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PubMed1986

Overall safety of terazosin as an antihypertensive agent.

The safety of terazosin, an effective agent for the treatment of hypertension, was assessed by analyzing data from 1,006 hypertensive patients who were enrolled in short-term and/or long-term studies. The total experience with terazosin in this article represents 422.5 patient-years. Changes in pulse rate measurements from pretreatment to posttreatment were not significantly different between the terazosin- and placebo-treated patients (-1.0 beat per minute for the terazosin group and -1.0 beat per minute for the placebo group, in the supine position). Dizziness, headache, and asthenia were the most commonly reported adverse experiences among all terazosin-treated patients, although the incidence of headache in placebo-controlled trials was not significantly different between the terazosin and placebo groups. As a whole, patients receiving terazosin had a tendency to gain small amounts of weight (2 pounds). In addition, there was a trend for slight decreases in hemoglobin, hematocrit, white blood cell count, total protein, and albumin levels in those patients who received terazosin, suggesting hemodilution. Overall, terazosin was shown to be safe in patients with mild to moderate essential hypertension.

Adolescent↗
PubMedDate not supplied

Androgens and aging in men.

Androgen levels decrease with aging in men. Androgen deficiency in elderly men may lead to asthenia, decrease in muscle mass, osteoporosis, decrease in sexual activity, and, in some cases, changes in mood and cognitive function. Combination of these factors may result in impaired quality of life in the elderly male. Androgen replacement therapy may increase bone and muscle mass, enhance muscle and cardiovascular function, and improve sexual function and general well-being. These potential benefits of androgens have to be weighed against the possible adverse effects on prostate and cardiovascular diseases. Careful long-term studies will be required to assess the risk-to-reward ratios of androgen or other hormone replacement therapy before the development of treatment strategies similar to estrogen and progestagen substitution therapy for the postmenopausal female.

Aged↗
PubMed1993

A dose-response study of clentiazem, a chloro-derivative of diltiazem, in patients with stable angina. CAMCAT Study Group.

OBJECTIVES: The efficacy and safety of clentiazem were assessed in 199 patients with stable angina in a dose-ranging, placebo-controlled, double-blind, parallel design study. BACKGROUND: To date, this is the first large efficacy and safety study of clentiazem in patients with stable angina. METHODS: After washout and a 1-week placebo run-in period, patients received 20, 40, 80 or 120 mg/day of clentiazem tablets or placebo as a twice-daily dosage for 1 week of treatment after 1 week of dose titration. A symptom-limited exercise tolerance test was performed 4 and 12 h after dosing at the end of treatment and results were compared with baseline measurements. RESULTS: At 4 h after dosing, improvement of exercise duration from baseline value was significantly greater with clentiazem at doses of 40 mg/day (63 +/- 11 s), 80 mg/day (99 +/- 10 s) and 120 mg/day (70 +/- 11 s) than with placebo (34 +/- 10 s). Moreover, clentiazem (80 and 120 mg/day) increased the time to onset of angina and to > or = 1 mm of ST segment depression significantly more than did placebo. At submaximal exercise, clentiazem (40, 80 and 120 mg/day) decreased rate-pressure product, mainly as a result of a decrease in heart rate. At 12 h after dosing, improvement of exercise duration from baseline was significantly greater with clentiazem in doses of 80 mg/day (77 +/- 9 s) and 120 mg/day (70 +/- 10 s) than with placebo (42 +/- 9 s). The incidence of treatment-related adverse events with placebo (27%) and clentiazem (29%) was similar. The most frequently reported treatment-related adverse events with clentiazem were asthenia, headache (both 7.9%), first-degree atrioventricular block and dizziness (both 4.4%). CONCLUSIONS: The results of this short-term study suggest that clentiazem given twice daily in doses of 80 or 120 mg/day is safe and effective monotherapy in the treatment of stable angina.

Aged↗
PubMed1994

Proximal muscle weakness in a patient with hepatocellular carcinoma.

