Abstract 2115: Results of CONTROL, a Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Study of the Effects of Tetrahydrobiopterin on Blood Pressure in Subjects with Poorly Controlled Hypertension

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Arshed Quyyumi ◽  
Susan Zieman ◽  
Emil Kakkis ◽  
John Hopkins ◽  
Martha Nicholson
Keyword(s):  
Blood Pressure ◽  
Antihypertensive Drugs ◽  
Statistical Significance ◽  
No Production ◽  
Parallel Study ◽  
Open Label ◽  
Double Blind ◽  
Lower Blood ◽  
Markers Of Oxidative Stress ◽  
Post Hoc

BACKGROUND: Tetrahydrobiopterin (6R-BH4) is a cofactor for nitric oxide (NO) synthesis. Reduced BH4 bioavailability uncouples NO synthase, decreases NO production, increases superoxide production, and may contribute to hypertension. 6R-BH4 administration has been shown to lower blood pressure (BP) and improve endothelial function in animal models and in two small, open-label clinical studies. A randomized, placebo-controlled, multicenter, parallel study was designed (‘CONTROL’) to evaluate the antihypertensive effects of 6R-BH4 in patients with treated, but poorly controlled, hypertension. METHODS: A total of 116 subjects with hypertension (SBP/DBP> 135/85) despite a stable regimen of at least two antihypertensive drugs were randomized 2:1 to oral 6R-BH4 (n=77) or placebo (n=39) and stratified by presence or absence of type 2 diabetes. Subjects received a daily dose of 10 mg/kg 6R-BH4 for 8 weeks. Endpoints were change from baseline in SBP and DBP over 8 weeks of treatment. Other measures of efficacy included change in insulin sensitivity, proteinuria, and biochemical markers of oxidative stress and NO production. RESULTS: 6R-BH4-treated subjects had a 4.4-mm Hg drop in SBP (baseline mean, 145 mm Hg) compared with a 6.4-mm Hg drop in placebo-treated subjects (baseline mean, 143 mm Hg; p=0.428). 6R-BH4-treated subjects had a 5.0-mm Hg drop in DBP (baseline mean, 90 mm Hg) compared with a 4.8-mm Hg drop in placebo-treated subjects (baseline mean, 93 mm Hg; p=0.907). No statistically significant differences in either endpoint were seen in subgroup analyses of subjects with or without diabetes, or in other measures of efficacy or safety. Post-hoc analyses in subjects with higher SBP at baseline (>150 mm Hg) showed a better SBP response to 6R-BH4 (−14.1 mm Hg) than to placebo (−5.9 mm Hg) however too few subjects with higher SBP were enrolled to reach statistical significance (6R-BH4, n=19; placebo, n=7: p=0.149). CONCLUSIONS: Oral 6R-BH4 at a dose of 10 mg/kg/day showed no anti-hypertensive effect in subjects already on a stable regimen of at least two antihypertensive drugs.

scholarly journals Use of angiotensin II receptor blockers alone and in combination with other drugs: a large clinical experience trial

2001 ◽  
Vol 2 (1_suppl) ◽  
pp. S217-S222
Author(s):  
Matthew R Weir ◽  
Rebecca Y Wang
Keyword(s):  
Blood Pressure ◽  
Essential Hypertension ◽  
Systolic Hypertension ◽  
Large Scale ◽  
Candesartan Cilexetil ◽  
Antihypertensive Drugs ◽  
Isolated Systolic Hypertension ◽  
Open Label ◽  
Background Therapy ◽  
Receptor Blockers

