Weeks Of Maintenance Therapy Research Articles

187 Efficacy and safety of 22 weeks of maintenance therapy with peginterferon alfa-2A (40KD) (PEGASYS™) alone versus peginterferon alfa-2A (40KD) plus ribavirin(COPEGUS™) in naive patients with chronic hepatitis C and genotype 1 who responded to a 24-week course of peginterferon alfa-2A (40KD) plus ribavirin: an open, multicenter, randomized trial

187 Efficacy and safety of 22 weeks of maintenance therapy with peginterferon alfa-2A (40KD) (PEGASYS™) alone versus peginterferon alfa-2A (40KD) plus ribavirin(COPEGUS™) in naive patients with chronic hepatitis C and genotype 1 who responded to a 24-week course of peginterferon alfa-2A (40KD) plus ribavirin: an open, multicenter, randomized trial

Preclinical and clinical assessment of the safety and potential efficacy of thalidomide in heart failure

Background: Inflammatory mediators, especially tumor necrosis factor (TNF), have been implicated in heart failure (HF). Thalidomide has anti-inflammatory properties and selectively inhibits TNF. Thus far, thalidomide or thalidomide analogues have not been evaluated in patients with heart failure. Methods: Thalidomide was assessed in preclinical and clinical studies. First, isolated cardiac myocytes were pretreated with thalidomide or thalidomide analogues, and TNF production was assessed after lipopolysaccharide (LPS) provocation. Second, to determine the safety and potential efficacy of thalidomide, an open-label dose escalation safety study was conducted in seven patients with advanced heart failure. Results: Thalidomide and thalidomide analogues inhibited LPS-induced TNF biosynthesis in cardiac myocytes in a dose-dependent manner. Thalidomide analogues had a greater inhibitory effect on TNF production than did thalidomide. In patients with advanced HF, thalidomide was safe and potentially effective when used at lower doses. However, dose-limiting toxicity was observed in two patients. There was a significant increase in the 6-minute walk distance and a trend toward improvement in left ventricular ejection fraction and quality of life after 12 weeks of maintenance therapy with thalidomide. Conclusions: Taken together these results suggest that thalidomide or its derivatives may be useful in selected patients with HF. This potential needs to be studied in larger clinical trials.

Rabeprazole benefits patients with persistent symptoms after healing of erosive GERD

Purpose: A post hoc analysis was undertaken to assess changes in symptoms after 4 weeks of maintenance therapy in patients with persistent symptoms after healing of erosive esophagitis.

Evaluation of a new once-daily formulation of oxybutynin for the treatment of urinary urge incontinence

Objectives. To evaluate in a 16-center, single-treatment study once-daily controlled-release oxybutynin (Ditropan XL) for urinary urge incontinence. Methods. Two hundred fifty-six participants with urge incontinence or mixed incontinence with a significant urge component were treated. After baseline measurements, participants converting from conventional oxybutynin started Ditropan XL at their previous oxybutynin dose; others started at 5 mg/day. Doses were adjusted until participants reached a maintenance dose that produced continence or the best balance between continence and side effects. This dose was continued for 12 weeks. Effectiveness was assessed by urinary diaries. Results. Effectiveness was achieved across all doses studied (5 to 30 mg/day), with 70.8% of participants using maintenance doses of 5 to 15 mg/day. Mean urge incontinence episodes per week decreased from 18.8 at baseline to 3.9 in maintenance week 1, 2.7 in week 4, and 2.8 at the end of the study. For those participants who reported urge incontinence episodes at baseline but were free of urge incontinence at maintenance week 1, 31% remained free of urge incontinence at every subsequent assessment. Participants who converted from other medications showed symptomatic improvement after conversion. At some time during the study, 58.6% of participants reported dry mouth, with 23.0% of participants rating it moderate or severe. Only 1.6% of participants discontinued the medication because of dry mouth. Conclusions. Ditropan XL treatment reduced the number of incontinence episodes. Maximum benefit was demonstrated by maintenance week 4 and was sustained through 12 weeks of maintenance therapy.

