Practice-based Clinical Trial Research Articles

Effectiveness of adhesive containing MDPB: A practice-based clinical trial.

This prospective practice-based trial assessed the longevity of composite restorations made with an adhesive containing an antibacterial monomer compared to a conventional adhesive. 9 general practices in the Netherlands were provided with two composite resin adhesives, each for a period of 9 months. Adhesive P contained the quaternary ammonium salt MDPB, and Adhesive S was a control. Patient's age and caries risk, as well as tooth type/number, reason for restoration placement, used restorative material and adhesive, and restored surfaces were recorded. All interventions carried out on these teeth in the 6 years after restoration were extracted from the electronic patient records, along with their date, type, reason, and surfaces. Two dependent variables were defined: general failure, and failure due to secondary caries. All data handling and multiple Cox regression analysis were carried out in R 4.0.5. 11 dentists from 7 practices made 10,151 restorations over a period of two years in 5102 patients. 4591 restorations were made with adhesive P, whereas 5560 were made with adhesive S. The observation period was up to 6.29 years, median observation time was 3.74 years. Cox regression showed no significant difference between the two adhesive materials when corrected for age, tooth type and caries risk, for general failure nor failure due to caries. No difference in restoration survival could be shown between composite restorations made using an adhesive containing MDPB and control. Restorations made with the adhesive containing MDPB also did not fail more or less frequently due to secondary caries. This trial is registered on clinicaltrials.gov with identifier NCT05118100.

Impact of Cost Conversations During Clinical Encounters Aided by Shared Decision-Making Tools on Medication Adherence

ObjectiveTo investigate the impact of cost conversations occurring with or without the use of encounter shared decision-making (SDM) tools in medication adherence. Patients and MethodsUsing a coding scheme that included the occurrence and characteristics of cost conversation, we analyzed a randomly selected sample of 169 video recordings of clinical encounters. These videos were obtained during the conduct of practice-based randomized clinical trials comparing care with and without SDM tools for patients with diabetes, osteoporosis, and depression. Medication adherence was described in 2 ways: as a binary (yes/no) outcome, in which the patient met at least 80% adherence, or as a continuous variable, which was the percent of days that the patient adhered to their medication. The secondary analysis took place in 2018 from trials that ran between 2007 and 2015. ResultsMost patients were White (155, 93.4%), educated (104, 63.4% completed college), middle-aged (mean age, 58 years), female (104, 61.5%), and from diabetes (86, 50.9%), depression (43, 25.4%), and osteoporosis (40, 23.7%) trials. Cost conversations occurred in 119 clinical encounters (70%) and were more frequent in those encounters in which SDM tools were used (P=.03). Furthermore, 97 (57.4%) of the participants reported more than 80% medication adherence and 70.3±29.34 percentage of days with adherent medication of 70 days. In the multiple regression model, the only factor associated with adherence (binary or continuous) was the condition of the trial in which people participated. For the participants who had cost conversations, the use of an SDM tool, their sex, the nature of cost conversation (direct or indirect), the nature of cost concerns (treatment or patient issue), and the clinician-offered strategies (yes or no) were not associated with adherence. ConclusionIn this videographic analysis of SDM practice-based clinical trials, cost conversations were not associated with the general measures of medication adherence. Future studies should assess whether a tailored cost conversation intervention would impact the cost-related nonadherence among patients.

Effectiveness of Lifestyle Intervention for Type 2 Diabetes in Primary Care: the REAL HEALTH-Diabetes Randomized Clinical Trial.

