肾移植患者应用咪唑立宾与麦考酚酸酯2种三联免疫抑制方案的疗效比较

目的:观察咪唑立宾(MZR)的免疫抑制效果及安全性,采用MZR替代麦考酚酸酯(MMF),比较环孢素A(CsA)+MZR/MMF+泼尼松龙(Pre)两种三联免疫抑制治疗的疗效。方法:尸体肾移植患者70例,按手术顺序交替登记MZR组和MMF组。移植后采用CsA+MZR/MMF+Pre三联免疫抑制疗法,MZR组剂量为200mg.d-1(体重>60kg)或150mg.d-1(体重<60kg);MMF组剂量为1500mg.d-1(体重>60kg)或1000mg.d-1(体重<60kg)。观察肾移植术后1年的人/肾存活率、急性排斥反应发生率及治疗逆转率、感染发生情况及药物毒副作用。结果:全部病例术后随访至少1年,MZR组和MMF组的急性排斥反应发生率分别为17.1%和11.4%,两组之间无显著性差异。MZR组和MMF组肺部感染的发生率分别为8.6%和48.6%,MMF组的发生率显著升高。血尿酸升高的发生率两组之间比较未见显著性差异,MZR组在术后24,36,48周时血尿酸的水平要高于MMF组。MZR组的持续用药率显著高于MMF组。结论:MZR可以与钙调神经素阻滞剂、激素联合应用于肾移植患者,具有一定的安全性和有效性,不良...     

The effects of cardiac transplantation and cyclosporine therapy on digoxin pharmacokinetics.

Most patients needing cardiac transplantation are treated with digoxin for heart failure. Because of its narrow therapeutic range, even recommended doses of digoxin may cause severe toxicity. Several drugs, including quinidine, amiodarone, verapamil, and propafenone can interact with digoxin, leading to toxic accumulation of the glycoside. The authors have recently reported two cases of severe digitalis toxicity after the initiation of cyclosporine treatment in patients awaiting cardiac transplantation. A preliminary study on two additional patients suggested that cyclosporine reduced the plasma clearance and volume of distribution of digoxin. To assess the mechanism of this interaction, the authors studied digoxin pharmacokinetics in patients awaiting cardiac transplantation and again after the surgery, during chronic cyclosporine therapy. To separate the effects of transplantation and cyclosporine on digoxin pharmacokinetics, pharmacokinetic studies were subsequently performed in dogs to allow controlled experimental conditions for evaluation of the digoxin-cyclosporine interaction.     

肾移植术后抗感染治疗期间环孢素血药浓度监测与剂量调整1例

目的:分享肾移植术后患者抗感染治疗期间环孢素剂量调整的经验。方法:通过1例实际病例,并结合文献复习,总结肾移植术后使用阿奇霉素、伏立康唑抗感染治疗期间环孢素血药浓度监测与剂量调整的经验。结果:肾移植术后抗感染治疗时,大环内酯类药物如果无法代替,选用阿奇霉素可能是恰当的选择,必要时需要通过环孢素血药浓度监测来调整药物剂量;伏立康唑与环孢素的相互作用明确,两药联用时,必须通过环孢素血药浓度监测来调整其剂量。结论:肾移植术后,患者使用环孢素治疗期间,临床药师应该从与其有相互作用的药物中选择影响相对较小的药物;在药物剂量调整时,应该在抗感染药物和环孢素之间确定调整的目标药物,从而给临床医师提供合理建议。     

Combination therapy with diltiazem plus CsA/MMF/Pred or CsA/Aza/Pred triple immunosuppressive regimens for use in clinical kidney transplantation in Northwestern China

Objective

The effects of diltiazem on 1692 kidney transplant recipients under the immunosuppressive regimen of cyclosporine A (CsA) in combination with either mycophenolate mofetil or azothioprine were assessed. The two treatment groups were compared for blood concentrations of CsA, the extent of acceptable dosage reduction for the maintenance of immunotherapy, potential effects of kidney protection, and promotion of graft function.