Angiotensin II (Ang II) receptor blockers are the newest class of antihypertensive drugs to be developed. No large-scale clinical trials have been performed to evaluate their efficacy alone, or in combination with other drugs. A large-scale, eight week, open-label, non-placebo-controlled, single-arm trial evaluated the efficacy, tolerability and dose-response of candesartan cilexetil, 16—32 mg once-daily, either as monotherapy or as part of combination therapy, in a diverse hypertensive population in actual practice settings. 6465 patients with high blood pressure, of whom 52% were female and 16% African American, with a mean age of 58 years, were included. 5446 patients had essential hypertension and 1014 patients had isolated systolic hypertension. In order to be included in this study, patients had either untreated or uncontrolled hypertension (systolic blood pressure (SBP) 140—179 mmHg and/or diastolic blood pressure (DBP) 90—109 mmHg inclusive at baseline), despite a variety of other antihypertensive drugs. Of the 5156 patients with essential hypertension and at least one post baseline efficacy measurement, the mean pretreatment blood pressure (BP) was 156/97 mmHg. Candesartan cilexetil monotherapy reduced mean SBP/DBP by 18.0/12.2 mmHg. Similarly, in the 964 patients with isolated systolic hypertension and at least one post baseline efficacy measurement, candesartan cilexetil monotherapy reduced SBP/DBP from 158/81 by 16.5/4.5 mmHg. Candesartan cilexetil was similarly effective when employed as add-on therapy. When added to baseline antihypertensive medication in 51% of the patients with essential hypertension not achieving BP control, additional reduction in BP was achieved regardless of the background therapy, including diuretics (17.8/11.7 mmHg) calcium antagonists (16.6/11.2 mmHg), beta-blockers (16.5/10.4 mmHg), angiotensin-converting enzyme inhibitors (ACE-I) (15.3/10.0 mmHg), and alpha blockers (16.4/10.4 mmHg). Likewise, when candesartan cilexetil was used as add-on therapy in patients with isolated systolic hypertension, there was a consistent further reduction of mean SBP/DBP, regardless of the background therapy. Moreover, these monotherapeutic or add-on efficacy benefits were seen regardless of age (<65 or >65 years), gender, or race. Despite the open-label design of the study which enhances efficacy owing to the placebo effect, the Ang II receptor blocker, candesartan cilexetil either alone, or as an add-on therapy, is highly effective for assisting in the control of systolic and diastolic hypertension.

Hypertension and myelosuppression as biomarkers of sunitinib efficacy in Chinese patients (pts) with metastatic renal cell carcinoma (mRCC).

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 426-426 ◽  
Author(s):  
Shukui Qin ◽  
Jie Jin ◽  
Jun Guo ◽  
Jin-Wan Wang ◽  
Fang-Jian Zhou ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Statistical Significance ◽  
Objective Response ◽  
Progression Free Survival ◽  
Chinese Patients ◽  
Rank Test ◽  
Open Label ◽  
Exact Test ◽  
Kaplan Meier ◽  
Open Label Phase

426 Background: In an open-label, phase IV study of sunitinib as 1st-line treatment (Tx) in Chinese pts with mRCC, median progression-free survival (PFS) and overall survival (OS) were 61.7 and 133.4 wk, respectively; objective response rate (ORR) was 31.1% (Ann Oncol 2012;23:851P). We retrospectively investigated correlations between on-Tx hypertension (HTN), neutropenia (N), and thrombocytopenia (T) and efficacy endpoints in pts from this trial. Methods: HTN was defined by either maximum systolic blood pressure ≥140 mm Hg (S-HTN) or maximum diastolic blood pressure ≥90 mm Hg (D-HTN). Using CTCAE assessment, N grade ≥2 and T grade >1 were used as cut-points for the analyses. Median PFS and OS were estimated by Kaplan−Meier method. The log-rank test was used to compare PFS and OS between groups with and without HTN, N grade ≥2, or T grade >1. Fisher’s exact test was used for ORR. Results: 102 pts were included in the HTN analyses, 60% with S-HTN versus 40% without S-HTN. Pts with S-HTN had greater ORR and longer PFS and OS than pts without S-HTN (Table). (Results were similar with D-HTN; see Table.) 103 pts were included in the N and T analyses, 67% with N grade ≥2 versus 33% with N grade <2, and 56% with T grade >1 versus 44% with T grade ≤1. Pts with N grade ≥2 had significantly greater ORR and significantly longer PFS and OS than pts with N grade <2 (Table). Pts with T grade >1 had greater ORR and significantly longer PFS and OS than pts with T grade ≤1 (Table). Conclusions: The developments of N grade ≥2 and T grade >1 during Tx with sunitinib were significantly associated with better outcome. Median PFS was more than twice as long for pts with S-HTN as for those without S-HTN, but the association did not reach statistical significance. [Table: see text]

