Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “RCT”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 937 records · Page 52Linked to original sources
PubMed1998

If tocolytic magnesium sulfate is associated with excess total pediatric mortality, what is its impact?

The Magnesium and Neurologic Endpoints Trial was a randomized controlled trial (RCT) done to learn whether or not receiving magnesium sulfate during preterm labor could prevent cerebral palsy. Unexpectedly, in the tocolytic arms of the trial, seven (including one set of twins) of 46 cases assigned to receive magnesium ended in total pediatric mortality (fetal + neonatal + postneonatal), compared to none of 47 cases assigned to other tocolytics ending in death. The difference between the two treatment arms is highly statistically significant (risk difference 15.2%; 95% confidence interval 4.8, 25.6; P = .006). If this relationship is confirmed by experimentation with animals or through the conduct of a large RCT at other institutions, it is possible that tocolytic magnesium will be found to be associated with the deaths of several thousand newborns in the United States annually. If the true excess total pediatric mortality is 10%, and if magnesium accounts for 40% of all tocolytics used, then tocolytic magnesium increases the absolute number of infant deaths by about 4800 every year.

Fetal Death↗
PubMed1999

An international network for evaluating neuroprotective therapy after severe birth asphyxia.

Animal studies have shown great promise in their applicability to potentially neuroprotective therapies for severe birth asphyxia in human babies. It is now necessary to consider a strategy to evaluate some or all of these techniques within the context of human neonatal randomized control trials (RCT). We have set up a pilot study for an international RCT of mature babies with severe asphyxia (defined by an Apgar score of 5 or less at 10 minutes) and have shown that we can recruit from 120 centers in 17 countries an average of three babies a week, which is the required number to undertake a study over a 2-year period with sufficient power to show a significant improvement in outcome. Particular attention must be given in future studies to the size of improvement in outcome required, generalizability of entry criteria, and the appropriate measure of functional outcome in treated babies.

Animals↗
PubMed2001

Meta-analysis comparing newer antipsychotic drugs for the treatment of schizophrenia: evaluating the indirect approach.

BACKGROUND: Meta-analysis is a useful method to assess the efficacy of newer antipsychotic drugs compared with older drugs or placebo. However, few trials directly compare novel drugs to each other. OBJECTIVE: The purpose of this study was to evaluate the method of indirect meta-analysis by applying it to data on olanzapine versus haloperidol and risperidone versus haloperidol to enable a comparison between olanzapine and risperidone. METHODS: Published randomized controlled trials (RCTs) of risperidone, olanzapine, and/or haloperidol were identified through literature searches (1983 to 1999) of the MEDLINE, Current Contents, and HealthSTAR databases and reviewed. Data for the Brief Psychiatric Rating Scale (BPRS) total score, the Positive and Negative Syndrome Scale (PANSS) negative subscale, the percentage of patients using anticholinergic drugs, and the percentage of patients dropping out due to lack of efficacy, side effects, or any cause were extracted and combined using the indirect method. These findings were compared with those from a direct comparative study of olanzapine and risperidone. RESULTS: The literature search yielded 8 RCTs comparing risperidone to haloperidol and 3 comparing olanzapine to haloperidol. Only 1 trial directly comparing olanzapine and risperidone was found. In this trial, the change in BPRS total and PANSS negative subscale scores tended to be higher with olanzapine by 1.80 and 1.10, respectively, but these differences were not statistically significant. Indirect meta-analysis yielded similar results. Changes in both BPRS total scores and PANSS negative subscale scores tended to be higher with olanzapine by 0.37 and 0.54, respectively, and again, the differences were not statistically significant. In the indirect meta-analysis, the rate of anticholinergic drug use was 19.5% greater among patients treated with risperidone than among patients treated with olanzapine (P < 0.05). In the direct comparative RCT, the rate was 13.1% higher among patients treated with risperidone (P < 0.05). The dropout rates were similar for patients treated with risperidone and those treated with olanzapine in both analyses. CONCLUSION: An indirect meta-analysis of studies comparing olanzapine with haloperidol and risperidone with haloperidol yielded conclusions similar to those found in a direct comparative RCT of olanzapine and risperidone.

Antipsychotic Agents↗
PubMedDate not supplied

Implementing a randomized clinical trial on a pediatric psychiatric inpatient unit at a children's hospital: the case of clonidine for post-traumatic stress.