Intensive lifestyle interventions (LI) improve outcomes in obesity and type 2 diabetes but are not currently available in usual care. To compare the effectiveness and costs of two group LI programs, in-person LI and telephone conference call (telephone LI), to medical nutrition therapy (MNT) on weight loss in primary care patients with type 2 diabetes. A randomized, assessor-blinded, practice-based clinical trial in three community health centers and one hospital-based practice affiliated with a single health system. A total of 208 primary care patients with type 2 diabetes, HbA1c 6.5 to < 11.5, and BMI > 25kg/m2 (> 23kg/m2 in Asians). Dietitian-delivered in-person or telephone group LI programs with medication management or MNT referral. Primary outcome: mean percent weight change. 5% and 10% weight loss, change in HbA1c, and cost per kilogram lost. Participants' mean age was 62 (SD 10) years, 45% were male, and 77% were White, with BMI 35 (SD 5) kg/m2 and HbA1c 7.7 (SD 1.2). Seventy were assigned to in-person LI, 72 to telephone LI, and 69 to MNT. The mean percent weight loss (95% CI) at 6 and 12months was 5.6% (4.4-6.8%) and 4.6% (3.1-6.1%) for in-person LI, 4.6% (3.3-6.0%) and 4.8% (3.3-6.2%) for telephone LI, and 1.1% (0.2-2.0%) and 2.0% (0.9-3.0%) for MNT, with statistically significant differences between each LI arm and MNT (P < 0.001) but not between LI arms (P = 0.63). HbA1c improved in all participants. Compared with MNT, the incremental cost per kilogram lost was $789 for in-person LI and $1223 for telephone LI. In-person LI or telephone group LI can achieve good weight loss outcomes in primary care type 2 diabetes patients at a reasonable cost. ClinicalTrials.gov Identifier: NCT02320253.

Impact of informed consent content and length on recruitment of older adults into a community based primary prevention trial.

AimsTo compare recruitment, refusal and randomisation rates of older adults into a general practice-based clinical trial with two versions (varied format, content and language) of the Participant Information and Consent Form (PICF).MethodsThis prospective PICF study was conducted within the STAREE (STAtins in Reducing Events in the Elderly) clinical trial. Participants phone screened between October 2015 to February 2016 formed Group 1 and were mailed the extended PICF version and participants phone screened between October 2016 to February 2017 formed Group 2 and were mailed the shortened PICF version. Participants who attended a subsequent baseline screening visit were guided through a comprehensive informed consent process.ResultsDuring the screening phase of the trial, the likelihood of refusing trial participation was lower in Group 2 compared to Group 1 equating to an overall 23% reduction in risk (RR 0.77, P = 0.005, 95% CI 0.62–0.95). Group 2 had a 6.4% higher randomisation rate compared with Group 1 (65.3% versus 58.9% respectively) but this difference was not statistically significant. Factors associated with trial participation were male gender, age between 70 and 75 years and living alone (all p < .0.05).ConclusionsWhilst avoiding lengthy and complex PICF documents may assist with initial trial engagement, it needs to be supplemented with other strategies to support ongoing trial interest to randomisation and beyond. Participants refused trial participation throughout the screening phase indicating that the PICF was only one factor among several affecting an individual's decision to participate in this clinical trial.

Design and participant characteristics of a primary care adaptation of the Look AHEAD Lifestyle Intervention for weight loss in type 2 diabetes: The REAL HEALTH-diabetes study

Background/AimsThe REAL HEALTH -Diabetes Study is a practice-based clinical trial that adapted the Look AHEAD lifestyle intervention for implementation in primary care settings. The trial will compare the effectiveness and cost-effectiveness of in-person group lifestyle intervention, telephone group lifestyle intervention, and individual medical nutrition therapy (MNT), the current recommended standard of care in type 2 diabetes. The primary outcome is percent weight loss at 6 months with outcomes also measured at 12, 18, 24 (intervention completion), and 36 months. Here, we describe the adaptation, trial design, implementation strategies, and baseline characteristics of enrolled participants. MethodsThe study is a three-arm, patient-level, randomized trial conducted in three community health centers (CHCs) and one diabetes practice affiliated with one academic medical center. ResultsThe study used existing clinical infrastructure to recruit participants from study sites. Strategies for successful conduct of the trial included partnering with health-center based co-investigator clinicians, engaging primary care providers, and accommodating clinical workflows. Of 248 eligible patients who attended a screening visit, 211 enrolled, with 70 randomly assigned to in-person group lifestyle intervention, 72 to telephone group lifestyle intervention, and 69 to MNT. The cohort was 55% female, 29% non-white, with mean age 62 years and mean BMI 35 kg/m2. Enrollment rates were higher at CHC sites. ConclusionsA practice-based randomized trial of a complex behavioral lifestyle intervention for type 2 diabetes can be implemented in community health and usual clinical settings. Participant and provider engagement was higher at local CHC sites reflecting the study implementation focus.Clinical Trial Registration: NCT02320253

Changes in Caries Risk in a Practice-Based Randomized Controlled Trial.