Improved outcome with delayed intensification for children with acute lymphoblastic leukemia and intermediate presenting features: a Childrens Cancer Group phase III trial.

The Berlin-Frankfurt-Munster (BFM) 76/79 trial of acute lymphoblastic leukemia (ALL) in children produced impressive disease-free survival (DFS) rates with a protocol that began with 8 weeks of intensive therapy, followed by 8 weeks of maintenance therapy, and then another 6 weeks of intensive treatment. The current study was conducted to determine the relative contributions of each of these periods of intense therapy on the DFS rates of ALL patients with intermediate presenting features. In addition, due to concerns regarding the toxicity of CNS irradiation, we compared cranial irradiation (CXRT) with intrathecal methotrexate (IT MTX) administered during induction and consolidation to IT MTX during all phases of the treatment program. Between May 1983 and April 1989, more than 1,600 children with ALL and intermediate presenting features, as defined by the Childrens Cancer Group (CCG), were entered into a randomized trial that tested four systemic therapy regimens and two CNS programs. The results with a median follow-up of 57 months show that systemic regimens with a delayed intensification (Delint) phase of therapy had a 5-year event-free survival (EFS) rate of 73% compared with the control regimen EFS rate of 61% (p = .006). For children less than 10 years of age, standard three-drug induction and Delint produced a 77% 5-year EFS. IT MTX during all phases of therapy provided CNS protection comparable to the CXRT regimen in children less than 10 years of age. Children 10 years of age or older appear to have a better EFS rate with intensive induction, Delint, and CXRT. Delint improves the EFS rate of children with ALL and intermediate presenting features. Maintenance IT MTX can be safely substituted for CXRT for presymptomatic CNS therapy in children with intermediate-risk characteristics less than 10 years of age.

Assessment of Quality of Life by Patient and Spouse During Antihypertensive Therapy With Atenolol and Nifedipine Gastrointestinal Therapeutic System

To evaluate differences in efficacy, safety, and quality of life, 394 male patients with mild-to-moderate hypertension were randomized to receive 20 weeks of either atenolol or nifedipine gastrointestinal therapeutic system (GITS) in a multicenter double-blind trial. A four-week placebo washout was followed by 8 weeks of titration and 12 weeks of maintenance therapy. Quality-of-life evaluation included clinical assessments by the patient and parallel take-home assessments by patient and spouse. Blood pressure was controlled equally in both groups. The total incidence of adverse reactions was similar in both groups, but a greater percentage of nifedipine GITS patients withdrew due to peripheral edema. Patients completing 20 weeks of therapy demonstrated a more favorable quality-of-life profile (P less than .05) for nifedipine GITS over atenolol in psychosocial (P less than .01), well-being (P less than .05), general affect (P less than .05), emotional ties (P less than .01), emotional control (P less than .05), vitality (P less than .05), and leisure (P less than .05) scores. Treatment differences were particularly pronounced for patients over 50 years of age and were not fully detectable until after 14 weeks of therapy. Deterioration in quality of life was associated with withdrawal. Spouses of younger patients receiving atenolol reported deterioration in sexual satisfaction as compared to spouses of patients taking nifedipine GITS (P less than .02). Thus age, length of trial, and third-party observation are important factors in quality-of-life assessment. Comparison of adverse reactions provides an incomplete measure of how well a drug is tolerated. In contrast, findings indicate that even subtle CNS-mediated effects on mood and well-being can be detected by quality-of-life evaluation.