Randomized clinical trials (RCTs) of psychotropic medications are uncommon among child and adolescent populations, and even rarer on pediatric, psychiatric inpatient units. We mention some of these studies, and then discuss the advantages and challenges of conducting a RCT among youngsters on an inpatient psychiatric unit in a pediatric hospital, using as an example our ongoing study of clonidine for intrusive symptoms of post-traumatic stress. Our purpose is to alert potential investigators to the obstacles they may encounter while implementing a RCT, while also pointing the way to potential resources. Advantages of inpatient units for RCTs include easy access to patients, with the potential for careful monitoring of both patients' clinical status and of medication administration. Challenges include the need for the psychiatric researcher to form liaison with other important areas within the hospital, such as the Institutional Review Board, the Pharmacy, and sometimes a General Clinical Research Center and a Clinical Research Program. The functions of these departments are discussed, and additional support for clinicians in hospital settings without these departments is described. Other issues include training clinical nurses to conduct research while making adequate provisions for their time to do so. Attitudes on a clinical psychiatric inpatient unit toward research also merit consideration. Furthermore, as with any study in a hospital setting, recruitment presents its own set of challenges. Finally, one must be cognizant of how clinical information flows between clinicians and researchers.

Child↗
PubMed1998

Altered patterns of DNA methylation on chromosomes from leukemia cell lines: identification of 5-methylcytosines by indirect immunodetection.

An immunodetection technique has been developed to map with high resolution the methylated sites of human chromosomes. We have used this method to define the methylated areas of chromosomes from normal donors and from leukemia cell lines. The chromosomes were exposed for a short time to UV light to induce mild denaturation. The methylated sites were detected in situ by using monoclonal antibodies against 5-methylcytosine (prepared in mouse), and fluorescein-conjugated antimouse immunoglobulins. The chromosomes from normal cells exhibited a fluorescent pattern with RCT banding, although some differences from previously reported patterns could be detected. With this method we have been able to show the presence of two types of R-bands: High fluorescence R-band (HFR) and low fluorescence R-band (LFR). Chromosomes from leukemia cell lines exhibited low global staining with disrupted RCT banding of the chromosomes. The decreased level of the methylation status of the chromosomes from leukemia cells was confirmed by detection of 5-methylcytosines on total immobilized DNA. Thus, we have shown that this method can be used to determine the methylated status of chromosomes and, in turn, to map not only the structural (banding) but also the functional (methylation status) properties of the different chromosome domains in normal and pathologic human cells.

5-Methylcytosine↗
PubMed1996

Making cost assessments based on RCTs more useful to decision-makers.

The appropriateness of results from economic evaluation for allocation-decisions in health care is a point of major concern for decision-makers. Much attention has been focused on potential biases stemming form the methodological shortcomings of economic evaluation. This article adds to this and concentrates on the 'real world' relevance of results from economic evaluation as an additional step towards making results more useful to decision-makers. Being the accepted standard for economic evaluation, the RCT is used as the reference case; yet, many of the issues raised are also relevant for other research designs. Three classes of biases are examined. The first relates to the limited scope that economic analysts sometimes choose in RCTs. The second class involves the methodological aspects of RCTs and questions the 'real world' relevance of the tools with which economic analysts estimate costs on the basis of RCTs. The third class concerns the representativeness of RCT results, i.e. the generalizability of these results and their usefulness in other treatment contexts. options for limiting the potential confounding influences of these biases are discussed. A check-list is provided which should be applied by decision-makers when using constructing and describing RCTs. This will enhance the relevance of the results of economic evaluation in decision-making and improve the information basis for actual allocation decisions in health care.

Cost-Benefit Analysis↗
PubMed1995

Some of David Byar's work: in appreciation.

David Byar wrote and thought with great clarity about randomized clinical trials (RCTs), pointing to their strengths--and to the limitations of alternative investigative approaches. An issue that he treated quite briefly in the seven publications that I review here is the possible gains to be had from post hoc covariate adjustment of RCT results. Calculations that I offer suggest that for realistic sample sizes and covariates of modest strength, those gains cannot be large, on average. The price to be paid for them is to replace the clear, cogent RCT paradigm with a more complex and diffuse one; this seems just cause for unease.

Biometry↗
PubMed2002

Balancing rigour and acceptability: the use of HIV incidence to evaluate a community-based randomised trial in rural Uganda.

