Flunarizine treatment in poor-grade aneurysm patients

Summary A cerebral Ca²⁺ overload blocker-flunarizine hydrochloride — was used with excellent results for prophylaxis of delayed ischaemic neurological deficit (DIND) in severe subarachnoid haemorrhage.The drug was administered orally at a dose of 10 mg, four times daily for four days, followed by three times daily for three days and twice daily for 14 more days.Of 72 patients treated with flunarizine, only one developed permanent DIND. 37 consecutive patients who were in Fisher's group III and were treated with flunarizine from immediately after early surgery were compared retrospectively with the 37 consecutive Control Group patients, who also belong to Fisher's group III. Among the Control Group patients, eight died from DIND and ten developed infarction from DIND, while flunarizine strongly prevented (p<0.001) DIND. Furthermore, the only one DIND was attributable to failure of administration of flunarizine.There were no side-effects from flunarizine.The association of severe angiographic vasospasm was less frequent in the Flunarizine Group (18% vs 57%, p<0.02).From this evidence, it might be concluded that flunarizine significantly inhibits the occurrence of severe neurological deficit due to delayed vasospasm. This highly beneficial effect on severe delayed vasospasm might be attributable to its intense inhibitory action on intracellular Ca²⁺ overloads especially in severe pathological situations.     

Improved treatment response with basiliximab immunoprophylaxis after liver transplantation: Results from a double-blind randomized placebo-controlled trial

Basiliximab, a high-affinity chimeric monoclonal antibody, is effective in reducing acute rejection episodes in renal allograft recipients. We assessed the ability of this antibody to similarly improve the outcome in liver transplant recipients. Adult recipients of a primary cadaveric liver transplant were randomized to treatment, stratified by hepatitis C virus (HCV) seropositivity. Patients were administered 40 mg of basiliximab (n = 188) or placebo (n = 193) as two 20-mg bolus injections days 0 and 4, plus cyclosporine and steroids. Primary efficacy variables were biopsy-confirmed acute rejection and its composite end point, including death or graft loss, and were assessed at 6 and 12 months and by HCV cohort. Because of differential efficacy responses between HCV-positive and HCV-negative cohorts, an additional analysis incorporating HCV recurrence as a component of treatment failure, termed problem-free transplant, was introduced. Safety and tolerability were monitored over the 12 months of the study. All 381 patients were assessable, and no meaningful differences in background characteristics were apparent between treatment groups. Biopsy-confirmed acute rejection rates 6 months after transplantation were 35.1% in the basiliximab group versus 43.5% in the placebo group. For death, graft loss, or first biopsy-confirmed acute rejection, rates were 44.1% versus 52.8%, respectively. The reduction in rejection episodes was concentrated in the HCV-negative cohort (14.5% relative to placebo; P = .034), with a much smaller difference (2.9%) in the HCV-positive cohort. For HCV-positive patients, problem-free transplant was shown at 12 months in 26.6% of the basiliximab group versus 11.6% in the placebo group (P = .020) and for all patients at 12 months in 39.7% of the basiliximab group versus 30.1% in the placebo group (P = .035). The incidence of infection and other adverse events was similar across the two treatment groups. There were 56 deaths (25 deaths, basiliximab group; 31 deaths, placebo group) over the 12-month study. The intravenous bolus injection was well tolerated. Immunoprophylaxis with 40 mg of basiliximab, in combination with cyclosporine and steroids, reduces the incidence of acute rejection episodes with no clinically relevant safety or tolerability concerns. The influence of HCV recurrence on efficacy results can be accounted for in future trials by using the concept of problem-free transplant, incorporating recurrence as a component of treatment failure. (Liver Transpl 2002;8:132-142.)     

Randomized placebo-controlled, double-blind trial of ketanserin in treatment of intermittent claudication.

Ketanserin, a selective serotonin (5-HT) antagonist at 5-HT2 receptors, was investigated in a 12-month, double-blind placebo-controlled study in 35 patients with intermittent claudication. Benefit was assessed by repeated treadmill tests, recording claudication distance, and by measurement of Doppler ankle-brachial pressure indices (ABPI) and pulse volume recordings (PVR). Improvement in claudication distance of 42-44% was noted during the 12 months of the double-blind study and this trend continued to 53-67% during an additional 3 month run-out period on placebo. There were no significant differences between the group given Ketanserin and the placebo group. The hemodynamic measurements demonstrated no statistically significant change in either ABPI or PVR throughout the study period, and no significant differences between the two groups. The conclusion of the study indicates that Ketanserin is ineffective in the treatment of intermittent claudication.     