Method

We monitored changes of blood concentrations of CsA in the two different patient treatment groups for post-transplant graft function, episodes of acute rejection, and hepatic and renal toxicity in 1640 renal transplant recipients after treatment with diltiazem.

Results

In patients treated with the triple immunosuppressive regimen consisting of CsA, azothioprine, and prednisolone (Pred), the sub-group of patients receiving the diltiazem treatment saw a significantly reduced CsA dosage in comparison to the non-diltiazem group (control group 1) (P?<?0.05), but the blood concentrations of CsA of the diltiazem group were higher than those of control group 1 (P?<?0.01). Of the patients treated with CsA, mycophenolate mofetil, and Pred, the sub-group of patients also treated with diltiazem showed similar effects: CsA dosage was reduced (P?<?0.01) and the blood concentrations of CsA significantly increased (P?<?0.01) in comparison with those of control group 2. In addition, recovery time of graft function decreased to 4.7?±?1.8?days and 3.9?±?1.4?days in the two diltiazem treatment groups, respectively (P?<?0.05), and the rate of acute rejection decreased to 21 (p?<?0.05) and 7.9% (P?<?0.01), respectively.

Conclusion

In our cohort of renal transplantation patients, co-administration of CsA and diltiazem increased CsA blood concentration, thereby resulting in a reduction in its required dosage treatment, which lightened the patients?? economic burden while improving primary and long-term kidney function by promoting the recovery of graft function and decreasing hepatic and renal toxicity. The co-administration of diltiazem may also reduce the rate of acute rejection, especially in patients who also receive the triple immunosuppressive regimen consisting of CsA, mycophenolate mofetil, and Pred.     

Comparison of nonspecific radioimmunoassay, high-performance liquid chromatography, and fluorescence polarization immunoassay for cyclosporine monitoring in renal transplantation

Three methods, i.e., nonspecific radioimmunoassay (RIA; Incstar), fluorescence polarization immunoassay (FPIA; TDx Abbott), and high-performance liquid chromatography (HPLC), have been used for monitoring cyclosporine blood levels in renal transplantation patients. The levels obtained from 135 samples showed a modest correlation between RIA and HPLC, FPIA and HPLC, RIA and FRIA. The mean ratios of RIA to HPLC, FPIA to HPLC, and RIA to FPIA were 2.96, 4.14, and 0.73. The significant variations in cyclosporine levels result from the cross-reaction of antibody with some cyclosporine metabolites, by which these two methods often overestimate the true blood cyclosporine level. HPLC is a more effective and reliable method for pharmacokinetic studies and blood level monitoring of cyclosporine in clinical practice.     

One-week triple therapy with omeprazole, amoxycillin and either clarithromycin or metronidazole for cure of Helicobacter pylori infection

Aim: The present study was designed to evaluate the efficacy and tolerability of 1-week triple therapy regimens for Helicobacter pylori .
Methods: In two consecutive series, 120 patients with proven H. pylori infection and peptic ulcer disease or functional dyspepsia were treated with either omeprazole 20 mg b.d., amoxycillin 1 g b.d. and clarithromycin 250 mg b.d. (OAC; n=60) or with omeprazole 20 mg b.d., amoxycillin 1 g b.d. and metronidazole 400 mg b.d. over 1 week (OAM; n=60). H. pylori infection was assessed by rapid urease test, culture and histology before and 4 weeks after cessation of the eradication therapy.
Results: H. pylori eradication succeeded in 53 out of 60 patients by omeprazole–amoxycillin–clarithromycin (OAC) (88%; 95% CI 77–95%) and in 47 out of 60 patients by omeprazole–amoxycillin–metronidazole (OAM) (78%; 95% CI 66–88%) (P=0.22). Nine patients of each group available for follow-up reported adverse events (15.0 and 15.5%, respectively) without necessity of discontinuation of the study medications. Serious adverse events were not observed.
Conclusions: Simple and convenient 1-week triple therapies consisting of omeprazole, amoxycillin and either clarithromycin or metronidazole are sufficiently effective in eradicating H. pylori infection.     

