Dataset Information

Statistical analysis plan for management of hypertension and multiple risk factors to enhance cardiovascular health in Singapore: the SingHypertension pragmatic cluster randomized controlled trial.

ABSTRACT:

Introduction

Cardiovascular disease (O'Lone E, Viecelli AK, Craig JC, Tong A, Sautenet B, Herrington WG, et al., Am J Kidney Dis 76(1):109-20, 2020) remains the leading cause of death in Singapore. Uncontrolled hypertension confers the highest attributable risk of CVD and remains a significant public health issue with sub-optimal blood pressure (BP) control rates. The aim of the trial is to evaluate the effectiveness and cost-effectiveness of a multicomponent intervention (MCI) versus usual care on lowering BP among adults with uncontrolled hypertension visiting primary care clinics in Singapore. This article describes the statistical analysis plan for the primary and secondary objectives related to intervention effectiveness.

Methods

The study is a cluster randomized trial enrolling 1000 participants with uncontrolled hypertension aged ≥ 40 years from eight primary care clinics in Singapore. The unit of randomization is the clinic, with eight clusters (clinics) randomized in a 1:1 ratio to either MCI or usual care. All participants will be assessed at baseline, 12 months, and 24 months with measurements of systolic and diastolic BP, antihypertensive and statin medication use, medication adherence, physical activity level, anthropometric parameters, smoking status, and dietary habits. The primary objective of this study is to assess the effectiveness of MCI versus usual care on mean SBP at the 2-year follow-up. The primary outcome is SBP at 24 months. SBP at baseline, 12, and 24 months will be modeled at the subject level using a likelihood-based, linear mixed-effects model repeated measures (MMRM) analysis with treatment group and follow-up as fixed effects, random cluster (clinic) effects, Gaussian error distribution, and adjustment to degrees of freedom using the Satterthwaite approximation. Secondary outcomes will be analyzed using a similar modeling approach incorporating generalized techniques appropriate for the type of outcome.

Discussion

The trial will allow us to determine whether the MCI has an impact on BP and cardiovascular risk factors over a 2-year follow-up period and inform recommendations for health planners in scaling up these strategies for the benefit of society at large. A pre-specified and pre-published statistical analysis plan mitigates reporting bias and data driven approaches.

Trial registration

ClinicalTrials.gov NCT02972619 . Registered on 23 November 2016.

SUBMITTER: Allen JC

PROVIDER: S-EPMC7814171 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundHigh blood pressure (BP) is a leading contributor to cardiovascular mortality globally. There is scarcity of information on effective health systems interventions to lower BP and reduce cardiovascular risk in Southeast Asian countries. We conducted a pilot exploratory trial on 100 adults aged 40 years or older with uncontrolled hypertension to optimize the design for a structured multi-component intervention in primary care clinics for management of hypertension.MethodsTwo clinics were involved, each enrolling 50 participants, with one as the intervention clinic and the other as the control (usual care). The intervention comprised the following four components: 1) an algorithm-driven intervention using a fixed-dose combination (FDC) antihypertensive treatment and lipid lowering medication for high risk individuals, 2) subsidized FDC antihypertensive medication; 3) motivational conversation (MC) for high risk individuals; and 4) telephone follow-ups of all individuals. The process outcomes were intervention fidelity measures. The outcomes of change in parameters of interest were healthy lifestyle index (composite score of body mass index, physical activity, dietary habit, dietary quality and smoking), adherence to antihypertensive medications, and systolic and diastolic BP from baseline to follow-up at 3 months.ResultsGreater than 90 % fidelity was achieved for 3 of the 4 intervention components. Although not designed for conclusive results, the healthy lifestyle score increased by 0.16 (±0.68) with the intervention and decreased by 0.18 (±0.75) with usual care (p = 0.02). Adherence to anti-hypertensive medications at follow-up was 95.3 % in the intervention group compared to 83.8 % for usual care (p = 0.01). Systolic and diastolic BP decreased in both intervention and control groups, although statistical significance between groups was not achieved. Hypertensive individuals rated all intervention components 'highly favorable' on a Likert scale.ConclusionsOur findings indicate that the proposed, structured multi-component approach for management of hypertension is feasible for implementation in primary care clinics in Singapore, with some changes to the protocol. The observed improvement in the healthy lifestyle index and adherence to anti-hypertensive medications is promising. A large scale, adequately powered trial would be informative to assess intervention effectiveness on BP and cardiovascular risk reduction.Trial registrationThis trial has been registered at ClinicalTrials.gov. ClinicalTrials.gov number NCT02330224 . Registered on 28 December 2014.