Efficacy variables in patients with cancer versus patients without cancer treated with methylnaltrexone or placebo: An analysis of two placebo-controlled studies.

2018 ◽  
Vol 36 (34_suppl) ◽  
pp. 1-1
Author(s):  
Bruce Chamberlain ◽  
Michelle Rhiner ◽  
Neal E Slatkin ◽  
Nancy Stambler ◽  
Robert Joseph Israel
Keyword(s):  
Opioid Use ◽  
Advanced Illness ◽  
Open Label ◽  
Double Blind ◽  
Patients With Cancer ◽  
Pooled Data ◽  
Bowel Movements ◽  
Open Label Extension ◽  
Post Hoc ◽  
Clinical Trial Information

1 Background: A post-hoc analysis of pooled data from two randomized, double-blind studies and their open-label extensions evaluated whether baseline characteristics and efficacy endpoints differ between cancer and noncancer adults with advanced illness and opioid-induced constipation treated with methylnaltrexone (MNTX) or placebo. Methods: Patients received SC MNTX 0.15 mg/kg or placebo (study 302) and SC MNTX 8 mg (38≤62 kg), 12 mg (≥62 kg), or placebo (study 4,000) every other day for two weeks and received the same doses of MNTX as needed during the first 2 weeks of the open-label extensions. Double-blind populations were stratified by those with/without cancer. Efficacy endpoints included rescue-free bowel movements (RFBMs) within 4 hours after each dose for ≥2 of the first 4 doses; time to rescue-free laxation; rescue laxatives use; and ≥3 RFBMs/week and ≥1 RFBM/week in ≥3 of 4 weeks. Results: Median baseline opioid use (mg/day) was greater in cancer (187.9 placebo [n=114]; 180.0 MNTX [n=116]) versus noncancer patients (80.0 placebo [n=71]; 120.0 MNTX [n=62]). MNTX significantly ( P<0.0001) improved the proportion of cancer (56.9%) and noncancer (58.1%) patients with an RFBM within 4 hours after each dose for ≥ two of the first four doses versus placebo (5.3% cancer; 11.3% noncancer). Median time to laxation was significantly ( P≤0.0002) shorter in cancer (0.96 hours) and noncancer (1.25 hours) patients 24 hours after the first dose of MNTX versus placebo (22.53 and >24 hours, respectively). Rescue laxatives were used by 39.7% of cancer and 30.6% of noncancer MNTX patients versus 51.8% of cancer and 39.4% of noncancer placebo patients. Of 108 open-label extension double-blind MNTX patients, 79 (73.1%) achieved ≥3 RFBMs/week with ≥1 RFBM/week increase in ≥ three of four weeks versus 48 (46.6%) of 103 double-blind placebo patients (data from double-blind and first two weeks of open-label). Conclusions: MNTX treatment improved the laxation response, with a faster onset of laxation in patients with and without cancer, and reduced the need for rescue laxatives vs placebo. Improvements over placebo continued into the first two weeks of the open-label extensions for MNTX-treated patients. Clinical trial information: NCT00672477, NCT00402038.

scholarly journals Treatment of intraoperative hypotension with cafedrine/theodrenaline versus ephedrine

2020 ◽  
Author(s):  
L. Eberhart ◽  
◽  
G. Geldner ◽  
A. Kowark ◽  
T.-P. Zucker ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Treatment Satisfaction ◽  
Open Label ◽  
Post Hoc Analysis ◽  
Intraoperative Hypotension ◽  
Sympathomimetic Drugs ◽  
Restore Blood Pressure ◽  
Secondary Endpoints ◽  
Post Hoc