短期三联疗法对幽门螺杆菌根治的效果

目的：了解含有质子泵抑制剂兰索拉唑的短期三联疗法对幽门螺杆菌根治的效果。不良反应及溃疡愈合和得发情况。方法：对１５２例胃镜证实为消化性溃疡患者，经胃粘膜活检脲素酶法测定ＨＰ，阳性者用ＰＰＩ兰索拉唑３０ｍｇ ｄｉｄ，阿莫西林５００ｍｇ ｂｉｄ及克拉霉素５００ｍｇ ｂｉｄ三联治疗７ｄ、分别于治疗结束后的４ｗｋ及６ｍｏ复查胃镜及ｃｌｏ－ｔｅｓｔ，并记录根治治疗的不良反应。     

Abbreviated pharmacokinetic profiles in area-under-the-curve monitoring of cyclosporine therapy in de novo renal transplant patients treated with Sandimmune or Neoral. Neoral study group

Trough cyclosporine (CsA) blood levels obtained just before administration of the next dose are monitored to guide dosage adjustments. However, these levels may not be the best indicator of total drug exposure. In a study of de novo renal transplant patients, pharmacokinetic profiles of CsA after administration of the traditional CsA formulation (Sandimmune [CsA-SIM] Novartis, E. Hanover, NJ) or the new formulation, cyclosporine capsules for microemulsion (Neoral [CsA-ME] Novartis, E. Hanover, NJ), were compared at 1, 4, 8, and 12 weeks posttransplantation under fasting and fed conditions. The data were analyzed to assess the degree of correlation between total drug exposure, indicated by the area under the concentration-versus-time curve at the end of a 12-hour dosing interval (AUC12h), and drug exposure calculated from concentrations obtained at different time points (abbreviated AUC [AAUC]). With AAUCs calculated from trough levels and levels at 4 hours postdose, the average degree of correlation with AUC12h was r = 0.915 for CsA-ME and r = 0.853 for CsA-SIM. The degree of correlation was smaller with CsA-SIM and additional sampling times may be required. With CsA-ME, these two sampling time points appear to provide a reliable indication of total CsA exposure; CsA-ME may thus provide advantages in terms of blood level monitoring and patient management.     

Study of blood cyclosporine after kidney or bone marrow transplantation. Comparison of immunofluorescence and radioimmunoassay

The apparition of cyclosporine, immunodepressive drug, has largely improved the organ transplantations. However, the range of blood concentrations must be defined to allow the efficacity of cyclosporine therapy and to avoid toxic reactions, because there are very important variations for a same dosage according to the individuals and the diseases. Relative to the low concentrations to be determined (about one hundred ng/ml), the most useful methods for cyclosporine measurement are based on immunochemical assays. This work compare the two methods: radioimmunoassay (RIA) and fluorescence polarization immunoassay (FPIA) simultaneously performed on several hundred samples. A very significant correlation exists between the two techniques (r = 0,80). The advantages of immunofluorescent assay consists in rapidity, sensibility and facility to realize emergency analysis.     

Concentrations of mycophenolic acid and glucuronide metabolites under concomitant therapy with cyclosporine or tacrolimus

Mycophenolate mofetil [MMF, the prodrug of mycophenolic acid (MPA)] is usually administered at double doses with cyclosporine than with tacrolimus because it is believed that MPA exposure is lower during cyclosporine therapy. This study aimed to compare 12 hour, steady-state concentration-time profiles of MPA and its phenol- and acyl-glucuronide metabolites (MPAG and AcMPAG, respectively) in stable kidney transplant recipients maintained either on cyclosporine (n = 12) or tacrolimus (n = 12). During the absorption phase in the cyclosporine group, dose-normalized concentrations of total and free MPA were significantly higher but the overall area under the concentration-time curve (AUC0-12) was not significantly different. Additionally, exposure to AcMPAG was higher in the cyclosporine group (P < 0.05). Ten of 12 patients in the cyclosporine group were on ketoconazole therapy; however, the exposure to MPA or MPAG was not different when MMF was given orally to Sprague-Dawley rats with or without ketoconazole. In conclusion, cyclosporine modulates the disposition of MPA and metabolites differently from tacrolimus; however, patients on cyclosporine may not require double doses of MMF to achieve the same exposure.     