Recent debate about the evaluation of community based, HIV/AIDS behavioural interventions has focused on the appropriateness of the randomised controlled trial (RCT) design, and the difficulty of obtaining reliable outcome measures. A community based HIV AIDS behavioural change RCT, recently conducted in rural Uganda, used HIV incidence as the principal outcome measure. This paper examines the acceptability of the trial from the community perspective. It asks whether, in a rural African setting, it is possible to implement a scientifically rigorous evaluation without compromising acceptability of the trial to the community. Opinions of the trial held by community members working as trial field workers were collected by semi-structured interview (n = 37), and focus group discussions (4) Community opinions of the trial were ascertained through 10 focus groups. For both field workers and the community, the sero-survey was more salient than the intervention, and the source of many rumours and disputes. Despite intensive mobilisation and close monitoring of field workers, it was impossible to ensure the veracity of explanations about the survey at ground level, and to protect each individual from coercion. The community expected a reward in return on their blood. Although the introduction of incentives at the final survey round increased the acceptability of the trial, they not only created jealousies and tensions, but also led to expectations of greater rewards in future. We conclude that RCTs in poor, rural communities are feasible, but the challenges involved should not be underestimated. Obtaining community support for the trial, respecting established hierarchies, and close supervision of field workers are all essential, but even then, controversies should be anticipated. There is an urgent need for relevant guidelines to help researchers navigate the complex ethical issues involved.

Acquired Immunodeficiency Syndrome↗
PubMed2004

Lay conceptions of the ethical and scientific justifications for random allocation in clinical trials.

Randomised controlled trials (RCTs) play a central role in modern medical advance, and they require participants who understand and accept the procedures involved. Published evidence suggests that RCT participants often fail to understand that treatments are allocated at random and that clinicians are in equipoise about which treatment is best. We examine background assumptions that members of the public might draw upon if invited to take part in a RCT. Four studies (N=82; 67; 67; 128), in the UK, identified whether members of the public (i). accept that an individual clinician might be genuinely unsure which of two treatments was better; (ii). judge that when there is uncertainty it is acceptable to suggest deciding at random; (iii). recognise scientific benefits of random allocation to treatment conditions in a trial. Around half the participants were loathe to accept that a clinician could be completely uncertain, and this was no different whether the context was one of individual treatment or research. Most participants found it unacceptable to suggest allocating treatment at random, though there was weak evidence that a research context may reduce the unacceptability. Participants did not judge that more certain knowledge would be gained about which treatment was best when treatments were allocated at random rather than by patient/doctor choice: scientific benefits of randomisation were apparently not recognised. Judgements were no different in non-medical contexts. Results suggest a large mismatch between the assumptions underlying the trial design, and the assumptions that lay participants can bring to bear when they try to make sense of descriptive information about randomisation and equipoise. Previous attempts to improve understanding by improving the clarity or salience of trial information, or of making explicit the research context, while helpful, may need to be supplemented with accessible explanations for random allocation.

Adult↗
PubMed1999

Generalizing from a controlled trial: the effects of patient preference versus randomization on the outcome of inpatient versus outpatient chronic pain management.

Patients accepting randomization in a randomized controlled trial (RCT) may not be representative of the clinical population from which they are drawn, calling into question the generalizability of study findings. Comparison of randomized and non-randomized inpatient and outpatient samples at baseline and in treatment outcomes up to one year was made to determine whether the findings of the RCT generalized to non-randomized patients in the same treatment program. One hundred and twenty one patients with intractable pain, randomized between inpatient, outpatient and waiting list control, were compared with 128 who elected for either inpatient or outpatient treatment. Treatment was a group-based multidisciplinary cognitive-behavioral treatment program aimed at enabling patients to return to more normal function despite persistent pain, delivered to mixed groups of randomized and elective patients, and outcome was measured by physical performance, pain impact on function, mood, and drug use. Agreement to randomization was a function of travelling distance from home to hospital. Non-randomized patients largely resembled their randomized counterparts before and after treatment. In order to indicate the clinical significance of results, analyses were conducted using numbers needed to treat (NNTs). NNTs estimate the number of patients required in the treatment condition for one of them to achieve the specified outcome who would not have achieved it in the comparison condition. Across a range of measures at one month follow-up, comparison of inpatients with outpatients gave NNTs between 2.3 and 7.5, and comparison of inpatients with waiting list controls gave NNTs between 2.3 and 3.6. At one year inpatients showed greater likelihood than outpatients of maintaining these treatment gains.