To demonstrate that Caries Management by Risk Assessment (CAMBRA) can be successfully implemented in dental practice, 30 dentists were recruited to perform a 2-y CAMBRA trial. Twenty-one dentists (18 private practices, 3 community clinics) participated in a randomized, controlled, parallel-arm, double-blind clinical trial with individual-level assignment of 460 participants to standard of care (control) versus active CAMBRA treatment (intervention). Control or active antimicrobial and remineralizing agents were dispensed at baseline and 6-, 12-, 18-, and 24-mo recall visits according to risk level and assigned treatment arm. Primary outcome measure was dentist-determined caries risk level at recall. Among initially high-risk participants, secondary outcomes were recorded disease indicators. Generalized estimating equations were used to fit log-linear models for each outcome while accounting for repeated measurements. At 24 mo, follow-up rates were 34.3% for high-risk participants (32.1% intervention, 37.1% control) and 44.2% for low-risk participants (38.7% intervention, 49.5% control). Among 242 participants classified as high caries risk at baseline (137 intervention, 105 control), a lower percentage of participants remained at high risk in the intervention group (statistically significant at all time points). At 24 mo, 25% in the intervention group and 54% in the control group remained at high risk ( P = 0.003). Among 192 participants initially classified as low risk (93 intervention, 99 control), most participants remained at low risk. At 24 mo, 89% in the intervention group and 71% in the control group were low caries risk ( P = 0.18). The percentage of initially high-risk participants with recorded disease indicators decreased over time in both intervention and control groups, being always lower for the intervention group (statistically significant at the 12- and 18-mo time point). In this practice-based clinical trial, a significantly greater percentage of high-caries-risk participants were classified at a lower risk level after CAMBRA preventive therapies were provided. Most participants initially assessed at low caries risk stayed at low risk (ClinicalTrials.gov NCT01176396).

Understanding practice-based research participation: The differing motivations of engaged vs. non-engaged clinicians in pragmatic clinical trials.

Background/AimsPragmatic clinical trials (PCTs) represent an increasingly used strategy for “real-world” trials. Successful PCTs typically require participation of community-based practices. However, community clinicians often have limited interest or experience in clinical research. Many barriers to practice-based research have been described, but possible motivations to participate among community practices not active in research have not been well explored. The tendency is for researchers to assume similar motivations and priorities across all candidate practices. This is not necessarily the case. A better understanding of the range of reasons clinicians might see for participating in pragmatic trials could be key to promoting this type of practice-based research.MethodsSemi-structured interviews were conducted with 30 clinicians and staff members. Half of the interviewees had experience doing practice-based clinical trials and half did not. Individuals in these two groups were also diversified in terms of their practice size and location. Participants were asked about motivations and barriers to doing practice-based research in the context of a planned osteoporosis pragmatic clinical trial. Interviews were transcribed, coded, and analyzed.ResultsBarriers identified for both experienced and not-experienced clinicians and staff members included: a lack of time, increased paperwork, disruption to work flows, and concern over practice finances. Similar findings have been reported in the US, UK, Europe, and Australia. However, regarding positive motivations of practices to participate, we found systematic differences in attitude between research-engaged and research-naïve practices that have not been previously reported. The research-experienced group offered a greater number and variety of reasons to take part than the not-experienced group. While both groups expressed motivations related to patient care, clinicians and staff members experienced in practice-based clinical trials were much more likely to cite intellectual, professional, and societal benefits not envisioned by the other group.ConclusionsWe conclude that clinicians not already participating in practice-based trials may have a narrower range of motivations than those already participating. The lack of a broader view of possible benefits to participation may also translate into more obdurate recruiting challenges. These results point to the need for recruitment, engagement, and messaging approaches differentially tailored to the needs and interests of non-participating practices.