雷贝拉唑与奥美拉唑三联疗法治疗十二指肠球部溃疡的对比研究

目的 :通过与奥美拉唑比较 ,观察雷贝拉唑三联疗法治疗十二指肠球部溃疡的疗效。方法 :5 3例患者随机分为两组 ,分别给予以雷贝拉唑 (RAC)和奥美拉唑 (OAC)为主的三联疗法 ,用药结束后复查胃镜并检测 Hp。同时于用药后 1d、2 d、3d、7d、14 d对临床症状进行评估。结果 :4 7例患者完成全部治疗方案。溃疡愈合率 :RAC组为 92 .3% ,OAC组为 76 .2 % ,RAC组高于 OAC组 ,两组之间差异有显著性 (P<0 .0 5 )。 Hp清除率 :RAC组为 85 .4 % ,OAC组为 76 .2 % ,两组之间差异无显著性。两组均能有效改善症状。结论 :两组治疗方案均能有效清除 Hp和缓解症状 ,RAC组溃疡愈合率较 OAC组为高     

A prospective study of cyclosporine concentration in relation to its therapeutic effect and toxicity after renal transplantation.

1. Cyclosporine (CsA) concentrations in plasma and whole blood were monitored prospectively in 66 consecutive kidney transplant recipients for 6 months after transplantation or until graft loss. Immunosuppression was based on treatment with CsA and prednisolone in 27 patients and CsA, azathioprine and prednisolone in 39 patients. 2. Whole blood and plasma samples (separated at 37 degrees C) were collected 10-12 h after CsA dosage twice weekly over the first 3 months and thereafter once weekly. CsA concentrations were measured by high pressure liquid chromatography (h.p.l.c.) in plasma, by specific and non-specific monoclonal radioimmunoassays (r.i.a.) in whole blood, and by polyclonal r.i.a. and polyclonal fluorescence polarization immunoassay (f.p.i.a.) in whole blood and plasma. 3. There were no differences between the treatment schedules regarding graft or patient survival, occurrence of acute rejection, nephrotoxicity or infection. 4. CsA concentrations were significantly lower at the time of acute rejection than one week earlier based on all of the analytical methods used except f.p.i.a. 5. The lowest CsA concentration, recorded during the first month after transplantation, was significantly lower in patients with than in patients without experience of acute rejection episodes when the CsA concentrations were measured by polyclonal r.i.a. in whole blood and plasma and by specific and non-specific monoclonal r.i.a. in whole blood, but not by h.p.l.c. in plasma or polyclonal f.p.i.a. in whole blood or plasma. 6. The highest CsA concentration recorded during the second post-transplantation month, was higher in patients with acute nephrotoxicity than in those without nephrotoxicity when CsA was measured by specific monoclonal r.i.a. in whole blood (471 +/- 409 ng ml-1 vs 327 +/- 150 ng ml-1, P less than 0.05), but not by the other methods. 7. The mean plasma h.p.l.c. concentration of CsA measured by h.p.l.c. during the first month after transplantation was significantly higher in patients who suffered from systemic infection than in patients who did not (116 +/- 70 ng ml-1 vs 82 +/- 52 ng ml-1; P less than 0.05). 8. Thus, significant relationships between CsA concentrations and clinical events were apparent using assay methods specific for CsA as well as using polyclonal r.i.a., but not using polyclonal f.p.i.a. When h.p.l.c. was used, however, plasma drug concentrations were often below the limit of determination. Our results suggest that specific analysis of CsA in whole blood allows the best distinction between patients who respond favourably and less favourably to treatment with CsA.     

A network meta-analysis of the efficacy of belatacept,cyclosporine and tacrolimus for immunosuppression therapy in adult renal transplant recipients

Belatacept is a first in-class co-stimulation blocker developed for primary maintenance immunosuppression following renal transplantation. The objective of this study was to estimate the efficacy of belatacept relative to tacrolimus and cyclosporine among adults receiving a single kidney transplant.

