Inclusion and Exclusion Criteria
The study included Pakistani nationals both male and female of age 18 years and above who were either newly diagnosed or known hypertensive patients having blood pressure of greater than ≥140 mmHg on current treatment or otherwise. Hypertensive patients with life-threatening co-morbidities were excluded such as those suffering from cardiac ailments (angina or transient ischemic attack (TIA), angiographically proven coronary disease, peripheral or cerebral vascular disease, pulmonary hypertension, having history of myocardial infarction, stroke or angioplasty / PCI or stent or high-risk conditions.
Operational Definitions
High blood pressure is defined according to International Classification of Diseases 10th revision (ICD-10)(13). According to which hypertension was classified as systolic blood pressure of greater than ≥140 mmHg and diastolic blood pressure of ≥ 90 mmHg. Blood pressure control is considered when the systolic BP is less than or equal to 140 mm Hg and the diastolic BP is less than or equal to 90 mm of Hg (37). For testing DCP3 based intervention and to enable delivery of intervention among hypertensive patients (14), the following constructs were adapted according to which intervention was modified: a) Acceptability whichreferred to the extent that stakeholders involved in qualitative research phase agreed on the use of intervention for treating hypertensive patients which included the aspect of behavioral counseling b) Appropriateness is considered as a measure of relevance of a health intervention to the disease under study and it’s perceived use among hypertensive patients c) Feasibility: The trilability of the intervention to be tested with relevance to hypertensive patients at the hospital setting. The modified intervention was pilot-tested and was externally validated by experts and was then implemented at the hospital.
Study Design & Study Population
A randomized controlled trial, double-blinded study design was used (Figure 1) to conduct this study at a single study site in which participants and physicians cannot predicted if patient will be given the intervention. The clinical trial was registered at ClinicalTrials.gov number, NCT04336631. The study was conducted at Armed Forces Institute of Cardiology & National Institute of Heart Diseases (AFIC/NIHD) in Rawalpindi city of Punjab province of Pakistan (15). The medical team of the hospital mainly composed of doctors, cardiologists, psychologist, nurses and pharmacists along with general duty staff along with research assistants who cooperated in the research data collection at the hospital. Hypertensive patients were enrolled in the trial from 1st of November 2019 till 30th of December 2019 and a registry of all study participants was created after which data collection was continued and was completed in March 2020. Patients were invited to participate in this study and were included only after obtaining their verbal and written consent for participation. No invasive procedure entailed the study and no sensitive information was collected. They were informed about the study purpose and were encouraged to participate in the research without having any direct benefits or monetary gains.
Sampling of Study Population
First 1000 hypertensive patients or patients with uncontrolled hypertension were selected through convenience-based sampling technique then after achieving stratification, a total of 240 patients were randomly allocated into intervention group and non-intervention group. Sample size was calculated using a two-tailed alpha level of p=0.05 and power of 0.80 including a non-response rate of 10%.
Ethics Approval and Consent to Participate
The study was carried out in accordance to research protocol and guidelines developed to conduct this study which involved human subjects(16). The study protocol was approved by Health Services Academy Islamabad vide letter no. 01-07/2017/PhD dated: 8th November, 2019. The materials and methods employed to conduct this study were divided into two phases. The qualitative reserach phase entailed testing DCP3 based intervention for hypertension control among hypertensive patients in the study (16). After completion of initial phase the implementing phase was carried as per the established clinical guideliens (17). The implementation phase consisted of delievering the multicomponent intervention adapted in local context among hypertensive patients.
