Achieving blood pressure control targets in hypertensive patients of rural China – A pilot randomized trial

Abstract Background This study aimed to test the feasibility and titration methods to achieve specific BP control targets in hypertensive patients of rural China. Methods A randomized, controlled, open-label trial was conducted in Rongcheng, China. We enrolled 105 hypertensive participants aged over 60 years, and who had no history of stroke and cardiovascular disease. The patients were randomly assigned to one of three systolic BP target groups: standard: 140 - < 150mmHg; moderately intensive: 130 - < 140mmHg; and intensive: <130mmHg. Patients were followed for 6 months. Discussion The optimal target for SBP lowering is still uncertain worldwide and such information is critically needed, especially in China. However, in China the rates of awareness, treatment and control are only 46.9%, 40.7% and 15.3%, respectively. It is challenging to achieve BP control in the real world and it is very important to develop population-specific BP control protocols that fully consider the population’s characteristics, such as age, sex, socio-economic status, compliance, education level and lifestyle. This randomized trial showed feasibility and safety of the titration protocol to achieve desirable SBP targets (<150, <140, and <130mmHg) in a sample of rural Chinese hypertensive patients. The three BP target groups had similar baseline characteristics. After 6 months of treatment, the mean SBP measured at an office visit was 137.2mmHg, 131.1mmHg, and 124.2mmHg in the three groups. Home BP and central aortic BP measurements were also obtained. At 6 months, home BP measurements (2 hours after drug administration) showed a mean SBP of 130.9 mmHg in the standard group, 124.9 mmHg in the moderately intense group, and 119.7 mmHg in the intensive group. No serious adverse events were recorded over the 6-month study period. Rates of adverse events including dry cough, palpitations, and arthralgia were low and showed no significant differences between the three groups. This trial gained real world experience and laid the foundation for a future large-scale BP target study.

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Achieving blood pressure control targets in hypertensive patients of rural China – A pilot randomized trial

10.21203/rs.2.12264/v2 ◽

2019 ◽

Author(s):

Xiao Huang ◽

Lishun Liu ◽

Yun Song ◽

Lan Gao ◽

Min Zhao ◽

...

Keyword(s):

Adverse Events ◽

Randomized Trial ◽

Real World ◽

Large Scale ◽

Rural China ◽

Standard Group ◽

Open Label ◽

Target Groups ◽

Serious Adverse Events ◽

Hypertensive Patients

Abstract Background This study aimed to test the feasibility and titration methods to achieve specific BP control targets in hypertensive patients of rural China. MethodsA randomized, controlled, open-label trial was conducted in Rongcheng, China. We enrolled 105 hypertensive participants aged over 60 years, and who had no history of stroke and cardiovascular disease. The patients were randomly assigned to one of three systolic BP target groups: standard: 140 - < 150mmHg; moderately intensive: 130 - < 140mmHg; and intensive: <130mmHg. Patients were followed for 6 months.DiscussionThe optimal target for SBP lowering is still uncertain worldwide and such information is critically needed, especially in China. However, in China the rates of awareness, treatment and control are only 46.9%, 40.7% and 15.3%, respectively. It is challenging to achieve BP control in the real world and it is very important to develop population-specific BP control protocols that fully consider the population’s characteristics, such as age, sex, socio-economic status, compliance, education level and lifestyle. This randomized trial showed feasibility and safety of the titration protocol to achieve desirable SBP targets (<150, <140, and <130mmHg) in a sample of rural Chinese hypertensive patients. The three BP target groups had similar baseline characteristics. After 6 months of treatment, the mean SBP measured at an office visit was 137.2mmHg, 131.1mmHg, and 124.2mmHg in the three groups. Home BP and central aortic BP measurements were also obtained. At 6 months, home BP measurements (2 hours after drug administration) showed a mean SBP of 130.9 mmHg in the standard group, 124.9 mmHg in the moderately intense group, and 119.7 mmHg in the intensive group. No serious adverse events were recorded over the 6-month study period. Rates of adverse events including dry cough, palpitations, and arthralgia were low and showed no significant differences between the three groups. This trial gained real world experience and laid the foundation for a future large-scale BP target study.