Foscarnet treatment of cytomegalovirus retinitis in patients with the acquired immunodeficiency syndrome

Ten patients with acquired immunodeficiency syndrome with newly diagnosed cytomegalovirus (CMV) retinitis were treated with an induction regimen of intravenous foscarnet, 60 mg/kg of body weight, administered as a 2-h infusion and repeated every 8 h for 14 days. At the end of induction, 9 of 10 patients had stabilized (no new retinal lesions and stable old lesions [7 patients]) or improved (decreased retinal opacification [2 patients]). All eight patients with CMV in urine or blood upon entry into the study had negative urine and blood cultures at the end of induction. After induction therapy, seven patients continued maintenance foscarnet therapy, 60 mg/kg as a single daily infusion, 5 days/week. In six patients, retinal lesions increased in size after 2 to 32 weeks of maintenance therapy. One was invaluable because a retinal detachment developed. Only 9 of 42 blood and urine cultures obtained during maintenance foscarnet therapy yielded CMV, compared with 7 of 14 obtained prior to the initiation of foscarnet induction therapy (P = 0.04). Foscarnet toxicity was mild and infrequent: elevation in serum creatinine by 0.5 to 1.3 mg/dl over the base line (two patients), muscle twitching (three patients), hemoglobin decrease by 1 mg/dl (two patients), nausea (two patients), absolute neutrophil count decrease by 50% (one patient), rise in serum phosphorus to greater than 5.5 mg/dl (four patients), and proteinuria (two patients). Intermittently administered intravenous foscarnet appears to be an effective, relatively nontoxic therapy for CMV retinitis. Additional studies to determine the optimal dosage for maintenance therapy are needed, as are comparative trials with ganciclovir.

Correlations Between the Cardiovascular Effects of Pimobendan and Plasma Concentrations of the Parent Compound and of Its Major Active Metabolite, UD-CG 212 CL, in Patients with Congestive Heart Failure

Pimobendan was administered orally (10 mg single dose on day 1, then 5 mg twice daily for 4 weeks) to nine patients with chronic heart failure undergoing hemodynamic monitoring. The time course of changes in plasma concentrations of pimobendan and of its major active metabolite. UD-CG 212 CL. was similar on days 1.2. and 28. Pimobendan plasma levels peaked 1.5–2.0 h after drug intake; plasma concentrations of UD-CG 212 CL reached a maxiμm 1 h later; the terminal half-life of pimobendan in plasma varied between 1.44 ± 0.94 h on day 1 and 1.19 ± 0.36 h on day 2. Initially, cardiovascular variables changed with increasing plasma drug levels and reached a maxiμm 4 h after pimobendan intake: later, we found no correlation between plasma concentrations and hemodynamic effects. A steady state of hemodynamic improvement was achieved after 4 weeks of maintenance therapy with pimobendan. Baseline pulmonary capillary wedge pressure dropped from 16 ± 7 mm Hg on day 1 to 5 ± 3 mm Hg at noon on day 28 (–69%: p < 0.001), and baseline cardiac index increased from 2.2 ± 0.5 L/min/m2 on day 1 to 2.7 ± 0.9 L/min/m2 on day 28 ( + 23% p < 0.01). Pimobendan is a long-acting drug that effectively improves cardiac performance in patients with chronic congestive heart failure

Correlations Between the Cardiovascular Effects of Pimobendan and Plasma Concentrations of the Parent Compound and of Its Major Active Metabolite, UD-CG 212 CL, in Patients with Congestive Heart Failure

Pimobendan was administered orally (10 mg single dose on day 1, then 5 mg twice daily for 4 weeks) to nine patients with chronic heart failure undergoing hemodynamic monitoring. The time course of changes in plasma concentrations of pimobendan and of its major active metabolite. UD-CG 212 CL, was similar on days 1, 2, and 28. Pimobendan plasma levels peaked 1.5-2.0 h after drug intake: plasma concentrations of UD-CG 212 CL reached a maximum 1 h later; the terminal half-life of pimobendan in plasma varied between 1.44 +/- 0.94 h on day 1 and 1.19 +/- 0.36 h on day 2. Initially, cardiovascular variables changed with increasing plasma drug levels and reached a maximum 4 h after pimobendan intake; later, we found no correlation between plasma concentrations and hemodynamic effects. A steady state of hemodynamic improvement was achieved after 4 weeks of maintenance therapy with pimobendan. Baseline pulmonary capillary wedge pressure dropped from 16 +/- 7 mm Hg on day 1 to 5 +/- 3 mm Hg at noon on day 28 (-69%; p less than 0.001), and baseline cardiac index increased from 2.2 +/- 0.5 L/min/m2 on day 1 to 2.7 +/- 0.9 L/min/m2 on day 28 (+23%; p less than 0.01). Pimobendan is a long-acting drug that effectively improves cardiac performance in patients with chronic congestive heart failure.

