the study medication. Intracoronary thrombus was identified angiographically before infusion of the study medication in 16 patients; 7 received rt-PA and 9 received placebo. The ischemic pacing threshold in patients treated with rt-PA increased from 112 +/- 4 beats/min at baseline to 127 +/- 5 beats/min (p = 0.007) by the end of the infusion versus an insignificant change in patients who received placebo (from 116 +/- 4 to 119 +/- 4 beats/min, p = NS). In patients with intracoronary thrombus, the ischemic pacing threshold increased 26 +/- 7 beats/min with rt-PA treatment versus 0 +/- 3 beats/min with placebo (p = 0.004). In contrast, in patients without thrombus, there was no difference in ischemic pacing threshold increments between treatment groups (7 +/- 11 beats/min for rt-PA versus 6 +/- 5 beats/min for placebo, p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)     

A double-blind,placebo-controlled trial

Sulfasalazine (SSZ), 3 gm daily, was compared with placebo for treatment of rheumatoid arthritis, in a 15-week randomized, parallel, double-blind trial. Joint tenderness and swelling, morning stiffness, grip strength, and pain score all showed significantly more improvement with SSZ than with placebo. Adverse effects, particularly gastrointestinal reactions, led to withdrawal from the study of 28% of the patients who had been receiving SSZ, but these effects were all readily reversible and not life-threatening. These results confirm previous findings that suppression of rheumatoid synovitis may be induced by SSZ, within 2 months after full maintenance doses are reached.     

Randomized,double-blind,placebo-controlled crossover trial of pirenzepine in patients with gastroesophageal reflux

A muscarinic receptor subtype 1 (M1) antagonist, pirenzepine, recently has been shown to be relatively free of the usual anticholinergic side effects on esophageal smooth muscle and thus has been implicated for the treatment of gastroesophageal reflux disease (GERD). However, the effect of pirenzepine on GERD remains to be defined. Thirteen patients who demonstrated GERD in a baseline 24-hr ambulatory intraesophageal pH monitoring study were randomized in a double-blind crossover fashion to receive pirenzepine and placebo. An ambulatory 24-hr intraesophageal pH monitor was used to assess reduction in reflux (esophageal pH less than 4.0) with respect to position (upright vs supine), to total number of reflux episodes, and to episodes greater than 5 min. A significant effect for pirenzepine was seen for episodes greater than 5 min (t = 2.61, P = 0.023) and a trend towards significance was seen for total (upright and supine positions combined) percent time of reflux (t = 2.13, P = 0.055). Although not statistically significant, pirenzepine consistently showed greater reduction in all parameters of reflux tested. A greater reduction in percent time of reflux in supine vs upright positions (pirenzepine: 58.9% vs 21.4%; placebo: 43.6% vs 7.3%) may be clinically important in prevention of esophageal injury due to reflux in the recumbent position. Pirenzepine may provide a unique alternative for some GERD patients who may be refractory to other therapies of GERD.     

Randomized, double-blind, placebo-controlled crossover trial of cimetidine and pirenzepine in nonulcer dyspepsia

Nonulcer dyspepsia remains a difficult disorder to treat because it is a heterogeneous syndrome. Once patients with the irritable bowel syndrome, esophagitis, and other organic diseases are excluded, there remain patients with dyspepsia of unknown cause (termed "essential dyspepsia") and patients with dyspepsia plus symptoms of gastroesophageal reflux without esophagitis. The aim of this study was to determine whether cimetidine or pirenzepine is efficacious in relieving the symptoms of these latter subgroups. Sixty-two consecutive patients were studied who had chronic upper abdominal pain or nausea where endoscopy had shown no evidence of peptic ulceration, esophagitis, or malignancy; 47 had essential dyspepsia, and 15 had dyspepsia plus gastroesophageal reflux. They were initially randomized to either cimetidine or placebo, or pirenzepine or placebo. Patients continued each medication for 1 mo, and, after a washout period, crossed over when again symptomatic; 51 patients completed cimetidine and placebo, and 50 completed pirenzepine and placebo. The results showed that cimetidine was superior to placebo in decreasing the number of upper abdominal pain episodes weekly and the severity of pain, but the absolute improvement was small. Pirenzepine was not superior to placebo in decreasing symptoms.     