A systematic review was conducted of randomized clinical trials (RCTs) published between January 1990 and December 2013 using EMBASE, MEDLINE, the Cochrane Central Register of Controlled Trials, and unpublished study reports from two belatacept RCTs. Bayesian network meta-analysis (NMA) methods were used to compare the efficacy measures, mortality, graft loss, acute rejection and glomerular filtration rate (GFR). Heterogeneity was quantified using statistical metrics and potential sources were evaluated using meta-regression and subgroup analysis.

A total of 28 RCTs comparing tacrolimus with cyclosporine, and three comparing belatacept with cyclosporine, were identified.

All three agents provided comparable graft and patient survival, despite a higher risk of acute rejection associated with belatacept and cyclosporine. Belatacept was associated with significant improvement in GFR versus cyclosporine. Compared with tacrolimus, this difference was clinically meaningful yet statistically non-significant. The probability of being the best treatment was highest for belatacept for graft survival (68%), patient survival (97%) and renal function (89%), and highest for tacrolimus for acute rejection (99%).Variability in donor, recipient, and trial characteristics was present in the included RCTs; however, minimal statistical heterogeneity was detected in the analysis of acute rejection, graft or patient survival, and none of the characteristics were found to be significantly associated with relative effect. Although the direction of effect of immunosuppressants on GFR was consistent across RCTs, precise estimation of its magnitude was limited by a small number of RCTs and heterogeneity in relative effect sizes.

Clinicians often seek an alternative to CNIs due to their nephrotoxic effects. The results of this indirect comparison indicate that belatacept is an effective immunosuppressive agent in renal transplantation among adults.     

Short-term triple therapy with lansoprazole 30 mg or 60 mg, amoxycillin and clarithromycin to eradicate Helicobacter pylori

BACKGROUND: We investigated the efficacy of 30 vs. 60 mg lansoprazole daily in a 1-week triple therapy for eradication of Helicobacter pylori in a prospective randomized study. METHODS: Two hundred and fifteen consecutive out-patients with peptic ulcer disease or non-ulcer dyspepsia, in whom H. pylori infection was confirmed by histology and/or a urease biopsy test, were randomly assigned to a 1-week treatment with either 15 mg lansoprazole b.d. (LAC15 group) or 30 mg lansoprazole b.d. (LAC30 group) in combination with 1 g amoxycillin b.d. and 500 mg clarithromycin b.d. RESULTS: Eradication of H. pylori was successful in 87% (per protocol) and 82% (intention-to-treat) of the patients with LAC15 and in 94% (per protocol) and 87% (intention-to-treat) of the patients with LAC30. The difference was not significant. In both treatment groups, all peptic ulcers were healed at the check-up. Adverse effects were seen in 11 patients of the LAC15 group and 10 patients of the LAC30 group: they caused discontinuation of the therapy in four of the LAC15 group and two patients of the LAC 30 group. CONCLUSIONS: A 7-day triple therapy using lansoprazole (LAC15) is an efficient and economical regimen for the eradication of H. pylori.     

Single vs. double dose of a proton pump inhibitor in triple therapy for Helicobacter pylori eradication: a meta-analysis

BACKGROUND: Triple therapies combining a double dose of proton pump inhibitor plus two antibiotics are the standard treatment for Helicobacter pylori infection. Some reports suggest that the use of half the dose of proton pump inhibitor is equally effective. AIM: To compare the efficacy of a single vs. double dose of proton pump inhibitor in triple therapy. METHODS: We conducted a MEDLINE search. The search strategy included the words (pylori) AND (triple, PPI, proton pump, omeprazole, rabeprazole, pantoprazole, lansoprazole, clarithromycin, amoxicillin, amoxycillin or metronidazole). Abstracts of the articles obtained and papers presented at the European Helicobacter pylori Study Group and American Gastroenterological Association congresses from 1996 to 2001 were examined. Inclusion criteria were: (i) randomized studies with at least two branches of triple therapy including a proton pump inhibitor and two standard antibiotics; (ii) branches could differ only in terms of proton pump inhibitor dosage. A meta-analysis was conducted using conventional shareware (Review Manager 4.1). RESULTS: Thirteen studies met the inclusion criteria with a total of 2391 patients. Cure rates with double doses of proton pump inhibitor were higher in both the intention-to-treat analysis (83.9% vs. 77.7%; Peto odds ratio, 1.51; 95% confidence interval, 1.23-1.85; P < 0.01) and per protocol analysis (89% vs. 81%; Peto odds ratio, 1.96; 95% confidence interval, 1.55-2.47; P < 0.01). CONCLUSION: Triple therapies containing a single dose of proton pump inhibitor are less effective than those containing a standard double dose of proton pump inhibitor.     