Adult↗
PubMed2000

Preoperative radiochemotherapy in locally advanced or recurrent rectal cancer: regional radiofrequency hyperthermia correlates with clinical parameters.

PURPOSE: Preoperative radiochemotherapy (RCT) is a widely used means of treatment for patients suffering from primary, locally advanced, or recurrent rectal cancer. We evaluated the efficacy of treatment due to additional application of regional hyperthermia (HRCT) to this conventional therapy regime in a Phase II study, employing the annular phased-array system BSD-2000 (SIGMA-60 applicator). The clinical results of the trial were encouraging. We investigated the relationship between a variety of thermal and clinical parameters in order to assess the adequacy of thermometry, the effectiveness of hyperthermia therapy, and its potential contribution to clinical endpoints. METHODS AND MATERIALS: A preoperative combination of radiotherapy (1.8 Gy for 5 days a week, total dose 45 Gy applied over 5 weeks) and chemotherapy (low-dose 5-fluorouracil [5-FU] plus leucovorin in the first and fourth week) was administered to 37 patients with primary rectal cancer (PRC) and 18 patients with recurrent rectal cancer (RRC). Regional hyperthermia (RHT) was applied once a week prior to the daily irradiation fraction of 1.8 Gy. Temperatures were registered along rectal catheters using Bowman thermistors. Measurement points related to the tumor were specified after estimating the section of the catheter in near contact with the tumor. Three patients with local recurrence after abdominoperineal resection, had their catheters positioned transgluteally under CT guidance, where the section of the catheter related to the tumor was estimated from the CT scans. Index temperatures (especially T(max), T(90)) averaged over time, cumulative minutes (cum min) (here for T(90) > reference temperature 40.5 degrees C), and equivalent minutes (equ min) (with respect to 43 degrees C) were derived from repetitive temperature-position scans (5- to 10-min intervals) utilizing software specially developed for this purpose on a PC platform. Using the statistical software package SPSS a careful analysis was performed, not only of the variance of thermal parameters with respect to clinical criteria such as toxicity, response, and survival but also its dependency on tumor characteristics. RESULTS: The rate of resectability (89%) and response (59%) were high for the PRC group, and a clear positive correlation existed between index temperatures (T(90)) and thermal doses (cum min T(90) >/= 40.5 degrees C). Even though the overall 5-year survival was encouraging (60%) and significantly associated with response, there was no statistically significant relationship between temperature parameters and long-term survival for this limited number of patients. However, nonresectable tumors with higher thermal parameters (especially cum min T(90) >/= 40.5 degrees C) had a tendency for better overall survival. We found even higher temperatures in patients with recurrences (T(90) = 40.7 degrees C versus T(90) = 40.2 degrees C). However, these conditions for easier heating did not involve a favorable clinical outcome, since surgical resectability (22%) and response rate (28%) for the RRC group were low. We did not notice any other dependency of thermal parameters to a specific tumor or patient characteristics. Finally, neither acute toxicity (hot spots) induced by hyperthermia or RCT nor perioperative morbidity were correlated with temperature-derived parameters. Only a higher probability for the occurrence of hot spots was found during treatment with elevated power levels. CONCLUSION: In this study with two subgroups, i.e., patients with PRC (n = 37) and RRC (n = 18), there exists a positive interrelationship between thermal parameters (such as T(90), cum min T(90) >/= 40,5 degrees C) and clinical parameters concerning effectiveness. Additional hyperthermia treatment does not seem to enhance toxicity or subacute morbidity. Procedures to measure temperatures and to derive thermal parameters, as well as the hyperthermia technique itself appear adequate enough to classify heat treatments in

Age Factors↗
PubMed1996

Prospective comparative clinical trials in The Journal of Hand Surgery (American).

All issues of The Journal of Hand Surgery (American) from volume 1, number 1 through volume 19, number 6, were reviewed to identify studies that might qualify as prospective, comparative clinical trials. Prospective studies that compared two or more clinical treatments were labeled as either randomized controlled trials (RCT) if they included some form of random assignment or controlled clinical trials (CCT) if they did not. A total of 25 CCT and 8 RCT were identified among the 3,107 articles, letters, and abstracts that were reviewed. The results will be used to update the Medline Database, to make online identification of RCTs and CCTs easier.