Asthenia and generalized weakness are common in cancer patients. There are multiple causes for these symptoms. We describe a case of rapid onset of proximal muscle weakness in a patient with hepatocellular carcinoma. The differential diagnosis of muscle weakness in the palliative care patient is reviewed. The discussion centers on steroid myopathy and its treatment.

Asthenia↗
PubMed2005

Food-cobalamin malabsorption in elderly patients: clinical manifestations and treatment.

PURPOSE: Approximately 15% of people aged more than 60 years old have a cobalamin (vitamin B12) deficiency, mainly in relation with food-cobalamin malabsorption (FCM). To date, no study has documented this disorder in the elderly. There is also little information on clinical consequences. SUBJECTS AND METHODS: We studied 92 elderly patients with well-established FCM who were extracted from an observational cohort study (1995-2004) of 172 consecutive elderly patients with documented cobalamin deficiency. RESULTS: The median patient age was 76 +/- 8 years; 60 patients were women. The most common clinical manifestations were neurologic or psychologic: mild sensory polyneuropathy (44.6%), confusion or impaired mental functioning (22.8%), and physical asthenia (20.7%). Hematologic abnormalities were reported in at least one third of the patients: anemia (21%), leukopenia (10.9%), thrombopenia (8.7%), and pancytopenia (6.5%). All patients had low serum vitamin B12 levels (<200 pg/mL), with a mean value (+/- standard deviation) of 131 +/- 38 pg/mL and total serum homocysteine level of 22.1 +/- 9.3 micromol/L. The mean hemoglobin level was 10.9 +/- 2.5 g/dL and the mean erythrocyte cell volume 95.7 +/- 12.7 fL. Correction of the serum vitamin B12 levels and hematologic abnormalities was achieved equally well in patients treated with either intramuscular or oral crystalline cyanocobalamin. CONCLUSIONS: This study suggests that in elderly patients, FCM may be associated with significant neurologic, psychologic, and hematologic abnormalities, which seem to respond equally well to either oral or parenteral vitamin B12 therapy.

Aged↗
PubMed2004

Monocyte cytokine secretion in patients with pulmonary tuberculosis differs from that of healthy infected subjects and correlates with clinical manifestations.

Cell-mediated immunity, leading to Mycobacterium tuberculosis (Mtb)-constraining granuloma formation, is the major component of host defense against tuberculosis and is regulated by the balance of cytokines secreted mostly by mononuclear phagocytes and lymphocytes. To better understand the role of monocytes in the regulation of the immune response against pulmonary tuberculosis, we examined IL-10, IL-12 and TNF-alpha release by monocytes from healthy purified protein derivative (PPD) reactors and pulmonary tuberculosis patients with or without systemic reactions (e.g., fever, weight loss, asthenia). Our study shows that, probably as a result of in vivo priming by circulating antigens, monocytes from patients, especially those with systemic manifestations, have a biased ex vivo cytokine secretion, with high IL-10 and TNF-alpha but low IL-12, in contrast with PPD reactors. Higher spontaneous IL-10 and TNF-alpha release persisted when monocytes were co-cultured with autologous lymphocytes. Challenge of patients' monocytes with a virulent Mtb strain led to a further enhancement of IL-10 and TNF-alpha, but not of IL-12. When lymphocytes were added to these cultures, IL-10 and TNF-alpha elevation persisted and, in the patients with a systemic reaction, both IL-12 and IFN-gamma were significantly reduced compared to PPD reactors. Intragroup comparisons revealed that in the patients with systemic reactions, the lymphocyte-monocyte interaction resulted in a positive feedback for IL-10 secretion, while in the patients without systemic reaction and PPD reactors, the feedback was positive for IL-12 secretion. Thus, in tuberculosis, there appears to exist a relationship between the immunological findings and the distinct clinical manifestations.

Adolescent↗
PubMed2002

[Etiologic spectrum of solitary constitutional syndrome].