Abstract Background Sympathomimetic drugs are a therapeutic cornerstone for the management of hypotensive states like intraoperative hypotension (IOH). While cafedrine/theodrenaline (C/T) is widely used in Germany to restore blood pressure in patients with IOH, more research is required to compare its effectiveness with alternatives such as ephedrine (E) that are more commonly available internationally. Methods HYPOTENS (NCT02893241, DRKS00010740) was a prospective, national, multicenter, open-label, two-armed, non-interventional study that compared C/T with E for treatment of IOH. We describe a prospectively defined cohort of patients ≥50 years old with comorbidities undergoing general anesthesia induced with propofol and fentanyl. Primary objectives were to examine treatment precision, rapidity of onset and the ability to restore blood pressure without relevant increases in heart rate. Secondary endpoints were treatment satisfaction and the number of required additional boluses or other accompanying measures. Results A total of 1496 patients were included in the per protocol analysis. Overall, effective stabilization of blood pressure was achieved with both C/T and E. Post-hoc analysis showed that blood pressure increase from baseline was more pronounced with C/T. Fewer additional boluses or other accompanying measures were required in the C/T arm. The incidence of tachycardia was comparable between groups. Post-hoc analysis showed that E produced dose-dependent elevated heart rate values. By contrast, heart rate remained stable in patients treated with C/T. Physicians reported a higher level of treatment satisfaction with C/T, with a higher proportion of anesthetists rating treatment precision and rapidity of onset as good or very good when compared with E. Conclusion Neither drug was superior in restoring blood pressure levels; however, post-hoc analyses suggested that treatment is more goal-orientated and easier to control with C/T. Heart rate was shown to be more stable with C/T and fewer additional interventions were required to restore blood pressure, which could have contributed to the increased treatment satisfaction reported by anesthetists using C/T.

scholarly journals Empagliflozin for Patients With Presumed Resistant Hypertension: A Post Hoc Analysis of the EMPA-REG OUTCOME Trial

2020 ◽  
Author(s):  
João Pedro Ferreira ◽  
David Fitchett ◽  
Anne Pernille Ofstad ◽  
Bettina Johanna Kraus ◽  
Christoph Wanner ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Resistant Hypertension ◽  
Repeated Measures ◽  
Cox Regression ◽  
Antihypertensive Drugs ◽  
Target Organ Damage ◽  
Organ Damage ◽  
Cardiac Events ◽  
Post Hoc Analysis ◽  
Post Hoc

Abstract BACKGROUND Type 2 diabetes (T2D) and resistant hypertension often coexist, greatly increasing risk of target-organ damage and death. We explored the effects of empagliflozin in patients with and without presumed resistant hypertension (prHT) in a post hoc analysis of EMPA-REG OUTCOME (NCT01131676). METHODS Overall, 7,020 patients received empagliflozin 10, 25 mg, or placebo with median follow-up of 3.1 years. We defined baseline prHT as ≥3 classes of antihypertensive drugs including a diuretic and uncontrolled blood pressure (BP; systolic blood pressure (SBP) ≥140 and/or diastolic blood pressure ≥90 mm Hg) or ≥4 classes of antihypertensive, including a diuretic, and controlled BP. We explored the effect of empagliflozin on cardiovascular (CV) death, heart failure (HF) hospitalization, 3-point major adverse cardiac events, all-cause death, and incident/worsening nephropathy by Cox regression and BP over time by a mixed-repeated-measures-model analysis. RESULTS 1,579 (22.5%) patients had prHT. The mean difference in change in SBP from baseline to week 12 vs. placebo was −4.5 (95% confidence interval, −5.9 to −3.1) mm Hg (P &lt; 0.001) in prHT and −3.7 (−4.5, −2.9) mm Hg (P &lt; 0.001) in patients without prHT. SBP was more frequently controlled (&lt;130/80 mm Hg) with empagliflozin than with placebo. Patients with prHT had 1.5- to 2-fold greater risk of HF hospitalization, incident/worsening nephropathy, and CV death compared with those without prHT. Empagliflozin improved all outcomes in patients with and without prHT (interaction P &gt; 0.1 for all outcomes). CONCLUSIONS Empagliflozin induced a clinically relevant reduction in SBP and consistently improved all outcomes regardless of prHT status. Due to these dual effects, empagliflozin should be considered for patients with hypertension and T2D.