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Achieving blood pressure control targets in hypertensive patients of rural China – A pilot randomized trial

10.21203/rs.2.12264/v4 ◽

2020 ◽

Author(s):

Xiao Huang ◽

Lishun Liu ◽

Yun Song ◽

Lan Gao ◽

Min Zhao ◽

...

Keyword(s):

Blood Pressure ◽

Adverse Events ◽

Randomized Trial ◽

Blood Pressure Control ◽

Real World ◽

Rural China ◽

Pressure Control ◽

Standard Group ◽

Target Groups ◽

Hypertensive Patients

Abstract Background: This study aimed to test the feasibility and titration methods to achieve specific BP control targets in hypertensive patients of rural China. Methods: A randomized, controlled, open-label trial was conducted in Rongcheng, China. We enrolled 105 hypertensive participants aged over 60 years, and who had no history of stroke and cardiovascular disease. The patients were randomly assigned to one of three systolic BP target groups: standard: 140 - < 150mmHg; moderately intensive: 130 - < 140mmHg; and intensive: <130mmHg. Patients were followed for 6 months. Discussion: The optimal target for SBP lowering is still uncertain worldwide and such information is critically needed, especially in China. However, in China the rates of awareness, treatment and control are only 46.9%, 40.7% and 15.3%, respectively. It is challenging to achieve BP control in the real world and it is very important to develop population-specific BP control protocols that fully consider the population’s characteristics, such as age, sex, socio-economic status, compliance, education level and lifestyle. This randomized trial showed feasibility and safety of the titration protocol to achieve desirable SBP targets (<150, <140, and <130mmHg) in a sample of rural Chinese hypertensive patients. The three BP target groups had similar baseline characteristics. After 6 months of treatment, the mean SBP measured at an office visit was 137.2mmHg, 131.1mmHg, and 124.2mmHg in the three groups. Home BP and central aortic BP measurements were also obtained. At 6 months, home BP measurements (2 hours after drug administration) showed a mean SBP of 130.9 mmHg in the standard group, 124.9 mmHg in the moderately intense group, and 119.7 mmHg in the intensive group. No serious adverse events were recorded over the 6-month study period. Rates of adverse events including dry cough, palpitations, and arthralgia were low and showed no significant differences between the three groups. This trial gained real world experience and laid the foundation for a future large-scale BP target study.Trial registration: Feasibility Study of the Intensive Systolic Blood Pressure Control; ClinicalTrials.gov Identifier: NCT02817503. Registered 29 June 2016 - Retrospectively registered, https://www.clinicaltrials.gov/ct2/results?cond=&term=02817503&cntry=&state=&city=&dist=

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Achieving blood pressure control targets in hypertensive patients of rural China – A pilot randomized trial

10.21203/rs.2.12264/v1 ◽

2019 ◽

Author(s):

Xiao Huang ◽

Lishun Liu ◽

Yun Song ◽

Lan Gao ◽

Min Zhao ◽

...

Keyword(s):

Randomized Trial ◽

Large Scale ◽

Rural China ◽

Pressure Control ◽

Open Label ◽

Target Groups ◽

Hypertensive Patients ◽

Randomized Controlled ◽

Open Label Trial ◽

Titration Protocol

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Overall Tolerance and Safety of Quinapril in Clinical Trials

Angiology ◽

10.1177/000331978904000410 ◽

1989 ◽

Vol 40 (4_part_2) ◽

pp. 405-415 ◽

Cited By ~ 25

Author(s):

G.J. Frank ◽

L.E. Knapp ◽

R.W. McLain ◽

Graham J. Frank

Keyword(s):