Controlled Clinical Trials as Topic↗
PubMed1999

Alcohol and molecular regulation of protein glycosylation and function.

Chronic alcohol exposure leads to the appearance of carbohydrate-deficient transferrin (CDT), a N-glycosylated protein and sialic acid-deficient apolipoprotein E (apoE), an O-glycosylated protein. We show that chronic ethanol treatment destabilizes sialyltransferase (ST) mRNA resulting in a concomitant decreased steady-state level of ST mRNA. As a result, alcohol markedly decreases the hepatic synthetic rate of ST. This leads to impaired sialylation of transferrin and apoE. Consequently, apoE content in plasma high-density lipoproteins (HDL) is decreased. ApoE plays a significant role in the delivery of HDL cholesterol to the liver via apo B/E receptor, a process called reverse cholesterol transport (RCT). Desialylation of apoE results in its decreased association with HDL. Thus, the dissociation constant of HDL for binding to sialo-apoE is 90 +/- 35 nM, whereas that for desialo-apoE is 1010 +/- 250 nM. More importantly, the uptake of labeled cholesterol by human HepG2 cells is decreased by 30-40% from reconstituted HDL particles (rHDL)-containing desialo-apoE compared to rHDL with sialo-apoE. We conclude that chronic alcohol exposure down-regulates the expression of sialyltransferase genes resulting in impaired sialylation of apoE. This leads to its decreased binding to plasma HDL and thereby, impairs the RCT function of HDL.

Animals↗
PubMed2002

Discrepancy between published report and actual conduct of randomized clinical trials.

Randomized clinical trial (RCT) publications with inappropriate random-sequence generation, lack of allocation concealment, or imperfect blinding yield inflated estimates of effect compared to those in which adequate methods are described. RCTs that do not state methods used yield similar effect estimates, suggesting that inadequate methods were used. We compared RCT publications with investigator reports of actual practice for 40 rheumatology RCTs published in 1997/1998. In RCTs in which these methods were not described in the trial reports and would thus have been characterized as "inadequate," investigators reported using methods of random-sequence generation and allocation concealment that would be considered adequate in 77.4 and 78.1% of RCTs, respectively. This suggests that, in contrast to previous reports, inadequate random-sequence generation and allocation concealment, per se, may not be a major problem in RCTs. Characterizing RCTs as "good" or "poor" quality based on the published report is likely to be inappropriate.

Bias↗
PubMed1998

Empirical comparison of the results of randomized controlled trials and case-control studies in evaluating the effectiveness of screening mammography.

The gold standard for evaluating screening programs is the randomized controlled trial (RCT). Case-control studies are easier to perform but their role in this area is controversial. The purpose of this article is to compare empirically the results of RCTs and case-control studies conducted to evaluate the efficacy and effectiveness of screening mammography and examine possible explanations for differences in their results. We located eight RCTs and five case-control studies of screening mammography. For women aged 40-74 years at screening, comparison of the summary risk estimates of the RCTs (0.76, 95% CI: 0.69-0.83) with that of the case-control studies (0.44, 95%, CI: 0.38-0.50) showed RCTs to have a significantly higher summary risk estimate than case-control studies (ratio = 1.74, 95% CI: 1.48-2.04). It is notable that the RCTs were compromised in most instances by low compliance rates (50-80%) in the treatment groups and by significant use of screening in the control groups (20-30%). Adjustment of the RCT results for these cross-overs yields results that are in reasonable agreement with the summary estimate for the case-control studies. These findings support the use of case-control studies to estimate the efficacy of mammographic screening where RCTs are not feasible. They suggest that the efficacy of mammography in women aged 50 years and above is somewhat greater than the effectiveness measured by the intent-to-treat analysis of RCTs.

Adult↗
PubMed1999

Are randomized control trial outcomes influenced by the inclusion of a placebo group?: a systematic review of nonsteroidal antiinflammatory drug trials for arthritis treatment.