Estrogen in the prevention of atherosclerosis. A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Although observational studies suggest that estrogen replacement therapy (ERT) reduces cardiovascular morbidity and mortality in postmenopausal women, use of unopposed ERT for prevention of coronary heart disease in healthy postmenopausal women remains untested. OBJECTIVE: To determine the effects of unopposed ERT on the progression of subclinical atherosclerosis in healthy postmenopausal women without preexisting cardiovascular disease. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: University-based clinic. PATIENTS: 222 postmenopausal women 45 years of age or older without preexisting cardiovascular disease and with low-density lipoprotein cholesterol levels of 3.37 mmol/L or greater (>/=130 mg/dL). INTERVENTION: Unopposed micronized 17beta-estradiol (1 mg/d) or placebo. All women received dietary counseling. Women received lipid-lowering medication if their low-density lipoprotein cholesterol level exceeded 4.15 mmol/L (160 mg/dL). MEASUREMENTS: The rate of change in intima-media thickness of the right distal common carotid artery far wall in computer image processed B-mode ultrasonograms obtained at baseline and every 6 months during the 2-year trial. RESULTS: In a multivariable mixed-effects model, among women who had at least one follow-up measurement of carotid intima-media thickness (n = 199), the average rate of progression of subclinical atherosclerosis was lower in those taking unopposed estradiol than in those taking placebo (-0.0017 mm/y vs. 0.0036 mm/y); the placebo-estradiol difference between average progression rates was 0.0053 mm/y (95% CI, 0.0001 to 0.0105 mm/y) (P = 0.046). Among women who did not receive lipid-lowering medication (n = 77), the placebo-estradiol difference between average rates of progression was 0.0147 mm/y (CI, 0.0055 to 0.0240) (P = 0.002). Average rates of progression did not differ between estradiol and placebo recipients who took lipid-lowering medication (n = 122) (P > 0.2). CONCLUSIONS: Overall, the average rate of progression of subclinical atherosclerosis was slower in healthy postmenopausal women taking unopposed ERT with 17beta-estradiol than in women taking placebo. Reduction in the progression of subclinical atherosclerosis was seen in women who did not take lipid-lowering medication but not in those who took these medications.     

Randomized double-blind, placebo-controlled trial of oral atenolol in patients with unexplained syncope and positive upright tilt table test results

The objective of this investigation was the assessment of the response rate of oral atenolol in patients with vasovagal syncope after 1 month of treatment. We randomized into two groups all patients referred to our unit who had had at least one episode of syncope or two episodes of presyncope 1 month before presentation and had a positive isuprel Tilt Table Test (TTT). Group 1 (Gr 1) received oral atenolol, and group 2 (Gr 2) received placebo medication. After a 1-month period patients were reassessed for degree of their symptoms and underwent repeated TTT. Forty-two patients were enrolled in the study. Gr 1 and Gr 2 were comparable in age (38 ± 13 years vs 43 ± 14 years, p = 0.216 and sex (male/female = 6:15 vs 10:11, p = 0.204). The severity of attack was similar in both groups. Eight patients in Gr 1 and six patients in Gr 2 had mitral valve prolapse (p = 0.5). No significant differences were seen in systolic blood pressure (122 ± 17 vs 117 ± 16 mm Hg, p = 0.334), diastolic blood pressure (70 ± 11 vs 72 ± 11 mm Hg, p = 0.677), and heart rate (79 ± 12 vs 79 ± 13, p = 0.98) between the two groups. The response rates (negative TTT) after 1 month of treatment were 62% versus 5% (p = 0.0004) in the atenolol and control group, respectively. Moreover, patients who received atenolol reported feeling better compared with those who received placebo (71% vs 29%, p = 0.02). In conclusion, atenolol significantly improved symptoms of patients with vasovagal syncope. Patients who received atenolol were more likely to have negative isuprel TTT.     

Randomized, placebo-controlled clinical trial of oral azithromycin prophylaxis against respiratory infections in a high-risk, young adult population.

Military Special Forces trainees undergo intense psychological and physical stressors that often lead to respiratory infection. During 1998-2000, 477 Navy Special Forces trainees were enrolled in a double-blind trial of oral azithromycin (1 g given weekly) plus a placebo injection, compared with benzathine penicillin G (1.2 million U) plus azithromycin placebo tablets. Among the 464 subjects with complete data, 44 developed acute respiratory infection (20 with pneumonia) during the 2 weeks of most intense training; of these subjects, 12 (27.3%) had evidence of Chlamydia pneumoniae infection and 7 (15.9%) had evidence of Mycoplasma pneumoniae infection. Trainees who received azithromycin were less likely than were trainees who received benzathine penicillin G to develop acute respiratory infection (risk ratio, 0.50; 95% confidence interval [CI], 0.28-0.92) and less likely at the end of training to report episodes of breathing difficulty (odds ratio [OR], 0.59; 95% CI, 0.34-1.01) or sore throat (OR, 0.66; 95% CI, 0.41-1.05). Compared with benzathine penicillin G prophylaxis, weekly oral azithromycin was superior in preventing respiratory infection in this population at transient high risk.     