Laparoscopic inguinal herniorrhaphy. Results of a multicenter trial.

OBJECTIVE: The purpose of this study was to determine if laparoscopic inguinal herniorrhaphy represents a viable alternative to the conventional repair and to assess whether a prospective randomized controlled trial comparing both procedures is warranted. METHODS: Three types of laparoscopic inguinal herniorrhaphies (transabdominal preperitoneal [TAPP], intraperitoneal onlay mesh [IPOM], and totally extraperitoneal [EXTRA]) were studied in a phase II design. Twenty-one investigators from 19 institutions participated. Approval from the local human research committee was required at each institution before patients could be enrolled. RESULTS: There were 686 patients with 869 hernias; 366 (42.1%) were direct, 414 (47.6%) were indirect, 22 (2.5%) were femoral, and 67 (7.7%) were combination hernias. The TAPP procedure was used for 562 hernias, the IPOM was used for 217 hernias, and the EXTRA was used for 87 hernias. Sixty-one patients had additional abdominal procedures performed at the time of laparoscopy without any adverse affects on their herniorrhaphies. The overall recurrence rate was 4.5%, with a minimum follow-up of 15 months. Complications were divided into the following three groups: 1) those related to laparoscopy, 2) those related to the patient, and 3) those related to the herniorrhaphy. Complications related to the laparoscopy occurred in 5.4% of patients; bleeding or abdominal wall hematomas occurred 31 times, (two patients required transfusion); one patient had bowel perforation, which was sutured laparoscopically; a bladder injury required laparotomy for management. Patient complications occurred in 6.7%. The majority involved the urinary tract (5.8%). Two patients required secondary abdominal procedures for adhesions, one for pain in the right lower quadrant and the other for adhesive small bowel obstruction. Postoperative myocardial infarction on day 5 resulted in the only operative mortality, for a rate of 0.1%. Complications related to the herniorrhaphy itself occurred in 17.1%. Most of these were minor, consisting of transient groin pain (3.5%), seroma (3.5%), transient leg pain (3.3%), hematoma (1.5%), or transient cord or testicular problems (0.9%). The incidence of leg pain decreased dramatically as surgeons became more familiar with the anatomy of the nerve supply to the groin when viewed laparoscopically. Ninety-three percent of patients were discharged within 24 hours of their operations. CONCLUSIONS: Laparoscopic inguinal herniorrhaphy is an effective method to correct an inguinal hernia. It can be offered safely to patients undergoing other abdominal procedures. The TAPP, IPOM, and EXTRA procedures appear to be equally effective. A controlled randomized trial is needed to compare this procedure with conventional inguinal herniorrhaphy.     

Results of early surgical evacuation of packed intraventricular hemorrhage from aneurysm rupture in patients with poor-grade subarachnoid hemorrhage.

OBJECT: The goal of this study was to evaluate the results of early surgical evacuation of "packed" intraventricular hemorrhage (IVH) in patients with poor-grade subarachnoid hemorrhage (SAH). METHODS: The authors performed surgery within 24 hours after onset of SAH, identified on neuroimaging as a cast distending the ventricular system, in 74 patients with poor-grade SAH (World Federation of Neurosurgical Societies Grades IV and V) without intracerebral hemorrhage. Eighteen of these patients had packed IVH; in these patients the intraventricular clots were extensively evacuated via frontal corticotomy performed under microscopic view. CONCLUSIONS: Overall, 42% of the 74 patients undergoing craniotomy in the acute stage had favorable outcomes, whereas 30% died. Using multivariate analysis, variables significantly associated with favorable outcome in patients with poor-grade SAH included absence of a packed intraventricular clot on computerized tomography scanning; absence of a history of cardiac disease; and a Glasgow Coma Scale score of 11 or 12. None of the 18 patients who had packed IVH had favorable outcomes and seven of these died. In six recently treated patients with packed IVH, which was examined using fluid-attenuated inversion recovery imaging, extensive periventricular brain damage was found both immediately after surgery and during the chronic stage. Accordingly, the authors believe that irreversible periventricular brain damage is already complete immediately after packed IVH occurs.     

Gabapentin therapy for pruritus in haemodialysis patients: a randomized, placebo-controlled, double-blind trial.