OBJECTIVE: To know the spectrum of diseases responsible for the solitary constitutional syndrome in our setting. This syndrome was defined as a clinical picture characterized by the presence of asthenia, anorexia, and weight loss of at least 5% of body weight in the last six months, not associated with any other symptom or sign suggesting the diagnosis of an organ or system disease. PATIENTS AND METHODS: All patients diagnosed of the solitary constitutional syndrome (328) in a tertiary-care level teaching hospital between January 1991 and December 1996. RESULTS: Fifty-two (170) percent of patients with solitary constitutional syndrome were males and 48% (158) females. The mean age was 65.4%, ranging from 15 to 97 years. The average of the monthly estimated weight loss was 3 to 4 kilograms. A total of 115 (35%) malignant neoplasms and 5 (1.5%) benign tumors were diagnosed. The most common malignant tumors corresponded to the digestive tract (51.3% of the total malignant tumors). The second cause in frequency of the solitary constitutional syndrome corresponded to psychiatric diseases, with a total of 80 patients (24.3%). A total of 116 non-neoplastic organic diseases were detected, with digestive tract diseases --mainly peptic disease-- being the most common cause in this group. After follow-up, only in twenty cases were we unable to detect the underlying disease responsible for the syndrome. In nine of these, the solitary constitutional syndrome was self-limited. Forty-four percent of patients had at least another concomitant disease and in 24% of patients more than one associated condition was found. CONCLUSION: The most common diseases responsible for the solitary constitutional syndrome were, by decreasing frequency, malignant tumors, psychiatric disorders, and non-malignant organic diseases located in the digestive tract. A better knowledge of the etiological spectrum of this syndrome might be useful for a more efficient management of these patients.

Adolescent↗
PubMed1987

Ketoconazole therapy for advanced prostatic cancer: feasibility and treatment results.

To investigate the feasibility and antitumoral effect of ketoconazole in the treatment of disseminated prostatic cancer, 22 patients with stage D2 disease were treated with 400 mg. ketoconazole orally every 8 hours. Of the 17 patients evaluable for antitumoral effect an initial tumor response of 88 per cent was observed (1 complete and 8 partial responses, and 6 with stable disease) with a mean duration of 15.8 months (range 5 to more than 30 months). Treatment-related side effects were encountered in 21 patients and consisted of asthenia, gastrointestinal complaints, skin reactions and cardiovascular complications. They were judged to be mild in 8 patients, moderate in 5 and severe in 8. Treatment had to be discontinued because of side effects in 7 patients (32 per cent). During treatment with ketoconazole serum testosterone levels decreased rapidly and attained nearly castrate levels at the end of week 3. However, after 1 month a steady increase was noted and the testosterone levels reached low normal ranges after 5 months. No hormonal or biochemical indications of adrenocortical insufficiency were noted. High dose ketoconazole is effective in the treatment of disseminated prostatic cancer. Its use is limited by the side effects and the inability to maintain castrate levels of testosterone.

Adenocarcinoma↗
PubMed1998

Macrophagic myofasciitis: an emerging entity. Groupe d'Etudes et Recherche sur les Maladies Musculaires Acquises et Dysimmunitaires (GERMMAD) de l'Association Française contre les Myopathies (AFM).