Project description:BackgroundMajor Outcomes with Personalized Dialysate TEMPerature (MyTEMP) is a 4-year cluster-randomized clinical trial comparing the effect of using a personalized, temperature-reduced dialysate protocol versus a dialysate temperature of 36.5°C on cardiovascular-related death and hospitalization. Randomization was performed at the level of the dialysis center ("the cluster").ObjectiveThe objective is to outline the statistical analysis plan for the MyTEMP trial.DesignMyTEMP is a pragmatic, 2-arm, parallel-group, registry-based, open-label, cluster-randomized trial.SettingA total of 84 dialysis centers in Ontario, Canada.PatientsApproximately 13 500 patients will have received in-center hemodialysis at the 84 participating dialysis centers during the trial period (April 3, 2017, to March 1, 2021, with a maximum follow-up to March 31, 2021).MethodsPatient identification, baseline characteristics, and study outcomes will be obtained primarily through Ontario administrative health care databases held at ICES. Covariate-constrained randomization was used to allocate the 84 dialysis centers (1:1) to the intervention group or the control group. Centers in the intervention group used a personalized, temperature-reduced dialysate protocol, and centers in the control group used a fixed dialysate temperature of 36.5°C.OutcomesThe primary outcome is a composite of cardiovascular-related death or major cardiovascular-related hospitalization (defined as a hospital admission with myocardial infarction, congestive heart failure, or ischemic stroke) recorded in administrative health care databases. The key secondary outcome is the mean drop in intradialytic systolic blood pressure, defined as the patients' predialysis systolic blood pressure minus their nadir systolic blood pressure during the dialysis treatment. Anonymized data on patients' predialysis and intradialytic systolic blood pressure were collected at monthly intervals from each dialysis center.Analysis planThe primary analysis will follow an intent-to-treat approach. The primary outcome will be analyzed at the patient level as the hazard ratio of time-to-first event, estimated from a subdistribution hazards model. Within-center correlation will be accounted for using a robust sandwich estimator. In the primary analysis, patients' observation time will end if they experience the primary outcome, emigrate from Ontario, or die of a noncardiovascular cause (which will be treated as a competing risk event). The between-group difference in the mean drop in intradialytic systolic blood pressure obtained during the dialysis sessions throughout the trial period will be analyzed at the center level using an unadjusted random-effects linear mixed model.Trial statusThe MyTEMP trial period is April 3, 2017, to March 31, 2021. We expect to analyze and report results by 2023 once the updated data are available at ICES.Trial registrationMyTEMP is registered with the US National Institutes of Health at clincaltrials.gov (NCT02628366).Statistical analytic planVersion 1.1 June 15, 2021.

Project description:BACKGROUND:Patients with diabetes and poorly controlled hypertension are at increased risk for adverse renal and cardiovascular outcomes. Identifying these patients early and addressing modifiable risk factors is central to delaying renal complications such as diabetic kidney disease. Mobile health (mHealth), a relatively inexpensive and easily scalable technology, can facilitate patient-centered care and promote engagement in self-management, particularly for patients of lower socioeconomic status. Thus, mHealth may be a cost-effective way to deliver self-management education and support. OBJECTIVE:This feasibility study aimed to build a population management program by identifying patients with diabetes and poorly controlled hypertension who were at risk for adverse renal outcomes and evaluate a multifactorial intervention to address medication self-management. We recruited patients from a federally qualified health center (FQHC) in an underserved, diverse county in the southeastern United States. METHODS:Patients were identified via electronic health record. Inclusion criteria were age between 18 and 75 years, diagnosis of type 2 diabetes, poorly controlled hypertension over the last 12 months (mean clinic systolic blood pressure [SBP] ?140 mm Hg and/or diastolic blood pressure [DBP] ?90 mm Hg), access to a mobile phone, and ability to receive text messages and emails. The intervention consisted of monthly telephone calls for 6 months by a case manager and weekly, one-way informational text messages. Engagement was defined as the number of phone calls completed during the intervention; individuals who completed 4 or more calls were considered engaged. The primary outcome was change in SBP at the conclusion of the intervention. RESULTS:Of the 141 patients enrolled, 84.0% (118/141) of patients completed 1 or more phone calls and had follow-up SBP measurements for analysis. These patients were on average 56.9 years of age, predominately female (73/118, 61.9%), and nonwhite by self-report (103/118, 87.3%). The proportion of participants with poor baseline SBP control (50/118, 42.4%) did not change significantly at study completion (53/118, 44.9%) (P=.64). Participants who completed 4 or more phone calls (98/118, 83.1%) did not experience a statistically significant decrease in SBP when compared to those who completed fewer calls. CONCLUSION:We did not reduce uncontrolled hypertension even among the more highly engaged. However, 83% of a predominately minority and low-income population completed at least 67% of the multimodal mHealth intervention. Findings suggest that combining an automated electronic health record system to identify at-risk patients with a tailored mHealth protocol can provide education to this population. While this intervention was insufficient to effect behavioral change resulting in better hypertension control, it does suggest that this FQHC population will engage in low-cost population health applications with a potentially promising impact. TRIAL REGISTRATION:ClinicalTrials.gov NCT02418091; https://clinicaltrials.gov/ct2/show/NCT02418091 (Archived by WebCite at http://www.webcitation.org/76RBvacVU).