Heart Failure ◽

Adverse Events ◽

Ace Inhibitor ◽

Comprehensive Analysis ◽

Open Label ◽

Serious Adverse Events ◽

Double Blind ◽

Hypertensive Patients ◽

High Incidence ◽

Treatment Of Hypertension

A comprehensive analysis of the reporting of adverse events, with drawals due to adverse events, and serious adverse events has been con ducted on 2,010 patients treated with quinapril hydrochloride. An analysis of all events (from both double-blind and open label studies combined) showed no increase in the incidence of events reported in congestive heart failure (CHF) patients compared to hypertensive patients. When the data for all studies were combined, an age analysis showed no increase in the total reporting of ad verse events in the 379 elderly pa tients studied. The incidence of events was lower in those patients who did not take concomitant di uretic therapy. A comparison of the double-blind phases showed quinapril to have a lower incidence of adverse events than captopril, enalapril, or chlor thalidone. An analysis of the onset of events, or withrawals, did not show an increase with time on quinapril therapy, and no dose-relationship. A review of serious adverse events did not reveal an unexpected occurrence or a high incidence of serious events considered to be related to quinapril therapy. The proportion of patients who experienced "first-dose" hypo tension, or symptomatic hypotension was similar to captopril or enalapril. Quinapril, a nonsulfhydryl ACE inhibitor, has been extensively stud ied and is equally well tolerated in the young and elderly for the treatment of hypertension and CHF.

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Comparison of Safety and Tolerability of Deutetrabenazine During Titration and Maintenance in Patients with Tardive Dyskinesia

CNS Spectrums ◽

10.1017/s1092852920002643 ◽

2021 ◽

Vol 26 (2) ◽

pp. 164-180

Author(s):

Amanda Wilhelm ◽

Karen E. Anderson ◽

Hubert H. Fernandez ◽

Hadas Barkay ◽

Nayla Chaijale ◽

...

Keyword(s):

Suicidal Ideation ◽

Adverse Events ◽

Tardive Dyskinesia ◽

Dry Mouth ◽

Fixed Dose ◽

Open Label ◽

Serious Adverse Events ◽

Open Label Extension ◽

Pharmaceutical Industries ◽

Flexible Dose

AbstractBackgroundDeutetrabenazine is approved to treat tardive dyskinesia (TD) in adults and is titrated weekly by 6 mg/day, from 12 to 48 mg/day, based on dyskinesia control and tolerability. This analysis compared the safety of deutetrabenazine during titration versus maintenance.MethodsSafety was assessed during titration versus maintenance using integrated data from two 12-week placebo-controlled studies (ARM-TD and AIM-TD) and the open-label extension study. Rates were compared for overall and serious adverse events (AEs), AEs leading to discontinuation, treatment-related AEs, common AEs (≥4%), and specific AEs (parkinsonism, suicidal ideation, akathisia, restlessness).ResultsIn titration versus maintenance, AE rates with placebo (n=130) were: overall, 43.1% vs 25.4%; serious, 4.6% vs 2.3%; leading to discontinuation, 3.1% vs 0; treatment-related, 26.9% vs 10.0%. For placebo, common AEs during titration were somnolence, headache, nausea, fatigue, and dry mouth; none occurred during maintenance. In titration versus maintenance, AE rates in fixed-dose deutetrabenazine 12–36 mg (n=216) were: overall, 33.3–38.9% vs 22.2–29.2%; serious, 2.8–6.9% vs 0–1.4%; leading to discontinuation, 2.8–5.6% vs 0; treatment-related, 8.3–16.7% vs 8.3–13.9%. For fixed-dose deutetrabenazine, common AEs during titration were headache, diarrhea, nasopharyngitis, depression, hypertension, and dry mouth; headache was the only common AE during maintenance. In titration versus maintenance, AE rates with flexible-dose deutetrabenazine (n=168) were: overall, 49.4% vs 32.7%; serious, 3.6% vs 2.4%; leading to discontinuation, 2.4% vs 0.6%. For flexible-dose deutetrabenazine, the only common AE during titration was somnolence; none occurred during maintenance. Rates of parkinsonism, suicidal ideation, akathisia, and restlessness were low and comparable in titration and maintenance.ConclusionsDeutetrabenazine was well-tolerated, with AE rates similar to placebo during both phases; AE rates were higher during titration and decreased during maintenance.FundingTeva Pharmaceutical Industries Ltd., Petach Tikva, Israel

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Allopurinol dose escalation to achieve serum urate below 6 mg/dL: an open-label extension study

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2017-211873 ◽

2017 ◽

Vol 76 (12) ◽

pp. 2065-2070 ◽

Cited By ~ 33

Author(s):

Lisa K Stamp ◽

Peter T Chapman ◽

Murray Barclay ◽

Anne Horne ◽

Christopher Frampton ◽

...