BACKGROUND: An unusual inflammatory myopathy characterised by an infiltration of non-epithelioid histiocytic cells has been recorded with increasing frequency in the past 5 years in France. We reassessed some of these cases. METHODS: We did a retrospective analysis of 18 such cases seen in five myopathology centres between May, 1993, and December, 1997. The myopathological changes were reassessed at a clinopathology seminar. FINDINGS: Detailed clinical information was available for 14 patients. The main presumptive diagnoses were polymyositis and polymyalgia rheumatica. Symptoms included myalgias in 12 patients, arthralgias in nine, muscle weakness in six, pronounced asthenia in five, and fever in four. Abnormal laboratory findings were occasionally observed, and included raised creatine kinase concentrations, increased erythrocyte sedimentation rate, and myopathic electromyography. Muscle biopsy showed infiltration of the subcutaneous tissue, epimysium, perimysium, and perifascicular endomysium by sheets of large macrophages, with a finely granular PAS-positive content. Also present were occasional CD8 T cells, and inconspicuous muscle-fibre damage. Epithelioid and giant cells, necrosis, and mitotic figures were not seen. The images were easily distinguishable from sarcoid myopathy and fasciitis-panniculitis syndromes. Whipple's disease, Mycobacterium avium intracellulare infection, and malakoplakia could not be confirmed. Ten patients were treated with various combinations of steroids and antibiotics; symptoms improved in eight patients, and stabilised in two. INTERPRETATION: A new inflammatory muscle disorder of unknown cause, characterised by a distinctive pathological pattern of macrophagic myofasciitis, is emerging in France.

Adult↗
PubMed2002

Phase II study of paclitaxel (Genaxol) and cisplatin combination in treating Chinese patients with advanced non-small cell lung cancer (NSCLC).

PURPOSE: To assess the efficacy of 3-h paclitaxel infusion (Genaxol) combined with cisplatin as the first line chemotherapy for patients with advanced/metastatic non-small cell lung cancer (NSCLC). The aim of the present study is to evaluate the efficacy, safety, and quality of life of the combination of paclitaxel (Genaxol) and cisplatin on Chinese patients. METHODS: Forty-five patients with histology confirmed NSCLC, who met the selection criteria were enrolled in this study between June 1999 and May 2000. They were all at an advanced stage, i.e. stage IIIB with pleural effusion, or stage IV. Paclitaxel (Genaxol) at a dose of 175 mg/m(2) and cisplatin at a dose of 75 mg/m(2) were administered every 3 weeks. RESULTS: Of the 45 eligible patients, one had a CR and 19 achieved a PR. The overall response was 44.4% (95% CI: 29.3-59.5%). Eleven (24.4%) patients were in stable disease. The median time to disease progression for all patients was 5.5 months (95% CI: 4.0-7.0 months). The median survival was 11.1 months (95% CI: 6.6-15.6 months), the 1-year survival probability was 46.5%. Major non-hematology toxicities were asthenia, paresthesias, nausea, and vomiting. Hematological toxicity results showed 18 (40%) patients experienced grade 3/4 neutropenia but there was no febrile neutropenia, three (6.6%) patients experienced Grade 3 anemia, and one (2.2%) patient experienced Grade 3 thrombocytopenia. CONCLUSIONS: The combined paclitaxel and cisplatin regimen is safe and effective in the treatment of NSCLC but the quality of life is disappointed.

Adult↗
PubMed2006

Primary human immunodeficiency virus type 1 infection: clinical, virological and immunological characteristics of 75 patients (1997-2003).

OBJECTIVES: To describe the epidemiological and clinical characteristics and the evolution of a cohort of patients with primary HIV-1 infection from the Barcelona area. METHODS: Prospective cohort study of HIV-infected patients diagnosed with primary HIV infection in a tertiary hospital in Barcelona (Spain) from 1997 through 2003. Descriptive analysis of epidemiological and clinical characteristics and effect of highly active antiretroviral treatment (HAART) on outcome. RESULTS: A total of 75 patients were diagnosed, accounting for 2.9% of the total of newly diagnosed HIV patients during the same time period. Eighty-one percent of the patients were males and the median age was 30 years (IQR 26-38). The most frequent transmission route was homosexual (72%), followed by heterosexual (17%) and intravenous drug abuse (11%). Seventy-seven percent of patients presented symptoms, the most frequent being fever (98%), asthenia (86%), arthralgia-myalgia (65%), lymphadenopathy (55%), night sweats (48%) and rash. Sixty-five percent started HAART, although the proportion of patients that received HAART decreased from 79% during the period 1997-2000 to 49% during the period 2001-2003 (p < 0.01). After a median follow-up of 37 months (IQR 26-66), one patient died and eight cases were lost to follow-up. The patients who did not receive HAART had a higher probability of immunological or clinical deterioration during the follow-up when compared to the group that received HAART (42.3% versus 12.3%; p < 0.001). In treated patients, dyslipidemia and lipodystrophy were diagnosed in 58% and 37% of cases, respectively. CONCLUSIONS: Primary HIV-1 infection was diagnosed more frequently in homosexual males, and its clinical characteristics were similar to those observed in previous studies. HAART given during primary HIV infection was effective, but was associated with a high percentage of adverse effects.