Antihypertensive Therapy with Once‐daily Administration of Terazosin, a New Alpha1‐adrenergic‐receptor Blocker

The antihypertensive activity of terazosin, an investigational alpha 1-adrenergic-receptor blocker, and its effect on blood lipids were compared with placebo in a double-blind study. After a 3-week placebo baseline period, patients were randomized to receive terazosin (n = 22) or placebo (n = 16). The dose of terazosin was titrated over 2 weeks to a maintenance dosage of 10 mg once daily for 4 weeks. Antihypertensive efficacy was assessed: (1) at the end of the 24-hour dosing interval by comparing the average blood pressure (BP) after 3 and 4 weeks of maintenance therapy to the average BP after 2 and 3 weeks of placebo therapy, and (2) for 3 hours after drug ingestion at the final visit in comparison to the predose BP at that visit. At the end of the 24-hour dosing interval, 10 mg of terazosin reduced the mean supine systolic BP from 155.6 to 152.2 mm Hg and mean supine diastolic BP from 101.9 to 99.0 mm Hg (p less than 0.05). During the 3 hours after drug ingestion, mean supine systolic and diastolic pressures decreased maximally from 151.8 to 142.7 mm Hg (p less than 0.05) and from 99.5 to 91.0 mm Hg (p less than 0.05) respectively. No supine BP reduction differed significantly from the placebo response. During terazosin therapy there was a nonsignificant increase in mean body weight of 1.4 +/- 2.9 kg and no change in blood lipids. Thus the drug demonstrated greater antihypertensive activity 1-3 hours after ingestion than at the end of the 24-hour dosing interval.(ABSTRACT TRUNCATED AT 250 WORDS)

Use of Nifedipine as an Adjunct to Current Antihypertensive Therapy

Ten hypertensive patients with poor responses to standard antihypertensive therapy were treated with the calcium channel antagonist nifedipine in an attempt to obtain better BP control. The drug was highly effective in significantly lowering BP immediately (average decrease, 58/29 mm Hg) and after three to eight weeks of maintenance therapy (average decrease, 49/27 mm Hg), with no significant change in heart rate observed at either time. No adverse interactions between nifedipine and other concurrent medications, including digoxin and beta-adrenergic blockers, were noted. Drug-related side effects of tachycardia or flushing necessitated the withdrawal of nifedipine therapy in two patients. We conclude that nifedipine may be safely employed in an outpatient setting as a useful adjunct to current antihypertensive drug regimens.

Enalapril: A new angiotensin-converting enzyme inhibitor in chronic heart failure: Acute and chronic hemodynamic evaluations

Hemodynamic effects of the new oral angiotensin-converting enzyme inhibitor, enalapril, were evaluated acutely in 15 patients with chronic heart failure and in 7 patients after 4 weeks of maintenance therapy. Initial hemodynamic effects were characterized by a significant increase in cardiac index (from 2.1 +/- 0.7 to 2.6 +/- 0.7 liters/min per m2) and a decrease in pulmonary capillary wedge pressure (from 30 +/- 6 to 24 +/- 7 mm Hg), right atrial pressure (from 14 +/- 5 to 11 +/- 4 mm Hg), mean arterial pressure (from 96 +/- 16 to 80 +/- 17 mm Hg) and systemic vascular resistance (from 1,820 +/- 480 to 1,200 +/- 410 dynes . s . cm-5) without any significant change in heart rate, pulmonary artery pressure and pulmonary vascular resistance. During maintenance therapy, the dose of diuretic drugs had to be increased because of systemic venous hypertension. Repeat hemodynamic study showed that after chronic therapy, cardiac index (2.1 +/- 0.7 vs. 3.0 +/- 0.08 liters/min per m2) and stroke volume index (24 +/- 10 vs. 36 +/- 7 ml/m2) remained elevated and pulmonary capillary wedge pressure was lower than control (30 +/- 6 vs. 16 +/- 6 mm Hg), indicating sustained improvement in left ventricular performance. Plasma renin activity increased and plasma norepinephrine levels decreased after enalapril therapy and these humoral changes persisted during maintenance therapy. All patients receiving chronic therapy had symptomatic improvement. Significant hypotension, which occurred in five patients at the initiation of therapy, appears to be the major side effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical Trial Comparing Timolol Ophthalmic Solution to Pilocarpine in Open-Angle Glaucoma