General practice-based clinical trials in Germany - a problem analysis.

BackgroundIn Germany, clinical trials and comparative effectiveness studies in primary care are still very rare, while their usefulness has been recognised in many other countries. A network of researchers from German academic general practice has explored the reasons for this discrepancy.MethodsBased on a comprehensive literature review and expert group discussions, problem analyses as well as structural and procedural prerequisites for a better implementation of clinical trials in German primary care are presented.ResultsIn Germany, basic biomedical science and technology is more reputed than clinical or health services research. Clinical trials are funded by industry or a single national programme, which is highly competitive, specialist-dominated, exclusive of pilot studies, and usually favours innovation rather than comparative effectiveness studies. Academic general practice is still not fully implemented, and existing departments are small. Most general practitioners (GPs) work in a market-based, competitive setting of small private practices, with a high case load. They have no protected time or funding for research, and mostly no research training or experience. Good Clinical Practice (GCP) training is compulsory for participation in clinical trials. The group defined three work packages to be addressed regarding clinical trials in German general practice: (1) problem analysis, and definition of (2) structural prerequisites and (3) procedural prerequisites. Structural prerequisites comprise specific support facilities for general practice-based research networks that could provide practices with a point of contact. Procedural prerequisites consist, for example, of a summary of specific relevant key measures, for example on a web platform. The platform should contain standard operating procedures (SOPs), templates, checklists and other supporting materials for researchers.ConclusionAll in all, our problem analyses revealed that a substantial number of barriers contribute to the low implementation of clinical research in German general practice. Some issues are deeply rooted in Germany’s market-based healthcare and academic systems and traditions. However, new developments may facilitate change: recent developments in the German research landscape are encouraging.

Clinical Significance of Incident Hypokalemia and Hyperkalemia in Treated Hypertensive Patients in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial

Concerns exist that diuretic-induced changes in serum potassium may have adverse effects in hypertensive patients. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial, a large practice-based clinical trial, made it possible to examine consequences of observed changes in potassium during care in conventional practice settings. Normokalemic participants randomized to chlorthalidone (C) versus amlodipine or lisinopril as a first-step drug were stratified by year-1 potassium. Postyear-1 outcomes among hypokalemics (potassium, <3.5 mmol/L) and hyperkalemics (potassium, >5.4 mmol/L) were compared with normokalemics (potassium, 3.5-5.4 mmol/L). Year-1 hypokalemia incidence was 6.8%; incidence in C (12.9%) differed from amlodipine (2.1%; P<0.001) and lisinopril (1.0%; P<0.01). Hyperkalemia incidence (2.0%) was greater in lisinopril (3.6%) than in C (1.2%; P<0.01) or amlodipine (1.9%; P<0.01). Coronary heart disease occurred in 8.1% with hypokalemia, 8.0% with normokalemia, and 11.1% with hyperkalemia. Overall, mortality was higher in hypokalemics than in normokalemics (Cox hazard ratio, 1.21 [95% CI, 1.02-1.44]) with statistically significant (interaction, P<0.01) disparity in hazard ratios for the 3 treatment arms (hazard ratios, C=1.21, amlodipine=1.60, lisinopril=3.82). Hyperkalemia was associated with increased risk of combined cardiovascular disease (hazard ratio, 1.58 [95% CI, 1.15-2.18]) without significant treatment interactions. In conventional practice settings, the uncommon appearance of hyperkalemia was associated with increased cardiovascular disease risk. Hypokalemia was associated with increased mortality; however, the statistically significant heterogeneity in hazard ratios across treatment groups strongly suggests that the observed increase in mortality is unrelated to the specific effects of C. Thus, for most patients, concerns about potassium levels should not influence the clinician's decision about initiating hypertension treatment with low-moderate doses of thiazide diuretics (12.5-25.0 mg of C).

What does it cost to establish a practice‐nurses‐led clinical trial in general practice?