Keyword(s):

Adverse Events ◽

Dose Escalation ◽

Controlled Trial ◽

Serum Urate ◽

Extension Study ◽

Open Label ◽

Serious Adverse Events ◽

Open Label Extension ◽

Randomised Controlled ◽

Kidney Impairment

ObjectivesTo determine the long-term safety and efficacy of allopurinol dose escalation (DE) to achieve target serum urate (SU) in gout.MethodsPeople, including those with chronic kidney disease, who completed the first 12 months of a randomised controlled trial continued into a 12-month extension study. Participants randomised to continue current dose for the first 12 months began allopurinol DE at month 12 if SU was ≥6 mg/dL (control/DE). Immediate DE participants who achieved target SU maintained allopurinol dose (DE/DE). The primary endpoints were reduction in SU and adverse events (AEs) at month 24.ResultsThe mean (SE) change in SU from month 12 to 24 was −1.1 (0.2) mg/dL in control/DE and 0.1 (0.2) mg/dL in DE/DE group (p<0.001). There was a significant reduction in the percentage of individuals having a gout flare in the month prior to months 12 and 24 compared with baseline in both groups and in mean tophus size over 24 months, but no difference between randomised groups. There were similar numbers of AEs and serious adverse events between groups.ConclusionsThe majority of people with gout tolerate higher than creatinine clearance-based allopurinol dose and achieve and maintain target SU. Slow allopurinol DE may be appropriate in clinical practice even in those with kidney impairment.Trial registration numberACTRN12611000845932

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Efficacy of treatment with Ombitasvir, Paritaprevir / r + Dasabuvir over 8 versus 12 weeks in chronic HCV hepatitis genotype 1B

Romanian Journal of Infectious Diseases ◽

10.37897/rjid.2021.1.6 ◽

2021 ◽

Vol 24 (1) ◽

pp. 44-50

Author(s):

Mircea Manuc ◽

◽

Carmen Monica Preda ◽

Laura Iliescu ◽

Doina Istratescu ◽

...

Keyword(s):

Adverse Events ◽

Real World ◽

Drop Out ◽

Real World Data ◽

Serious Adverse Events ◽

Intention To Treat ◽

Genotype 1B ◽

Male Patients ◽

Severe Adverse Events ◽

Chronic Hcv

Background and aims. For the 8-week OPrD regimen, real world data are insufficient. This study aims to compare the efficacy of the two types of regimens (12-week versus 8-week) in a real world cohort of patients with genotype 1b. Material and methods. We analysed a multicentric retrospective cohort enrolling 1436 patients who started HCV therapy in 2018-2019. Liver fibrosis was staged in all subjects by Fibromax. Efficacy was assessed by the percentage of patients achieving SVR 12 weeks post-treatment (SVR12). Results. Out of the 1436 analysed patients, 112 received 8 weeks therapy and 1324 received 12 weeks. In this cohort the proportion of male patients was 25.2%, the median age 61 years, 28.2% were interferon pre-treated, and the rate of co-morbidities was 47%. 42% of the subjects had F2 fibrosis, 29% F1 fibrosis, 16% F3 and 12% F4. The SVR rate was comparable in both groups of patients (97% in those treated with OPrD 12 weeks vs 96.4% in those that received OPrD 8 weeks) (by intention-to-treat). In the 12 weeks arm, the drop-out rate was 0.8% and the rate of severe adverse events was 1%, while in the arm of 8 weeks therapy there were no severe adverse events reported and no drop-out (p = 0.25). The only predictive factor for non-response in both treatment arms was the male sex. Conclusions. OPrD 8 weeks proved to be highly efficient in our patients with a 96.4% SVR. No serious adverse events and no drop out were reported.