Abstract 6265: A Cluster Randomised Controlled Trial of Oscillometric Versus Manual Sphygmomanometers for Blood Pressure Management in Primary Care (CRAB)

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Mark R Nelson ◽  
Stephen Quinn ◽  
Linda Bowers-Ingram ◽  
Jan M Nelson ◽  
Tania M Winzenberg
Keyword(s):  
Blood Pressure ◽  
Antihypertensive Drugs ◽  
Controlled Trial ◽  
Intervention Group ◽  
Cluster Randomised Controlled Trial ◽  
Control Group ◽  
Digit Preference ◽  
Oscillometric Device ◽  
Prescribing Behaviour ◽  
Post Hoc

Although mercury sphygmomanometers are seen as the gold standard instrument for blood pressure (BP) measurement they are being withdrawn due to health and safety concerns. This has potential for changes in BP recording and management. CRAB aimed to determine the effect of an oscillometric device on digit preference, BP measurement and antihypertensive drug prescribing. Cluster randomized controlled trial in 24 family practices in Tasmania, Australia. Practices were excluded if they had oscillometric devices. Intervention practices were supplied with OMRON HEM-907 monitors for all clinical rooms and other BP measuring devices were removed. Three practices (2 control & 1 intervention) withdrew. Intervention practices had a 1 week run-in phase for familiarization and novelty reduction. Intervention practices were subsequently audited by a research nurse as prospective collection of data by a family physician may have influenced the outcome measures of interest. Control practice audit periods were matched to intervention practices. All analyses were ITT and adjusted for potential clustering. Differences in BP were analysed using generalised estimating equations. All other outcomes were analysed using multilevel mixed-effects poisson regression. Post hoc analyses were performed to determine the mediators of changes in prescribing behaviour. 3355 records were reviewed with 828 visits having BP recordings. The percentage of BP recordings ending in “0” was significantly lower in intervention vs. control practices [SBP 18% (233/329) vs. 71% (107/587), DBP 20% (229/328) vs. 70% (119/584) p<0.001]. The mean of systolic BP recordings in the intervention group was 7.5 mmHg (95% CI 5.2, 9.9 mmHg) higher than in the control group. Patients taking BP lowering drugs were more likely (IRR 1.3 95% CI 1.1, 1.7) to have a BP lowering drug prescribed if they were in the intervention compared to the control. Post hoc analyses identified systolic BP and not terminal digit preference as mediators of changes in prescribing behaviour. Oscillometric BP devices led to increases in overall prescribing of antihypertensive drugs. This was most likely mediated by reductions in measurement error leading to higher BP recordings.

scholarly journals Effects of sang-qi granules on blood pressure and endothelial dysfunction in stage I or II hypertension: study protocol for a randomized double-blind double-simulation controlled trial

Trials ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Haoyue Shi ◽  
Deshuang Yang ◽  
Jiajun Qiao ◽  
Rui Sun ◽  
Ruihan Li ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Endothelial Dysfunction ◽  
Controlled Trial ◽  
Stage I ◽  
Vascular Endothelial ◽  
Lower Blood Pressure ◽  
Double Blind ◽  
Endothelial Cell Function ◽  
Self Rating ◽  
Lower Blood