To describe the processes and costs of engaging practice nurses (PNs) to establish a cluster randomised controlled trial (RCT) to study type 2 diabetes in general practice. Descriptive study of the processes and costs of engaging PNs from 59 general practices in Victoria that were participating in the Patient Engagement And Coaching for Health (PEACH) study, prior to practices being randomly assigned in the cluster RCT. Estimated direct research costs and personnel costs for establishing a general practice-based research project involving PNs (eg, costs for approaching Victorian Divisions of General Practice and the Australian Practice Nurses Association; practice and patient recruitment; research project establishment at general practices; and PNs' training, support and engagement during the study establishment period). The estimated cost to establish our PN-led general practice-based cluster RCT was over $110 000, with an average cost of $2000 per practice. Direct research and personnel costs were considerably higher than anticipated. Lack of research skills among PNs required intensive hands-on support from the research team. It is feasible to undertake a PN-led, general practice-based clinical trial in diabetes care. Future research funding needs to account for recruitment costs, including the need to build PN research capacity, and to overcome the inherent difficulties of engaging practices in complex intervention trials in primary care. International Standard Randomised Controlled Trial Number Register ISRCTN50662837.

Using Cardiovascular Age Equivalent to Close the Treatment Gap for Dyslipidemia

THE LARGE GAP IN THE QUALITY OF CARE REceived by the public 1 and what we know from clinical trials to be efficacious treatment (evidence-based clinical guidelines) has prompted the study of finding more effective methods of getting evidence into practice. 2,3 The CHECK-UP (Cardiovascular Health Evaluation to Improve Compliance and Knowledge Among Uninformed Patients) Study in this issue of the Archives 4 is an excellent example of this newly emerging discipline of implementation research. Grover et al 4 present findings from a well-designed practice-based clinical trial that tested whether providing high-risk cardiovascular patients with a cardiovascular risk profile conceptualized as an “age equivalent” along with lipid profile results improved optimal cholesterol management consistent with the 2000 Canadian Working Group on Hypercholesterolemia and Other Dyslipidemias lipid guidelines in a primary care setting. Although the intention-to-treat analysis showed a small benefit after 1 year (=�3.3 mg/dL [to convert to millimoles per liter, multiply by 0.0259] for low-density lipoprotein cholesterol between treatment arms) that reached statistical significance (P=.02), when the cardiovascular age was significantly discrepant (see Figure 3, quintiles 4 and 5, in the article by Grover et al 4 ), the percentage of patients reaching guidelinerecommended cholesterol goals increased by close to 50%. Such results, if confirmed in other studies, could have real clinical relevance. These results suggest that an informed, activated patient using an “age-equivalent risk communication strategy” as part of a patient-centered approach to cholesterol management seems to be quite effective. Other investigators 5 using a similar approach have also demonstrated promising results. Of note, the control group had major improvement in cholesterol management (�48 mg/dL in 1 year), suggesting that identifying high-risk patients not previously treated by their primary care physician led to muchimproved management. How these patients were selected was left up to each physician, but it suggests that the evaluation of unrecognized hyperlipidemic patients in the context of a clinical trial led to markedly improved management that was as or more important than the calculated coronary risk strategy used. In addition, the 4-visits-peryear paradigm used in this study was associated with a high retention rate (88%), and continued improvement in cholesterol values seems to have occurred during the entire year. Most nonpractice-based clinical trials show early improvement followed by regression to the mean. One explanation for these findings is that patients either saw the benefits of behavioral or drug therapy during the study or had high adherence to guideline recommendations that was reinforced during the 4 visits. Thus, a patient-centered, continuity-of-care model by a patient’s primary care physician seems to have been indirectly validated in this study as improving quality of care for cholesterol management, although this model was not specifically tested as part of the implementation research strategy. The results of this study are for the most part promising, but it should be pointed out that only 45% to 66% of these high-risk cardiovascular patients had reached their respective lipid targets after 1 year, and thus, a large treatment gap still persisted. More research testing the systematic identification of high-risk patients (eg, a dyslipidemia disease registry) combined with a calculated coronary risk strategy using the cardiovascular age paradigm seems to be warranted. In particular, evaluating the incremental cost-effectiveness of this strategy would be most useful.