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Effect of Patiromer in Hyperkalemic Patients Taking and Not Taking RAAS Inhibitors

Journal of Cardiovascular Pharmacology and Therapeutics ◽

10.1177/1074248418788334 ◽

2018 ◽

Vol 23 (6) ◽

pp. 524-531 ◽

Cited By ~ 5

Author(s):

Robert A. Kloner ◽

Coleman Gross ◽

Jinwei Yuan ◽

Ansgar Conrad ◽

Pablo E. Pergola

Keyword(s):

Adverse Events ◽

Serum Potassium ◽

Common Adverse Event ◽

Open Label ◽

Serious Adverse Events ◽

End Point ◽

The Mean ◽

Baseline Characteristics ◽

Raas Inhibitors ◽

Post Hoc

Introduction: Hyperkalemia (potassium >5.0 mEq/L) affects heart failure patients with renal disease regardless of the use of renin–angiotensin–aldosterone system inhibitors (RAASi). The open-label TOURMALINE study showed that patiromer, a sodium-free, nonabsorbed potassium binder, lowers serum potassium of hyperkalemic patients similarly when given with or without food; unlike prior studies, patients were not required to be taking RAASi. We conducted post hoc analyses to provide the first report of patiromer in patients not taking RAASi. Methods: Hyperkalemic patients received patiromer, 8.4 g/d to start, adjusted to achieve and maintain serum potassium of 3.8 to 5.0 mEq/L. If taking RAASi, stable doses were required. The primary end point was the proportion of patients with serum potassium 3.8 to 5.0 mEq/L at week 3 or 4. This analysis presents data by patients taking or not taking RAASi. Results: Demographics and baseline characteristics were similar in patients taking (n = 67) and not taking RAASi (n = 45). Baseline mean (SD) serum potassium was 5.37 (0.37) mEq/L and 5.42 (0.43) mEq/L in patients taking and not taking RAASi, respectively. Mean (SD) daily patiromer doses were similar (10.7 [3.2] and 11.5 [4.0] g, respectively). The primary end point was achieved in 85% (95% confidence interval [CI]: 74-93) of patients taking RAASi and in 84% (95% CI: 71-94) of patients not taking RAASi. From baseline to week 4, the mean (SE) change in serum potassium was −0.67 (0.08) mEq/L in patients taking RAASi and −0.56 (0.10) mEq/L in patients not taking RAASi (both P < .0001 vs baseline, P = nonsignificant between groups). Adverse events were reported in 26 (39%) patients taking RAASi and 25 (54%) not taking RAASi; the most common adverse event was diarrhea (2% and 11%, respectively; no cases were severe). Five patients (2 taking RAASi) reported 6 serious adverse events; none considered related to patiromer. Conclusions: Patiromer was effective and generally well-tolerated for hyperkalemia treatment, whether or not patients were taking RAAS inhibitors.

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Abstract 19503: Durability of Antiplatelet Effect of a Novel Extended-release Formulation of Acetylsalicylic acid, Durlaza in Patients With Diabetes

Circulation ◽

10.1161/circ.132.suppl_3.19503 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Paul A Gurbel ◽

Kevin Blide P. P Bliden ◽

Jeff Patrick Patrick ◽

Katayoon Saadin Saadin ◽

Udaya Tantry

Keyword(s):