Abstract Background Worldwide, hypertension is an important public health challenge because of its high prevalence and the concomitant risks of cardiovascular disease. It induces half of the coronary heart disease and approximately two-thirds of the cerebrovascular disease burden. Vascular endothelial dysfunction has important roles in the pathophysiology of essential hypertension. Types I and II hypertension can be treated with sang-qi granules (SQG), a Chinese herbal formula. Several experimental studies on animals have shown that SQG can lower blood pressure and myocardial fibrosis by suppressing inflammatory responses. However, no standard clinical trial has confirmed this. Whether SQG can improve endothelial cell function is unknown. Methods/design In this randomized double-blind double-simulation controlled trial, 300 patients with stage I or II hypertension will be recruited and randomly allocated in a 1:1:1 ratio to group A (treatment with SQG and placebo instead of Losartan), group B (treatment with Losartan and placebo instead of SQG), and group C (treatment with SQG and Losartan). In this study, 10 g of SQG (or its placebo) will be administrated twice a day and 50 mg of Losartan (or its placebo) will be administrated once in the morning. The primary endpoint is the drug efficiency for each of the three groups. The secondary endpoints are the change in average systolic and diastolic blood pressure during the day and the night, the change in the rate at which blood pressure drops at night, assessment of target organ damage (heart rate variability, ankle–brachial pressure index, and pulse wave velocity), assessment of any improvement in symptoms (Hypertension Symptom Scale, syndrome integral scale in traditional Chinese medicine, Pittsburgh Sleep Quality Index Scale, Self-Rating Anxiety Scale, Self-Rating Depression Scale, and the 36-Item Short Form Health Survey), blood lipids, serum indicators of vascular function (changes in serum levels of ET-1, TXA2, NO, and PGI2), and safety indicators. Discussion This study aims to provide clinical evidence on the efficacy and safety of SQG in the treatment of hypertension. Moreover, the possible mechanism by which SQG may lower blood pressure will be explored by observing the protective effect of SQG on vascular endothelial function, as well as its effect on related clinical symptoms, risk factors, and the target organs of hypertension. Trial registration Chinese Clinical Trials Registry, ChiCTR1800016427. Registered on 1 June 2018.

scholarly journals High Blood Pressure Variability is an Additional Cardiovascular Risk Factor

2020 ◽  
Vol 16 (1) ◽  
pp. 94-98
Author(s):  
A. V. Rodionov
Keyword(s):  
Blood Pressure ◽  
Calcium Antagonists ◽  
Antihypertensive Drugs ◽  
Meta Analysis ◽  
Cardiovascular Complications ◽  
Cardiac Events ◽  
Important Indicator ◽  
Adverse Cardiac Events ◽  
Post Hoc

Blood pressure (BP) is a highly variable physiological indicator. Most people have BP changes within 40-50 mmHg during the day. Various external factors (from the patient’s position during BP measurement to poor adherence to therapy and abuse of short-acting antihypertensive drugs) affect the assessed indicators. Evaluation of the average daily, intra-visit, as well as long-term ("from visit to visit") BP variability is used in clinical practice. In the past twenty years a number of major studies demonstrated that increased BP variability is an independent prognostic factor that increases the risk of cardiovascular complications. The largest meta-analysis of 41 studies showed that an increase in long-term BP variability was associated with 15% and 18% increase in total and cardiovascular mortality, respectively. According to the IDHOCO project, the threshold coefficient of variation for day-today variability is >11.0/12.8. Different groups of antihypertensive drugs have an uneven effect on BP variability. Consistent data from ASCOT-BPLA, X-CELLENT and ACCOMPLISH studies indicate that among the main groups of antihypertensive drugs, calcium antagonists, mainly amlodipine, have the greatest potential for the variability reduction. A decrease in BP variability, as shown in a post-hoc analysis of CAMELOT and PREVENT studies, has a positive effect on the incidence of major adverse cardiac events (MACE). Thus, the BP variability is an important indicator that reflects the prognosis in hypertensive patients. BP variability reduction can be considered as one of the independent goals of therapy. Calcium antagonists can be considered as first-line drugs for patients with high BP variability.

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