奥美拉唑与埃索美拉唑三联疗法治疗消化性溃疡的系统综述与成本效果分析

目的：通过系统综述和药物经济学的相关方法对奥美拉唑三联疗法与埃索美拉唑三联疗法治疗消化性溃疡的有效性、安全性和经济性进行评价,为临床治疗消化性溃疡用药提供参考和建议;方法：通过Meta分析比较两种治疗方案的疗效和安全性,构建决策树模型,对2种治疗方案治疗消化性溃疡进行成本效果分析,并进行单因素敏感性分析和概率敏感性分析。结果：Meta分析结果显示,在疗效方面,埃索美拉唑三联疗法略优于奥美拉唑三联疗法（幽门螺杆菌根除率：RR=0.93,P=0.03）,安全性方面,2种方案无显著性差异（不良反应发生率：RR=0.91,P=0.19）,均具有较好的安全性;药物经济学评价结果显示,相比于奥美拉唑三联疗法,埃索美拉唑三联疗法的ICER值为2 609.00元,敏感性分析结果与基础分析结果基本一致,说明基础分析结果较为稳健。结论：埃索美拉唑三联疗法治疗消化性溃疡的疗效略优于奥美拉唑三联疗法,但相比于奥美拉唑三联疗法,埃索美拉唑三联疗法的ICER值过高,因此奥美拉唑三联疗法治疗消化性溃疡更具有经济性。     

Impaired prednisolone sensitivities of the endocrine system and peripheral-blood lymphocytes are closely related to clinical incidence in renal transplantation.

Endocrine- and immune-responses to prednisolone and their relation to clinical incidence were assessed in 19 renal transplant recipients. All of the patients were treated with prednisolone and cyclosporin. Response of the hypothalamic-pituitary-adrenal (HPA) system to prednisolone was evaluated by measuring serum cortisol concentration. Cortisol concentration before transplantation was 126.7 +/- 38.6 ng mL-1, while it decreased to 4.1 +/- 2.5 ng mL-1 within the period characterized by a cumulative dose of prednisolone from 300 to 700 mg. A statistically significant high incidence (P less than 0.01) of acute rejections was observed in low HPA responders; (mean cortisol concentration during prednisolone treatment exceeded 3.0 ng mL-1), 6 of 12 with a low HPA response to prednisolone showed signs of rejection, while none of the 7 with a high HPA response showed signs of rejection. The concentrations of prednisolone suppressing the in-vitro response of pretransplant lymphocytes to concanavalin A by 50% (ID50) were determined. Lymphocytes from 8 patients were extremely insensitive (ID50 greater than 500 ng mL-1), and 5 of the 8 showed signs of rejection. Lymphocytes from the other 11 patients showed high sensitivity (ID50 less than 500 ng mL-1), and only one of those showed signs of rejection. Thus, a significantly high incidence of rejection was observed in low lymphocyte-responders to prednisolone (P less than 0.05). The results suggest that an insensitive endocrine response to prednisolone correlates with an impaired lymphocyte response to the steroid, and that both of the indices are related to occurrence of rejection. Evaluation of these pharmacodynamic parameters in combination may serve as a guideline for successful immunosuppressive therapy in renal transplantation.     