Placebo groups are often included in randomized control trials evaluating drug therapy, yet we know little about the placebo effect. The purpose of our study was to evaluate how the presence of a placebo group in a randomized control trial (RCT) influences the patients' ratings of the efficacy of an active drug therapy and their reporting of its adverse effects. We identified studies published between 1966 and 1994 using MEDLINE. Randomized control trials evaluating acetylsalicylic acid, diclofenac, or indomethacin for the treatment of osteo or rheumatoid arthritis were included in our sample. Two investigators independently extracted data. Fifty-eight treatment arms met our inclusion criteria and were available for analysis. Twenty-five treatment arms evaluated a nonsteroidal antiinflammatory drug (NSAID) in placebo control trials and 33 in comparative trials. Using a logistic regression model to adjust for the differences between the evaluated drugs and between the types of arthritis, we found that patients receiving an NSAID in a placebo control trial were more likely to withdraw due to inefficacy (OR=1.3; 95% CI, 1.0 to 1.6; P=0.04). Using a similar model, withdrawals due to adverse effects were found to be more common when the NSAID was given in trials that did not include a placebo group (OR=1.5; 95% CI, 1.1 to 1.9; P=0.002) as were reports of cutaneous (OR=4.2; 95% CI, 1.7 to 9.9), gastrointestinal (OR=1.6; 95% CI, 1.3 to 2.0), and other types (OR=5.3; 95% CI, 3.8 to 7.4) of adverse effects. Although reports of central nervous system adverse effects were more frequent in the comparative trials, this difference was not significant. Including a placebo group in a RCT changes how patients rate the efficacy and adverse effects of their therapy. Our results highlight the need to consider the placebo effect in the design and analyses of clinical trials.

Aged↗
PubMed1999

Performing cost-effectiveness analysis by integrating randomized trial data with a comprehensive decision model: application to treatment of acute ischemic stroke.

A recent national panel on cost-effectiveness in health and medicine has recommended that cost-effectiveness analysis (CEA) of randomized controlled trials (RCTs) should reflect the effect of treatments on long-term outcomes. Because the follow-up period of RCTs tends to be relatively short, long-term implications of treatments must be assessed using other sources. We used a comprehensive simulation model of the natural history of stroke to estimate long-term outcomes after a hypothetical RCT of an acute stroke treatment. The RCT generates estimates of short-term quality-adjusted survival and cost and also the pattern of disability at the conclusion of follow-up. The simulation model incorporates the effect of disability on long-term outcomes, thus supporting a comprehensive CEA. Treatments that produce relatively modest improvements in the pattern of outcomes after ischemic stroke are likely to be cost-effective. This conclusion was robust to modifying the assumptions underlying the analysis. More effective treatments in the acute phase immediately following stroke would generate significant public health benefits, even if these treatments have a high price and result in relatively small reductions in disability. Simulation-based modeling can provide the critical link between a treatment's short-term effects and its long-term implications and can thus support comprehensive CEA.

Acute Disease↗
PubMed2000

Angiotensin II antagonists for hypertension: are there differences in efficacy?

We compared the antihypertensive efficacy of available drugs in the new angiotensin-II-antagonist (AIIA) class. The antihypertensive efficacy of losartan, valsartan, irbesartan, and candesartan was evaluated from randomized controlled trials (RCT) by performing a metaanalysis of 43 published RCT. These trials involved AIIA compared with placebo, other antihypertensive classes, and direct comparisons between AIIA. A weighted-average for diastolic and systolic blood pressure reduction with AIIA monotherapy, dose titration, and with addition of low-dose hydrochlorothiazide (HCTZ) were calculated. Weighted-average responder rates were also determined. The metaanalysis assessed a total of 11,281 patients. The absolute weighted-average reductions in diastolic (8.2 to 8.9 mm Hg) and systolic (10.4 to 11.8 mm Hg) blood pressure reductions (not placebo-corrected) for AIIA monotherapy were comparable for all AIIA. Responder rates for AIIA monotherapy were 48% to 55%. Dose titration resulted in slightly greater blood pressure reduction and an increase in responder rates to 53% to 63%. AIIA/hydrochlorothiazide combinations produced substantially greater reduction in systolic (16.1 to 20.6 mm Hg) and diastolic (9.9 to 13.6 mm Hg) blood pressure reductions than AIIA monotherapy and responder rates for AIIA/HCTZ combinations were 56% to 70%. This comprehensive analysis shows comparable antihypertensive efficacy within the AIIA class, a near-flat AIIA-dose response when titrating from starting to maximum recommended dose, and substantial potentiation of the antihypertensive effect with addition of HCTZ.

Angiotensin II↗