BACKGROUND: Uraemic pruritus is a common and distressing symptom in patients on haemodialysis for chronic renal failure. Gabapentin is an anticonvulsant that alleviates neuropathic pain. We conducted a double-blind, placebo-controlled, crossover study to assess its effectiveness against renal itch. METHODS: We enrolled in the trial 25 adult patients on haemodialysis who were asked to daily record the severity of their pruritus on a visual analogue scale. The patients were randomly assigned to receive gabapentin for 4 weeks followed by placebo for 4 weeks or the reverse sequence. Gabapentin or placebo were administered thrice weekly, at the end of haemodialysis sessions. RESULTS: The mean pruritus score of the cohort before the study was 8.4 +/- 0.94. After placebo intake, it decreased to 7.6 +/- 2.6 (P = 0.098). The score of four patients decreased by >50% following placebo. After gabapentin administration, the mean score decreased significantly, to 1.2 +/- 1.8 (P = 0.0001), although one patient's symptoms did not improve significantly. No patient dropped out of the study due to adverse effects from gabapentin. CONCLUSIONS: Our study shows that gabapentin is safe and effective for treating uraemic pruritus in haemodialysis patients. Our results also support the neuropathic hypothesis of uraemic pruritus.     

Management morbidity and mortality of poor-grade aneurysm patients

Preliminary experience with the occasional good survival of patients in Hunt and Hess Grade IV or V with aneurysmal subarachnoid hemorrhage (SAH) led to a prospective management protocol employed during a 2 1/2-year period. The protocol utilized computerized tomography (CT) scanning to diagnose SAH and to obtain evidence for irreversible brain destruction, consisting of massive cerebral infarction with midline shift or dominant basal ganglia or brain-stem hematoma. These patients, along with those who exhibited poor or absent intracranial filling on CT or angiography, were excluded from active treatment and given supportive care only. All other patients had immediate ventriculostomy placement and, if intracranial pressure (ICP) was controllable (less than or equal to 30 cm H2O without an intracranial clot or less than or equal to 50 cm H2O in the presence of a clot), went on to have craniotomy for aneurysm clipping. Aggressive postoperative hypertensive, hypervolemic, hemodilutional therapy was subsequently employed. Of 54 patients with poor-grade aneurysms, ventriculostomy was placed in 47 (87.0%) and yielded high ICP's in the overwhelming majority, with the mean ICP being 40.2 cm H2O. Nineteen poor-grade aneurysm patients received no surgical treatment and survived a mean of 31.8 hours with 100% mortality. Thirty-five patients underwent placement of a ventriculostomy, craniotomy for aneurysm clipping and intracranial clot evacuation, and postoperative hypertensive, hypervolemic, hemodilutional therapy. The outcome at 3 months of the 35 patients who were selected for active treatment was good in 19 (54.3%), fair in four (11.4%), poor in four (11.4%), and death in eight (22.9%). It is concluded that poor-grade aneurysm patients usually present with intracranial hypertension, even those without an intracranial clot. Based on radiographic rather than neurological criteria, a portion of these patients can be selected for active and successful treatment. Increased ICP can be present without ventriculomegaly, and immediate ventriculostomy should be performed. As long as ICP is controllable, craniotomy and postoperative intensive care can effect a favorable outcome in a significant percentage of these patients.     

Biological effects of acute pravastatin treatment in patients after aneurysmal subarachnoid hemorrhage: a double-blind, placebo-controlled trial

OBJECT: The authors previously demonstrated that acute pravastatin therapy in patients after aneurysmal subarachnoid hemorrhage (SAH) ameliorates vasospasm-related delayed ischemic neurological deficits. The object of this study was to continue to examine potential mechanisms of these beneficial effects. METHODS: Eighty patients with aneurysmal SAH (age range 18-84 years; time to onset 1.8 +/- 1.3 days) were enrolled in a double-blind study and randomized to receive 40 mg of oral pravastatin or placebo daily for as long as 14 days. Daily transcranial Doppler ultrasonography and blood tests every 3 days (including full blood cell counts, coagulation profiles, fasting glucose and lipid profiles, and serum biochemistry) were performed during the trial period. RESULTS. No significant differences were found in baseline laboratory data between the trial groups. Subsequent measurements during the 14-day trial showed reduced low-density lipoprotein (LDL) cholesterol levels and total/high-density lipoprotein cholesterol ratios between Days 3 and 15 (p < 0.05), and increased D-dimer levels (p < 0.05) on Day 6, in the pravastatin group. Patients who received pravastatin but developed vasospasm had significantly lower baseline LDL cholesterol levels or a less extensive reduction in LDL cholesterol levels (p < 0.05), and greater increases in plasma fibrinogen (p = 0.009) and serum C-reactive protein on Day 3 (p = 0.007), compared with those patients without vasospasm. The reduction in LDL cholesterol levels on Day 3 in the placebo group correlated with the duration of normal cerebral autoregulation on the ipsilateral side of the ruptured aneurysm (p = 0.002). CONCLUSIONS. In addition to functioning through a cholesterol-independent pathway, cerebrovascular protection from acute statin therapy following aneurysmal SAH may also function through cholesterol-dependent mechanisms.     