A ten-week, double-masked, randomized, clinical trial compared timolol ophthalmic solution and pilocarpine in the therapy of open-angle glaucoma. Timolol decreased the intraocular pressure at least as much as pilocarpine and did not induce miosis, accommodative spasm, or other annoying side effects. The pulse was slowed by timolol, but blood pressure was unaffected. Significant decreases in intraocular pressure were still present after ten weeks of maintenance therapy with the same concentration of drug.

IMMUNOGLOBULINS IN ACUTE LEUKEMIA IN CHILDREN

Levels of immunoglobulins G, A and M were studied in 120 cases of acute leukemia between 7 months and 16 years of age. Eighty-three cases had acute stem cell leukemia (ALL) and 37 had acute myelogenous, monocytic or atypical leukemia. (Estimations during radial immunodiffusion were done at diagnosis, after induction of remission and after 6 weeks of maintenance therapy.) In ALL the initial levels of all 3 immunoglobulins at diagnosis and before starting therapy, tended to be low in spite of the prevalence of infection. Further decreases occurred after induction, but thereafter the levels increased to reach pre-therapy levels despite maintenance therapy. Levels of IgG below the 350-380 mg% had a bad prognostic significance. In patients receiving periodic central nervous system (CNS) irradiation, the IgA levels were significantly lower than in patients not so treated, but the incidence of intercurrent infections was not significantly altered. In the group of myelogenous or atypical leukemia, high or normal initial levels of immunoglobulins were found in all but two at diagnosis. The trend during induction and maintenance followed the same pattern as in ALL.

Metabolic effects of ethacrynic acid in the aged.

AbstractEthacrynic acid was given to 41 aged men and women who had previously been treated with thiazides for congestive heart failure. Twenty‐three of these patients had diabetes. After ten weeks of maintenance therapy with ethacrynic acid, there were no statistically significant changes in the levels of blood urea nitrogen, serum uric acid, chloride, sodium and potassium. Glucose tolerance was not adversely affected; rather, glucose tolerance improved (P &lt; .05) in the 20 diabetic patients tested. Of the 41 patients, 7 had gastrointestinal symptoms of mild to moderate severity for one to three days, but when ethacrynic acid was started again these symptoms did not recur. Ethacrynic acid, as used in the present study, would appear to be an effective, relatively safe diuretic, particularly well suited for long‐term use in patients with diabetes mellitus.

Adrenal cortex and renal pressor function.

The pressor response of the nephrectomized rat to the injection of kidney extracts and to a renal graft, was used as an index of the renal content and secretion of pressor substances during adrenal insufficiency or treatment with corticosteroids. Adrenalectomy caused an elevation of both content and secretion, which was best demonstrated after two to three weeks of maintenance therapy. Treatment with cortisone and cortisol decreased slightly but significantly the secretion of pressor substances without altering renal content. ACTH had no effect on either function. Sequential studies of content and secretion of pressor substances during treatment with DCA plus salt showed first a rapid disappearance of prossor activity from renal vein blood followed by a decrease in renal content to near zero levels; DCA without excess salt elicited the same effects but more gradually; administration of 1% saline alone decreased secretion without altering content. It is concluded that salt active corticosteroids specifically inhibit the formation and secretion of renal pressor substances and that determination of the index of secretion constitutes a more reliable and sensitive indicator of the renal pressor function than determination of the pressor activity in kidney extracts.