Oral norfloxacin for prevention of gram-negative bacterial infections in patients with acute leukemia and granulocytopenia. A randomized, double-blind, placebo-controlled trial

We evaluated the effect of norfloxacin, 400 mg given orally every 12 hours, on the prevention of bacterial infections in 68 adult patients who had acute leukemia throughout prolonged courses of granulocytopenia (median, 32 days). Gram-negative infections were documented in 13 of the 33 patients receiving placebo, but only in 4 of the 35 patients receiving norfloxacin; no effect on the frequency of gram-positive or fungal infections was noted. Norfloxacin administration resulted in the suppression of gastrointestinal tract colonization by aerobic bacteria without the development of norfloxacin resistance. Patients receiving norfloxacin developed first infectious fevers later than did those receiving placebo, had more rapid resolution of that fever after systemic antibiotic treatment, and spent less time febrile. Therefore, although no difference was seen in survival duration, we found that the prophylactic administration of oral norfloxacin led to decreases in overall morbidity and gram-negative infections, was well tolerated, and did not predispose to the development of multiply drug-resistant bacteria.     

Randomized, double-blind, placebo-controlled trial of the immune modulator WF10 in patients with advanced AIDS

Summary  A randomized, double-blind trial compared treatment with the immune modulator WF10 (ten patients) and placebo (nine patients) administered in cycles over 3 months among individuals with advanced AIDS. There were no notable clinical adverse events; changes in hematologic and chemistry values were comparable in the two groups. In both groups, median HIV-RNA PCR values remained stable. Immunologic variables showed a consistent tendency to increase in the WF10 group and to decrease in the control group, with significant differences between groups for median WBC, lymphocyte, CD19, and CD35 values. Ten infections occurred in the control group, four of which werePneumocystis carinii pneumonia (PCP), and three in the WF10 group none of which was PCP. Five patients in the control group were hospitalized during the trial for a total of 53 days; no patients in the WF10 group were hospitalized. Over a subsequent 9-months follow-up, six patients from the control group and one from the WF10 group died. These results indicate that WF10 administration appears safe, may enhance immunologic function, and unlike other macrophage-activating cytokines does not increase HIV expression in this patient population. Further studies of WF10 in larger patient populations are warranted. Presented in part at the 7th International Congress for Infectious Diseases, 11 June 1996, Hong Kong.     

Randomized, prospective, double-blind, placebo-controlled trial of effect of nitroglycerin ointment on pain after hemorrhoidectomy

PURPOSE: Fissure-in-ano is characterized by pain, bleeding, and internal anal sphincter hypertonicity. Spasm of the internal sphincter also plays a role in hemorrhoidal disease and may be a source of anal pain after hemorrhoid surgery. Inducing sphincter relaxation with a nitroglycerin ointment has shown promise in healing anal fissures and relieving symptoms of pain. Our study attempts to test the hypothesis that topical nitroglycerin applied to the perianal region is beneficial in reducing pain after hemorrhoidectomy. METHODS: After hemorrhoidectomy 39 patients were randomly assigned to receive 0.2 percent nitroglycerin ointment (n=19) or placebo (n=20). Ointments were applied to the perianal region three times daily for seven days. Patients were prescribed hydrocodone bitartrate to take as needed. Visual analog scales were used to measure postoperative pain intensity and ointment benefits. Patients completed questionnaires to record medication morbidity and number of prescribed or nonprescribed medications taken. RESULTS: Patients using nitroglycerin had less pain and greater benefit from ointment than those did in the placebo group, but differences were not significant. Narcotic use was higher in the placebo group when considered on a daily basis, but was statistically significant on the second postoperative day only (P<0.05). Morbidity from ointment application was significantly higher in the nitroglycerin group (P<0.002) and included a headache in 8 of 19 patients. Nonsteroidal anti-inflammatory drugs and acetaminophen were not prescribed, but were taken more frequently in nitroglycerin patients (P<0.0003). CONCLUSION: Perianal application of 0.2 percent nitroglycerin ointment after hemorrhoidectomy significantly reduced narcotic requirements on the second postoperative day. Headaches and a subsequent need for nonnarcotic medications may limit benefits of nitroglycerin.Presented at the meeting of the American Society of Colon and Rectal Surgeons, Boston, Massachusetts, June 24 to 29, 2000.     

Schistosoma haematobium infections in two rural communities of Edo State, Nigeria

An epidemiological study of 1,136 inhabitants from two rural communities in Owan East local government area of Edo State, Nigeria was investigated to ascertain the prevalence, intensities and urinary symptoms in Schistosoma haematobium infections. In both communities, 371 (32.6%) of the villagers screened, excreted S. haematobium with a mean of 40.1 ova per 10 ml of their urine. The pattern of infection was highest among the school children, moderate among the farmers and least among the civil servants. The sensitivities of their urinary symptoms associated with this parasitic infection in these communities are 78.7% hematuria, 71.9% proteinuria, 70.4% supra public pain/discomforts and 59.6% dysuria. These foci of infections will broaden the epidemiological picture of urinary schistosomiasis in this part of the globe.