Effect of AT877 on cerebral vasospasm after aneurysmal subarachnoid hemorrhage. Results of a prospective placebo-controlled double-blind trial.

With the cooperation of 60 neurosurgical centers in Japan, a prospective randomized placebo-controlled double-blind trial of a new calcium antagonist AT877 (hexahydro-1-(5-isoquinolinesulfonyl)-1H-1,4-diazepine hydrochloride, or fasudil hydrochloride) was undertaken to determine the drug's effect on delayed cerebral vasospasm in patients with a ruptured cerebral aneurysm. A total of 276 patients, who underwent surgery within 3 days after subarachnoid hemorrhage (SAH) of Hunt and Hess Grades I to IV, were entered into the study. Nine patients were excluded because of protocol violation. The remaining 267 patients received either 30 mg AT877 or a placebo (saline) by intravenous injection over 30 minutes, three times a day for 14 days following surgery. Demographic and clinical data were well matched between the two groups. It was found that AT877 reduced angiographically demonstrable vasospasm by 38% (from 61% in the placebo group to 38% in the AT877 group, p = 0.0023), low-density regions on computerized tomography associated with vasospasm by 58% (from 38% to 16%, p = 0.0013), and symptomatic vasospasm by 30% (from 50% to 35%, p = 0.0247). Furthermore, AT877 reduced the number of patients with a poor clinical outcome associated with vasospasm (moderate disability or worse on the Glasgow Outcome Scale at 1 month after SAH) by 54% (from 26% to 12%, p = 0.0152). There were no serious adverse events reported in the AT877 group. This is the first report of a placebo-controlled double-blind trial that has demonstrated a significant reduction in angiographically revealed vasospasm by intravenous drug therapy.     

Prophylactic isradipine treatment after kidney transpIantation: a prospective double-blind placebo-controlled randomized trial

Abstract There is evidence that calcium antagonists may have a beneficial effect on cyclosporineinduced nephropathy after transplantation. We treated 50 consecutive non-diabetic patients receiving their first cadaveric transplant with isradipine, a dihydropyridine calcium antagonist, or placebo in a double-blind, randomized, placebocontrolled trial. There were no significant differences between the two groups as regards age, weight, sex, HLA matching and ischaemic periods. To achieve optimal vasodilation, treatment was started intravenously 2 h before the transplantation procedure, and continued orally afterwards for 3 months. The immunosuppressive treatment included rabbit antithymocyte globulin on day 0, and oral cyclosporine from day 5. In both groups 7 patients had primary non-functioning grafts, but the incidence of never functioning kidneys due to vascular and thrombotic complications was significantly higher in the placebo group (0 vs 4 patients, P < 0.05). Hypertension was treated with oral labetolol in combination with guanfacine if necessary. In the placebo group antihypertensive medication had to be prescribed significantly more often (67% vs 33% of patients, P < 0.05), but resulted in similar blood pressure recordings in the two study groups. Cyclosporin A (CsA) plasma concentrations were also comparable but in the isradipine group a significantly higher dose of CsA was needed to achieve adequate levels (8.0 ± 0.5 vs 6.2 ± 0.5 mg/kg per day, P < 0.01). However, in the isradipine-treated patients creatinine clearance was significantly higher (66.1 ± 4.5 vs 55.6 ± 6.2 ml/min, P < 0.05) after 3 months. We conclude that isradipine is an effective antihypertensive agent after kidney transplantation. Isradipine ameliorates CsA-induced nephropathy and seems to protect against early postoperative vascular complications.     