Adult↗
PubMed2003

[Vitamin B12 deficiency with normal Schilling test or non-dissociation of vitamin B12 and its carrier proteins in elderly patients. A study of 60 patients].

PURPOSE: Approximately 15% of people over 60 years old have a cobalamin (Cbl) deficiency in relation with a food-cobalamin malabsorption (FCM). But to date, only case reports or small series have been reported. The aim of this study was to describe the clinical characteristics of the FCM in old subjects. METHODS: Sixty patients, at least 65 years old, presenting a Cbl deficiency related to FCM, were extracted from a cohort study of the Hôpitaux universitaires de Strasbourg, France (n = 169). All these patients had an established diagnosis of Cbl deficiency and met the Carmel's criteria of FCM. Their clinical data were retrospectively analysed. RESULTS: The median age of the 60 patients was 75 years and the female/male ratio was 2.3. The principal clinical symptoms were peripheral neuropathy (35%), confusion and dementia (30%) and anemia-related manifestations such as asthenia and edemas of the legs (20%). Average hemoglobin was 10.7 +/- 2.5 g/dl and average mean erythrocyte cell volume was 95.5 +/- 13.8 fl. There was an anemia, a leucopenia, a thrombocytopenia and a pancytopenia in respectively 27%, 18%, 15% and 8% of the cases. Average serum vitamin B(12) and homocystein levels were with 138 +/- 42 pg/ml and 22.5 +/- 15.2 micro mol/l. No patient had anti-intrinsic factor antibody and the Schilling's test was normal in all patients. Main disorders associated with FCM were atrophic gastritis (59%), long-term metformin or antiacid intake (17%), chronic alcohol intake (8%) and idiopathic FCM (n = 10). Sixteen patients have been successfully treated with oral crystalline cyanocobalamin (500 +/- 280 micro g/d). CONCLUSIONS: This study shows that: firstly, the Cbl deficiency related to FCM may be responsible of severe neurological and hematologic manifestations in approximately 20% of the elderly patients; secondly, the disorders associated with the FCM are multiple in old age, with mainly atrophic gastritis; and thirdly, in clinical practice, oral cyanoCbl treatment may be successful.

Administration, Oral↗
PubMed2002

Divalproex extended-release versus the original divalproex tablet: results of a randomized, crossover study of well-controlled epileptic patients with primary generalized seizures.

PURPOSE: To compare the safety and efficacy of two formulations of divalproex, extended-release divalproex versus the original divalproex tablet, in adolescent and adult patients with epilepsy. METHODS: Eligible patients were between the ages of 12 and 65 years with primary generalized epilepsy, which was controlled over the month prior to study enrollment with divalproex or valproic acid 1000 mg to 2000 mg/day. The patients were well-controlled; 39 of 43 (91%) had no seizures in the previous year. Patients were randomized to receive 84 days of either divalproex two times a day (b.i.d.)/three times a day (t.i.d.) or extended-release divalproex qd and then (crossed over to) 84 days of the comparator formulation. During the two treatment periods, patients received the same daily dose equivalent of divalproex as was taken during the month prior to study entry. The clinical status of patients was evaluated at a screening visit and at four subsequent visits conducted every 42 days. RESULTS: There was no statistically significant difference between the formulation groups for seizure control rate (95% [41/43] for divalproex and 93% [40/43] for extended-release divalproex). Likewise, the formulation groups were similar based on the incidence of treatment-related adverse events. The most frequently reported (< or =11.4% for either formulation) treatment-related adverse events were asthenia, tremor, nausea, and dizziness. CONCLUSIONS: Extended-release divalproex was similar to divalproex for the treatment of well-controlled, primary generalized epilepsy in terms of overall safety and efficacy parameters.