Efficacy and safety of triple antihypertensive therapy with the olmesartan/amlodipine/hydrochlorothiazide combination

Background: European hypertension guidelines estimate that up to 15-20% of hypertensive patients are not controlled on a dual antihypertensive combination and require three or more different antihypertensive drug classes to achieve blood pressure (BP) control. Objective: This study in patients with moderate-to-severe hypertension assessed the efficacy and safety of adding hydrochlorothiazide (HCTZ) 12.5?mg and 25?mg to a range of olmesartan medoxomil (OLM)/amlodipine (AML) doses. Study Design: This phase III, multicentre study had a randomized, double-blind, parallel-group design that included a double-blind safety run-in and a double-blind treatment period. Intervention: Enrolled patients were screened and previous therapy was discontinued if required. During a 2-week, double-blind, safety run-in period (Weeks 0-2), patients were randomized to receive placebo, OLM/AML 20?mg/5?mg, OLM/AML 40?mg/5?mg or OLM/AML 40?mg/10?mg. During an 8-week, double-blind treatment period (Weeks 3-10), patients were allocated to eight groups depending on their initial treatment. They were either randomized to continue with the same dose of OLM/AML, or have HCTZ 12.5?mg or 25?mg added to treatment. Main Outcome Measure: The primary endpoint was formulated before data collection began. It was the change in mean diastolic BP (DBP) from baseline to Week 10 in groups with HCTZ added to OLM/AML, compared with the corresponding dual OLM/AML therapy. Results: Of 3195 patients who were screened, 2690 were randomized. Patients in every triple OLM/AML/HCTZ group had significantly greater mean reductions in DBP (p?≤?0.032 for each comparison) and systolic BP (SBP) by Week 10 (p?≤?0.0034 for each comparison), compared with patients on the corresponding OLM/AML therapy dose. The significant improvements in DBP and SBP reduction with triple OLM/AML/HCTZ therapy, compared with dual OLM/AML therapy, were observed after 4 and 6 weeks of therapy. Patients in each triple therapy group also had a significantly higher rate of BP <140/90?mmHg threshold achievement (p?≤?0.05 for each treatment comparison), compared with the dual OLM/AML groups. In three of the OLM/AML/HCTZ groups (40?mg/5?mg/25?mg, 40?mg/10?mg/12.5?mg and 40?mg/10?mg/25?mg), BP <140/90?mmHg threshold achievement by Week 10 was over 70%. Across the triple and dual combination therapy groups, treatment was well tolerated and no safety concerns for either treatment were identified. Conclusion: Adding HCTZ to a range of OLM/AML dose combinations is well tolerated and improved BP control by significantly lowering DBP and SBP and significantly increasing BP threshold achievement in patients with moderate-to-severe hypertension. Clinical Trial Registration: Registered at ClinicalTrials.gov identifier as NCT00923091.     

5-day vs. 7-day triple therapy with rabeprazole, clarithromycin and amoxicillin for Helicobacter pylori eradication

AIM: To determine whether a 5-day regimen with rabeprazole, clarithromycin and amoxicillin (RCA) was as effective as a 7-day regimen. METHODS: A total of 139 H. pylori-infected patients were randomized to receive either a 5-day or 7-day course of rabeprazole 10 mg b.d., clarithromycin 400 mg b.d. and amoxicillin 750 mg b.d. Eradication was assessed by CLO test, histology and 13C-urea breath test. RESULTS: On the intention-to-treat basis, eradication rates were 66% (46 out of 70) and 84% (58 out of 69) for the 5- and 7-day regimens, respectively (P < 0.05). Using per protocol analysis, eradication rates were 70% (46 out of 66) and 91% (58 out of 64) for the 5- and 7-day regimens, respectively (P < 0.01). Adverse events, which were observed in 14 patients from each group, caused discontinuation of treatment in only two patients, resulting in excellent compliance. CONCLUSIONS: Our 5-day regimen of RCA yielded inferior results, whereas the 7-day regimen achieved an eradication rate exceeding 90% on the per protocol basis. Therefore, treatment regimens of less than 7 days for proton pump inhibitor-clarithromycin-amoxicillin therapies cannot be recommended.