One-stage embolization in patients with acutely ruptured poor-grade aneurysm

BACKGROUND: Early or ultra-early surgery for patients in poor neurological condition (Hunt and Hess grade IV or V) after ictus of aneurysmal subarachnoid hemorrhage is increasingly reported to prevent early rebleeding. To prevent any rebleeding after hospital admission, we have treated patients with poor-grade aneurysm during the same session as when diagnostic angiography is performed ("one-stage embolization"). The aim of the present study is to determine whether this treatment modality is a viable management option for this group of patients. METHODS: We retrospectively reviewed 18 consecutive patients who presented with acutely ruptured aneurysms and were in very poor neurological condition and who were treated with one-stage embolization. RESULTS: We observed 2 complications related to the endovascular procedure: partial occlusion of the parent artery and aneurysm rupture during the procedure. According to the Glasgow Outcome Scale, good recovery occurred in 8 patients, and moderate and severe disabilities occurred in 4 and 3 patients, respectively, and 3 patients died. No rebleeding occurred after the procedure. The mean follow-up of the surviving patients (those who were alive more than 30 days after embolization) was 13.7 months (4-25 months). Three patients had surgery after endovascular procedure: 2 surgical clipping of failed or partial aneurysm embolization and 1 emergency coil removal with clipping. A permanent ventriculoperitoneal shunt was placed in 11 patients. CONCLUSIONS: We achieved promising results by using one-stage embolization to prevent ultra-early rebleeding followed by aggressive resuscitation. The active involvement of the endovascular team from the stage of diagnostic angiogram is a prerequisite for this treatment strategy.     

Anti-endotoxin in the treatment of severe surgical septic shock. Results of a randomized double-blind trial

A randomized double-blind trial of human antilipopolysaccharide (anti-LPS)-specific globulin (LG-1) versus placebo (albumin) in the treatment of severe septic shock of surgical origin was carried out over a 6-month period from June to December 1983. Hospital mortality was 10 patients (59%) out of 17 in the control group and 9 out of 17 (53%) in the treated group. Irreversible shock was the cause of death in 4 patients (23,5%) in the control group and 5 (29,4%) in the treated group. Duration of hospital stay of the survivors averaged 44 days for the control group and 62 for the treated group. Measurement of serum endotoxin and anti-LPS levels at the time of admission to the study and 24 hours later revealed no significant difference between controls and treated patients. Significantly higher mortality rates were observed in patients who were endotoxemic after 24 hours of treatment compared with those who were not (chi 2 = 4,80; P less than 0,025).     

Adjuvant treatment of knee osteoarthritis with weak pulsing magnetic fields. Results of a placebo-controlled trial prospective clinical trial

PURPOSE: The aim of this study was the objective control of the therapeutic effect of weak pulsing magnetic fields (series of periodically repeating square pulses increasing according to an e-function, frequencies of 10, 20, 30, and 200-300 Hz) by means of a double-blind study on osteoarthritis of the knee. Measured parameters were the Knee Society score, pain sensation, blood count and cardiocirculatory values. METHODS: 36 placebo and 35 verum test persons (all with a knee gap smaller than 3 mm) were exposed daily for 16 minutes over 6 weeks to a low frequency magnetic field (flux densities increasing gradually from 3.4 up to 13.6 microT) encompassing the whole body. The last data collection was made 4 weeks after the end of treatment. RESULTS: Principally, the statistically ensured results exclusively favour the used magnetic field therapy; by far the greatest number of at least significant differences was found at the end of the whole treatment, lasting 6 weeks. In particular, it is striking that all 4 questioned pain scales showed at least significant improvements in favour of the verum collective; also the walking distance was increased. As another confirmed fact, even after 4 weeks without therapy the persistence of several functional and analgesic effects could be documented. CONCLUSIONS: Predominantly, on the one hand, pain relief in osteoarthritis patients was confirmed by a double-blind trial, on the other hand, increases in mobility could be proven. Furthermore, we describe mainly the modes of action of low frequency magnetic energy and 3 physical concepts that are seen as the connecting link between electromagnetic fields coupled into connective tissue and biochemical repair and growth processes in bones and cartilage. Proceeding from the results of this and preceding studies, one has to consider seriously whether this kind of magnetic field application should not be employed as cost-effective and side effect-free alternative or adjuvant form of therapy in the field of orthopaedic disorders.     

Efficacy of repeat intravenous dosing of ondansetron in controlling postoperative nausea and vomiting: a randomized, double-blind, placebo-controlled multicenter trial.