Adolescent↗
PubMed1998

Phase II trial of cisplatin and gemcitabine in advanced squamous-cell carcinoma of the head and neck.

BACKGROUND: To evaluate the toxicity profile and efficacy of cisplatin combined with gemcitabine in patients with irresectable locally recurrent or metastatic squamous cell carcinoma of the head and neck. PATIENTS AND METHODS: Gemcitabine was given at a dose of 800 mg/m2 on days 1, 8 and 15, plus cisplatin at a dose of 50 mg/m2 on days 1 and 8; every four weeks. RESULTS: Twenty-four patients with a median age of 59 years (range 42-74) were included. All patients were evaluable for toxicity and 22 patients were assessable for response. Eleven cases had advanced recurrent locoregional disease while 13 patients had metastatic disease. One CR (4.7%) and four PR (18%) were observed, for an overall response rate of 22.7% (95% CI: 8%-42%). The main toxicity was hematological: neutropenia grade 3-4 in 28% of the cycles and thrombocytopenia grade 3-4 in 16%. The most significant non-hematological toxicity was asthenia grade 2-3 in 24% of the cycles. CONCLUSIONS: This cisplatin plus gemcitabine combination schedule has a favourable toxicity profile with a discrete activity in patients with locally recurrent or metastatic squamous-cell carcinoma of the head and neck.

Adult↗
PubMed1999

Concurrent conventionally factionated radiotherapy and weekly docetaxel in the treatment of stage IIIb non-small-cell lung carcinoma.

Docetaxel has shown remarkable radiosensitizing in vitro properties. In a previous phase I/II dose escalation study in non-small-cell lung cancer (NSCLC) we observed a high response rate after concomitant boost radiotherapy and weekly docetaxel. The maximum tolerated dose was 30 mg m(-2) week(-1). In the present phase II study we evaluated whether weekly docetaxel and conventionally fractionated radiotherapy could be better tolerated and equally effective in the treatment of locally advanced NSCLC. Thirty-five patients with T3, T4/N2, T3/M0-staged disease were recruited. Docetaxel (30 mg m(-2)) was given as a 30 min infusion once a week. Asthenia and radiation-induced oesophagitis were the main side-effects of the regimen enforcing 2-week treatment delay in 6/35 (17%) patients and minor delay (3-7 days) in another 11/35 (31%) patients. Neutrophil, platelet and haemoglobin toxicity was minimal, but pronounced lymphocytopenia was observed. Complete response (CR) of the chest disease was observed in 12/35 (34%) patients and partial response in 16/35 (46%). Although not statistically significant (P=0.19), a higher CR rate (8/18; 44%) was observed in patients who accomplished their therapy within the scheduled treatment time (44-47 days) as compared to patients that interrupted their treatment for several days due to treatment-related toxicity (CR 4/17; 23%). The overall survival and the local progression-free survival at 1 year was 48% and 60% respectively. We conclude that docetaxel combination with radiotherapy is a promising approach for the management of locally advanced NSCLC that results in high CR rate. Further trials with docetaxel-based radiochemotherapy should integrate accelerated radiotherapy together with cytoprotection.

Adult↗
PubMed2000

Lymph node infection by Trichomonas tenax: report of a case with co-infection by Mycobacterium tuberculosis.