Antihypertensive safety and efficacy and physician and patient satisfaction: results from a phase 4 practice-based clinical experience trial with diltiazem LA

This study was undertaken to assess the safety and efficacy of a new long-acting formulation of diltiazem (DLA) (Cardizem LA; Biovail Pharmaceuticals, Inc., Bridgewater, NJ) in a large heterogeneous group of hypertensive patients, and to evaluate physician and patient treatment satisfaction. In this open-label, 30-day study, physicians enrolled patients with hypertension who were to be evaluated and treated at an initial visit and at 2 follow-up visits. Data recorded for each patient included demographic information, DLA dosing strength, blood pressure (BP) readings, and adverse events (AEs). A total of 15,155 physicians completed the baseline questionnaire, and 9679 (64%) completed the final clinical evaluation questionnaire. In all, 139,965 patients with hypertension were enrolled. Initial and follow-up BP data were recorded for 50,856 (36%) of these patients. On average, systolic BP (SBP) decreased from the initial visit by 10.9 mm Hg at the first follow-up (P<.0001) and by 15.5 mm Hg at the second follow-up (mean SBP, 135.7) (P<.0001). On average, diastolic BP (DBP) decreased by 6.7 mm Hg (P<.0001) and by 9.2 mm Hg (mean DBP, 79.4) (P<.0001), respectively. The most commonly reported AEs included edema, headache, dizziness, nausea, and rash; two thirds of these events were attributed to DLA. None of the AEs attributed to DLA was reported in more than 1% of patients. Both physicians and patients expressed a high degree of satisfaction with DLA. Results from this large-scale, open-label study show that DLA was safe and produced clinically meaningful reductions in SBP and DBP; in addition, a moderate to high degree of physician and patient satisfaction was reported in a large and heterogeneous cohort of patients with hypertension.

The feasibility of a randomised, placebo-controlled clinical trial of homeopathic treatment of depression in general practice

Depression is common in general practice and lack of concordance is an important problem in its treatment. Homeopathy has few side effects and is generally associated with good compliance. We report a study investigating the feasibility of a trial to compare the effectiveness of homeopathy with a conventional antidepressant and placebo. To assess the feasibility of a general practice-based clinical trial comparing the effectiveness of individualised homeopathic treatment vs Fluoxetine (Prozac) vs placebo in the treatment of major depressive episodes of moderate severity. Randomised, double-dummy, double-blind parallel group clinical trial. Lower Clapton Group Practice, East London. Patients were recruited through their general practitioners as they presented during a 9 month period. Recruitment target was 30 patients. Eligibility was confirmed by a consultant psychiatrist using standard criteria (DSM-IV) and instruments Hamilton Depression Scale (HAMD). Suicidal and psychotic patients were excluded, additional precautions against suicide were incorporated. There was a 1 week run-in period and patients showing spontaneous improvement were excluded. Homeopathic treatment was prescribed by a GP qualified in homeopathy, from a 'limited list' of 30 homeopathic medicines, with the help of decision support software. Patients were randomised to receive verum Fluoxetine and placebo homeopathy, or verum homeopathy and placebo Fluoxetine, or placebo homeopathy and placebo Fluoxetine. Treatment duration was 12 weeks. The outcomes were: adverse drug reactions, clinical global impression (CGI); HAMD; mini international psychiatric Interview; Pittsburgh sleep quality index; Side-effects checklist; Short Form 12; treatment credibility questionnaire; work and social disability scale. The primary outcome measures were HAMD and CGI. A recruitment calculation indicated that over 230 suitable patients would be expected to attend the practice during the recruitment phase. Thirty one patients were referred for possible inclusion in the trial by their GPs. Twenty three met the entry criteria, 11 were randomised and 6 completed the study. Of the completers, one received homeopathy, 2 placebo and 3 Fluoxetine. A trial of this design in general practice is not feasible, because of recruitment difficulties, many of them linked to patient preference. Different approaches are required to recruit adequate patient numbers to trials of this sort.

Treatment of intrabony defects with enamel matrix proteins or barrier membranes: results from a multicenter practice-based clinical trial

Treatment of intrabony defects with enamel matrix proteins or barrier membranes: results from a multicenter practice-based clinical trial

The impact of managed care on gastroenterology.