STUDY OBJECTIVES: To compare repeat intravenous (i.v.) dosing of ondansetron 4 mg with placebo for the treatment of postoperative nausea and vomiting (PONV) in patients for whom prophylactic, preoperative ondansetron 4 mg i.v. was inadequate DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Ten outpatient surgical centers in the United States. PATIENTS: 2,199 male and female ASA physical status I, II, and III patients > or = 12 years old scheduled to undergo outpatient surgical procedures and receive nitrous oxide-based general anesthesia. INTERVENTIONS: Ondansetron 4 mg i.v. was administered to all patients before induction of general anesthesia. Patients who experienced PONV or requested antiemetic therapy within 2 hours after discontinuation of inhaled anesthesia were randomized (1:1) to either a repeat i.v. ondansetron 4 mg dose or placebo. MEASUREMENTS AND MAIN RESULTS: Of the 2,199 patients prophylactically treated with ondansetron 4 mg before anesthesia induction, 1,771 (80.5%) did not experience PONV or request antiemetic therapy during the 2 hours following discontinuation of anesthesia. Of the 428 patients who experienced PONV or requested antiemetic therapy during the same period, and were randomized to additional treatment (214 randomized to ondansetron, 214 randomized to placebo), the incidence of complete response (no emesis, no rescue medication, no study withdrawal) was similar for both ondansetron-randomized and placebo-randomized groups for the 2-hour (34% and 43%, respectively, p = 0.074) and 24-hour (28% and 32%, respectively, p = 0.342) postrandomization study periods. Repeat ondansetron dosing was not more effective than placebo in controlling either postoperative emesis or the severity/duration of postoperative nausea. The administration of an additional dose of ondansetron 4 mg postoperatively did not result in an increased incidence of adverse effects. CONCLUSIONS: In patients for whom preoperative prophylaxis with ondansetron 4 mg i.v. is not successful, a repeat dose of ondansetron 4 mg i.v. in the postanesthesia care unit does not appear to offer additional control of PONV.     

Safety and hemostatic effect of recombinant activated factor VII in cirrhotic patients undergoing partial hepatectomy: a multicenter, randomized, double-blind, placebo-controlled trial

BACKGROUND: Coagulopathy caused by cirrhosis may contribute to excessive bleeding during hepatectomy. We evaluated the hemostatic effect and safety of recombinant factor VIIa (rFVIIa) in cirrhotic patients undergoing partial hepatectomy. METHODS: Patients were randomized to rFVIIa 50 or 100 mug/kg or placebo, administered intravenously 10 minutes before surgery and every second hour during surgery. The primary efficacy end points were the proportion of patients receiving red blood cell (RBC) transfusions and the amount of RBCs transfused. The RBC transfusion trigger was blood loss of 500 mL. Safety end points included thromboembolic and adverse events. RESULTS: No statistically significant effect of rFVIIa treatment on efficacy end points was observed. Serious and thromboembolic adverse events occurred at similar incidences in the study groups. CONCLUSIONS: Using blood loss as a transfusion trigger, the efficacy of rFVIIa in reducing the requirement for RBC transfusion was not established in this study. No safety concerns were identified.     

Efficacy and safety of once-daily dosing of udenafil in the treatment of erectile dysfunction: results of a multicenter, randomized, double-blind, placebo-controlled trial

Background

A once-daily dosing regimen with a phosphodiesterase type 5 inhibitor is needed for the treatment of erectile dysfunction (ED), in part because of the behavioral complexities associated with sexual intimacy. Many patients prefer spontaneous rather than scheduled sexual activities or they anticipate frequent sexual encounters. The pharmacokinetic profiles of udenafil with a time of maximal concentration of 1.0-1.5 h and a terminal half-life of 11-13 h make udenafil a good candidate for once-daily dosing.

Objective

To evaluate the efficacy and safety of once-daily dosing of udenafil in the treatment of ED.

Design, setting, and participants

This multicenter randomized double-blind, placebo-controlled, fix-dosed clinical trial involved 237 patients with ED. The subjects, who were treated with placebo or udenafil (25 mg, 50 mg, or 75 mg) once daily for 12 wk, were asked to complete the International Index of Erectile Function (IIEF), the Sexual Encounter Profile (SEP) diary, and the Global Assessment Questionnaire (GAQ) during the study.

Measurements

The primary outcome parameter was the change from baseline for the IIEF erectile function domain (EFD) score. The secondary outcome parameters were SEP questions 2 and 3, the shift to normal rate (EFD ≥26), and the response to the GAQ.

Results and limitations

Compared with placebo, patients who took 50 mg or 75 mg of udenafil had a significantly improved IIEF-EFD score. Similar results were observed in comparing questions 2 and 3 in the SEP diary and the GAQ. Flushing was the most common treatment-related adverse event, which was transient and mild to moderate in severity.

Conclusions

Udenafil significantly improved erectile function among ED patients when administered in doses of 50 mg or 75 mg once daily for 12 wk. Daily administration of udenafil (50 mg) may be another treatment option for ED.