Adverse Events ◽

Extended Release ◽

Platelet Reactivity ◽

Cvd Risk ◽

Open Label ◽

Serious Adverse Events ◽

Release Formulation ◽

Antiplatelet Effect ◽

Immature Platelet Fraction ◽

Induced Aggregation

Background: High platelet turnover (HPT) is implicated in incomplete platelet inhibition and high platelet reactivity (HPR) during immediate release aspirin therapy in type II diabetes patients (T2DM). Durlaza is a new, extended-release orally administered aspirin formulation developed to provide 24-hour antithrombotic effects with once-daily dosing. Methods: In this open-label, single-center study, T2DM patients (n=40) and a history of cardiovascular disease (CVD) or multiple CVD risk factors were treated with daily 162.5 mg Durlaza for 14±4 days and adverse events were collected. Antiplatelet effects were determined by conventional aggregation (LTA), Multiplate analyzer, thrombelastography with PlateletMapping, PlateletWorks ,VerifyNow Assay, and serum thromboxane B2 (TxB2) at 1, 12, 16, and 24 hrs after the last dose. HPT was defined as immature platelet fraction of ≥3.0% or MPV≥11.0 fl. Patients exhibiting HPT and/or HPR (based on previously published cutpoints in ≥2 assays) were treated with Durlaza at 325mg for 14± 4 days and platelet function testing was repeated. Results: Prevalence of HPT and HPR was 47% and 27%, respectively. There was no loss of antiplatelet effect at 12, 16 and 24 h versus 1 h by all assays (Table 1). All patients responded to 162.5mg Durlaza as measured by arachidonic acid-induced aggregation with LTA and platelet reactivity levels were low at all timepoints (Table). Serum TxB2 was lower at 12 h (p<0.03) as compared to 1 h after 162.5mg and was lower at all times with the 325 mg vs. the 162.5 mg Durlaza (p < 0.05). HPT did not affect the PD profile of Durlaza (Pts with HPT vs. no HPT, p=NS for all). Patients had no serious adverse events and low treatment related AE rate (<5%). Conclusion: In this first comprehensive assessment, a new, extended-release 162.5 Durlaza provided sustained antiplatelet effects over 24 h in T2DM patients with a favorable safety profile. Doubling the dose further lowered serum TxB2 in pts with HPT and/or HPR.

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Abstract 14387: Dose-Related Reductions in Blood Pressure With a RNA Interference (RNAi) Therapeutic Targeting Angiotensinogen in Hypertensive Patients: Interim Results From a First-In-Human Phase 1 Study of ALN-AGT01

Circulation ◽

10.1161/circ.142.suppl_3.14387 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Stephen A Huang ◽

Jorg Taubel ◽

Giuseppe Fiore ◽

Peter Dewland ◽

George L Bakris ◽

...

Keyword(s):

Blood Pressure ◽

Single Dose ◽

Adverse Events ◽

Phase 1 ◽

Serious Adverse Events ◽

Therapeutic Targeting ◽

Dose Administration ◽

Hypertensive Patients ◽

Single Dose Administration ◽

Angiotensin Peptides

Background: Angiotensinogen (AGT) is the sole precursor of all angiotensin peptides and plays a key role in hypertension pathogenesis. We evaluated the effect of ALN-AGT01, a subcutaneous investigational RNAi therapeutic targeting hepatic AGT synthesis, on blood pressure in hypertensive patients. Methods: As part of a phase 1 program designed to assess the safety and tolerability of ALN-AGT01, we conducted a multicenter study randomizing patients aged 18-65 years with mild to moderate hypertension (mean seated systolic blood pressure [SBP] of >130 and ≤165 mmHg after washout of antihypertensive medication) 2:1 to ascending single doses of ALN-AGT01 or placebo. Change from baseline in BP at 8 weeks was measured by ambulatory BP monitoring (ABPM). We report interim results as of May 14, 2020. Results: Sixty patients (mean age 52 years, 45% female, mean baseline 24h SBP 139 +/- 7 mm Hg) were enrolled in ascending dose cohorts of 10 mg, 25 mg, 50 mg, 100 mg, or 200 mg. Dose-related reductions in serum AGT levels were observed (figure), with reductions >90% in the 100 and 200 mg dose cohorts. AGT remained durably reduced through 12 weeks after single dose administration. Concomitant reductions in BP from baseline were observed with AGT knockdown, with an over 10 mm Hg reduction of mean 24-hour SBP observed at Week 8 after single doses of 100 mg or 200 mg. No symptomatic hypotension, treatment-related serious adverse events, or clinically significant elevations in blood creatinine or potassium were seen. Conclusions: Single dose administration of ALN-AGT01 to hypertensive patients resulted in dose-related reductions in serum AGT and BP over 8 weeks without hypotension or other related serious adverse events. Durable AGT knockdown to 12 weeks supports further evaluation of once quarterly or potentially less frequent dose administration.

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