Managed care has emerged out o pressures to reduce the high cost of healthcare and has brought about unprecedented change and uncertainty for the specialist. To flourish in a managed care environment the subspecialist will need to rely on strategic planning. Four emerging approached to healthcare lend themselves to strategic planning. They are 1) practice-based clinical trials, 2) outcomes research, 3) clinical practice guidelines, and 4) systems-based disease management. This report explains how subspecialists in private practice can participate in and profit from each of these new approaches.

Defining the antihypertensive properties of the angiotensin receptor blocker telmisartan by a practice-based clinical trial

Traditional randomized controlled clinical trials are designed to define the specific properties of individual antihypertensive drugs, but do not provide full information about their use in clinical practice. To evaluate the safety and efficacy of an angiotensin receptor blocker in controlling blood pressure (BP) in the community setting, this practice-based open-label study was performed by 703 practitioners in 2642 hypertensives patients. Patients were untreated at the time of study entry with BP ≥140/90 mmHg (N-1957) or were treated but uncontrolled on current monotherapy (N=−685). After stopping any previous treatment, patients received telmisartan 40 mg daily for 2 weeks; the dose was increased to 80 mg if BP remained ≥130/85 mmHg. Participants were then followed for a 4 week maintenance period. The BP fell by 18.9/12.3 mmHg in the untreated groupand by 13.1/7.9 mmHg in the previously treated but uncontrolled group. Patients not responding adequately to the 40 mg telmisartan dose had an initial BP reduction of 7.3/4.5 mmHg; titration to 80 mg gave an additional 7.5/5.0 mmHg reduction and controlled BP (<140/90 mmHg) in 44% of these patients. Overall, control occurred in 56% of white patients; 52% of black patients (who responded very well to dose up-titration); 60% of patients <65 years; and 46% in patients ≥65 (who, despite protocol requirements, were the patients least likely to get the higher dose). Thus, in contrast with randomized controlled trials using parallel group designs, this practice-based trial clearly demonstrates the value of titrating an ARB to maximal dose in patients with inadequate BP responses to the initial dose and emphasizes the benefit of structured treatment protocols in the practice setting.

Combination therapy of amlodipine/benazepril versus monotherapy of amlodipine in a practice-based setting

Background Community-based studies are conducted to determine the degree to which therapeutic interventions will succeed in real world settings. This large practice-based clinical trial assessed the efficacy and tolerability of fixed-dose combination therapy with amlodipine/benazepril, compared with amlodipine monotherapy, in patients with mild-to-moderate hypertension. Methods Hypertensive patients currently taking amlodipine were selected based on one of two criteria: inadequate blood pressure (BP) control on amlodipine (diastolic BP [DBP] ≥90 mm Hg; group 1), or inability to tolerate amlodipine (DBP ≤90 mm Hg, but with edema; group 2). Eligible patients were switched from 5 or 10 mg of amlodipine to 5/10 mg or 5/20 mg of amlodipine/benazepril for 4 weeks. In group 1 ( n = 6410), primary efficacy outcome was change in mean sitting DBP. A secondary efficacy outcome was change in mean sitting systolic BP (SBP). In group 2 ( n = 1502), primary efficacy outcome was the percentage of patients whose edema improved during therapy with amlodipine/benazepril when compared with amlodipine monotherapy. Results: In group 1, mean sitting DBP declined from 96.5 mm Hg at baseline to 84.9 mm Hg at week 4, a mean reduction of 11.5 mm Hg (95% confidence interval [CI] −11.8 to −11.3 mm Hg; P < .001). From baseline to week 4, mean sitting SBP declined from 152.9 mm Hg to 137.3 mm Hg, a mean reduction of 15.6 mm Hg (95% CI −16.0 to −15.2 mm Hg; P < .001). In group 2, 85% (95% CI 83%–87%) experienced some improvement in edema compared with baseline levels. Conclusions: Fixed-dose combination antihypertensive agent amlodipine/benazepril was safe and effective for patients who experienced either inadequate BP control or edema with amlodipine monotherapy.