In an 82-year-old woman, presenting with fever and asthenia, cervical adenopathy was noted. Clinical and radiological investigations were fruitless. Laboratory examinations detected a refractory anemia. The lymph node was excised and showed numerous trichomonads on touch preparations. Histologically, the node showed caseous necrosis and macrophagic reaction. Diagnosis of lymph node infection by Trichomonas tenax was made. Three weeks later, culture of the node showed Mycobacterium tuberculosis and let us conclude co-infection. T tenax is usually regarded as a harmless saprophyte of the oral cavity. This exceptional observation shows for the first time an invasive potential of T tenax. It raises questions about links with tuberculosis and refractory anemia.

Aged↗
PubMed2000

A phase I and pharmacokinetic study of the combination of capecitabine and docetaxel in patients with advanced solid tumours.

Capecitabine and docetaxel are both active against a variety of solid tumours, while their toxicity profiles only partly overlap. This phase I study was performed to determine the maximum tolerated dose (MTD) and side-effects of the combination, and to establish whether there is any pharmacokinetic interaction between the two compounds. Thirty-three patients were treated with capecitabine administered orally twice daily on days 1-14, and docetaxel given as a 1 h intravenous infusion on day 1. Treatment was repeated every 3 weeks. The dose of capecitabine ranged from 825 to 1250 mg m(-2) twice a day and of docetaxel from 75 to 100 mg m(-2). The dose-limiting toxicity (DLT) was asthenia grade 2-3 at a dose of 1000 mg m(-2) bid of capecitabine combined with docetaxel 100 mg m(-2). Neutropenia grade 3-4 was common (68% of courses), but complicated by fever in only 2.4% of courses. Other non-haematological toxicities were mild to moderate. There was no pharmacokinetic interaction between the two drugs. Tumour responses included two complete responses and three partial responses. Capecitabine 825 mg m(-2) twice a day plus docetaxel 100 mg m(-2) was tolerable, as was capecitabine 1250 mg m(-2) twice a day plus docetaxel 75 mg m(-2).

Adult↗
PubMed1999

Doxazosin GITS compared with doxazosin standard and placebo in patients with mild hypertension.

Doxazosin, an effective treatment for mild-to-moderate hypertension and benign prostatic hyperplasia, in its standard formulation requires a multiple-step titration regimen to minimize the potential for first-dose effects. A new controlled-release gastrointestinal therapeutic system (GITS) formulation of doxazosin was developed to enhance the pharmacokinetic profile, significantly reducing serum peak-to-trough ratios, thereby minimizing the need for titration. We assessed the efficacy and tolerability of doxazosin GITS compared with doxazosin standard and placebo in a prospective, randomized, double-blind, parallel-group, dose-titration, multicenter study of 392 patients with mild hypertension (blood pressure [BP] < or = 180/95-105 mmHg). Patients were randomized to doxazosin GITS, doxazosin standard, or placebo in 2:2:1 manner. The primary outcome measure was the proportion of patients in the per-protocol analysis (PPA) who achieved goal BP response (sitting BP < or = 90 mmg or 10 mmHg decrease from baseline at 24 h postdose at the final evaluable visit). Goal BP response in the intention-to-treat (ITT) population and prespecified BP and/or heart rate changes in the PPA and/or ITT population were also analyzed. Tolerability was assessed throughout the study. Doxazosin GITS and doxazosin standard produced comparable goal BP responses superior to that of placebo, with 92 of 156 patients (59.0%) on doxazosin GITS and 86 of 152 patients (56.6%) on doxazosin standard in the PPA population achieving goal BP response 24 hours postdose on the final visit, compared with 25 of 70 patients (35.7%) on placebo. Both active treatments produced mean significant BP reductions compared with baseline and placebo (p < 0.001). The most commonly reported side effects were headache, dizziness, and asthenia. No syncope was reported in the doxazosin GITS group; two cases were observed in the doxazosin standard group and one case in the placebo group. Doxazosin GITS was well tolerated and as effective as doxazosin standard in patients with mild hypertension, producing well-tolerated, comparable BP reductions with minimal need for titration. Both active treatments were clinically and statistically superior to placebo.

Adult↗