Randomization and Intervention
For the intervention phase, hypertensive patients were screened and recruited into the trial on basis of pre-defined selection criteria. Hypertensive patients were randomized to intervention group (IG) or the usual care group (non-intervention group) in a 1:1 ratio. Participants were randomized and were stratified according to their gender and age groups of less than ≤ 30 years and more than ≥ 30 years of age (Figure 1). All study participants were approached during clinical hours and were followed up at out-patient department (OPD) of the hospital. Initial check-up of patients was carried at emergency department (ER) along with a senior physician. After physical examination of patients they were referred for blood pressure measurement and medical treatment. In emergency cases, the family members were also involved. In emergency situation, particpants were allowed to withdraw from the study only after approval from the researcher. The patients were registered into study with their CNIC / Medical Record (MR.No.) number. Approximately, 240 systematically selected hypertensive patients with uncontrolled hypertension or with systolic BP of ≥140 mmHg were invited for participation for pilot-testing. They were included in the study, and their systolic and diastolic blood pressure were measured. They were assessed for their medical history and current pharmacological therapy including necessary diagnostics tests. Randomization was achieved using random number which was generated through Microsoft excel and every 9th patient was selected in the OPD of hospital by the researcher. The intervention was only administered to patients who were randomized in the intervention group. The intervention was implemented among 240 hypertensive patients with 120 patients in intervention and usual care group. Baseline data was gathered at initial point of contact in which each patient was interviewed using a face to face interview approach. They were provided guidance for follow up at every two weeks for BP measurements, pharmacological treatment and counselling. At every follow up, they were referred to consulting physician or medical officer for their routine medical care and physical examination. The blood pressure and weight measurements were assessed at each follow up visit. Following routine medical care, patients in intervention group were provided counseling on diet, physical exercise, life style modifications. In pilot phase of the study, key messages were then formulated on basis of available evidence and qualitative research findings upon which the intervention was further modified. It was then tested for its timing and mode of delivery in OPD setting. Patients in usual care arm received routine medical care for hypertension. Patients receiving the intervention and patients in usual care arm were followed up at two weeks interval for their BP measurements. Each patient served as the unit of randomization and was assigned to either intervention or usual care group of the trial. Randomization was ensured by blinding subjects using an envelope method.
Trial Measurements
Hypertensive patients were allocated to intervention group and usual care group in a 1:1 ratio. Baseline characteristics of all study participants were recorded. The height of patients was measured using a stadiometer which was fixed by a wall in the OPD. Similarly, weight was measured using a weighing machine and body mass index (BMI) of each patient was recorded. Initially, blood pressure of each patient was measured after every 5 minutes and every patient was asked to sit in a relaxed position. It was measured using the left arm at 45 degrees for blood pressure check-up for which brachial artery was palpated. Three readings of blood pressure measurements were taken and an average of the readings were recorded. Patients were also instructed to report any adverse event to the physician and researcher. To reduce contamination, data for the study was collected at a point distant to physician’s room in the OPD department. Regular data sheets were checked for any missing information and all the data was recorded and properly maintained in SPSS version 21.
Hypertensive patients in the intervention group received a combination therapy for the management of hypertension which was based on DCP3 recommended strategies. Pharmacotherapy was provided by a physician and the intervention comprising of DCP3 interventions was administered by the researcher along with the physician in OPD. To control high blood pressure, at least two hypertensive medicines were prescribed by the physician in the treatment regimen which adhered to hypertension guidelines. Furthermore, patients were assessed at each visit for compliance to prescribed medications, lifestyle modification, stress management and changes in diet which included consumption of vegetables and a low fat food (85). The ultimate aim of the intervention was to reduce blood pressure among hypertensive patients and to improve patient’s risk factors within recommended goals established in the intervention. Patients were given awareness about hypertension only at the initial point of the study after which patients who were randomized in intervention group were counseled and were prescribed multicomponent intervention at each consecutive visit in OPD department of hospital.
Trial Outcomes
The primary outcome of the study was to achieve an overall control rate and reduction in systolic blood pressure (SBP) to recommended level of 140/90 mm Hg from baseline to three months after delivering the intervention in the intervention group. Adequate blood pressure control was assessed by taking blood pressure measurements of the patients in the intervention group and usual care group which was then compared to evaluate the effectiveness of the intervention.
Statistical Analysis
An average of blood pressure measurements was taken for each of the study participant at the baseline and follow up visits twice weekly at consecutive visits in the second and third month of enrollment of patients. Cleaning of the data was manually done prior to the analysis of the data in MS excel which was imported, coded and was entered in SPSS version 21. The test for normality was applied using Shapiro-Wilks test with a p value of ≤ 0.05 whereas; reliability was calculated which was estimated using Cronbach's alpha (p value ≤ 0.58). A minimal number of participants withdrew from the study (Figure 1) including those who were lost to follow up were excluded from the study inclusion and analysis. Descriptive statistics for sociodemographic variables were analyzed and reported in frequencies and percentages. To calculate the intervention effect, paired sample t-test was used with 95% confidence interval and p value of less than 0.05 was considered as significant (Table 3).