OBSERVATIONAL STUDIES

The CARRS – Surveillance Study: CCDC, the scientific and executive secretariat of the Center of Excellence in Cardio-metabolic Risk Reduction in South Asia (CoE-CARRS) in PHFI, is implementing a cohort modeled cardio metabolic surveillance study in three major cities in South Asia (Chennai, Delhi and Karachi). The study partners are PHFI, Emory University, AIIMS, Aga Khan University Karachi and Madras Diabetic Research Foundation, Chennai. The CARRS Surveillance study starts with a baseline cross-sectional survey enrolling 12,000 participants and following them over a period of three years to collect preliminary incidence, morbidity, and mortality data.

The broad aims of the study are:

  • To develop a model surveillance system for cardio metabolic disease (CMD) and its risk factors which can be adopted for continuing surveillance both within and across countries in South Asia
  • To measure the incidence of CMD risk factors and disease events, as well as the associated morbidity and mortality The baseline survey of the CARRS-Surveillance study has been completed. The follow up has begun in all three sites. In Delhi, first year follow up is complete with more than 90% response rate.

CARRS – Sub-Studies

1. Oral health, habits and risk factors in urban India: The sub study was initiated in November 2014 with the overall goal of developing and integrating an oral health component into the established CARRS Surveillance system. The main objectives of the study are to i) Assess the prevalence of oral diseases and its associated risk factors in urban India, ii) Study the oral hygiene practices, and iii) Study the relationship between oral manifestations and diabetes. The study would include a total of 1970 participants from Delhi site of the CARRS cohort II. Data is being captured using an electronic data collection tool based on the lines of “WHO STEP wise” approach which includes both questionnaire and clinical examination. Clinical examination is being conducted by trained dentists.

2. CARRS- GIS study: The CARRS- GIS study aims to study the relationship between built environment (built environment encompasses places and spaces created or modified by people including buildings, parks, and transportation systems) and Cardiometabolic (concerning both heart disease and metabolic disorders such as diabetes) risk factors (Smoking, low physical activity, obesity etc) in South Asia. An understanding of the relationship between built environment and disease would give us deeper insights into the societal and environmental determinants of disease. Such knowledge is crucial in initiating control measures.
The study is part of the Center for Cardiometabolic Risk Reduction in South Asia (CARRS) Surveillance study, a collaborative effort between CCDC, Public Health Foundation of India (PHFI), All India Institute of Medical Sciences (AIIMS), Aga Khan University, Karachi, Madras Diabetes Research Foundation, Chennai and Emory University, Atlanta, USA. Dr D Prabhkaran, Executive Director, CCDC is the principal investigator of the study funded by National Institute of Health, USA.
The CARRS-GIS study links the health and demographic details of the CARRS study participants in New Delhi, Chennai and Karachi with their neighbourhood environment. This is done by obtaining the location details of study households and neighbourhood landmarks such as health facilities, fast foods, alcohol outlets etc using portable GPS receivers and integrating it into a Geographic Information System (GIS) linked with Geo referenced satellite images of the neighbourhood locations obtained from Google earth.
The study will help us to identify hot and low spots of diseases and risk factors and scientifically assess the relationship between built environment features like play grounds and parks with chronic diseases and risk factors in the South Asian setting. This can help in introducing locally targeted public health interventions and design healthier living spaces.

Developing the Evidence Base for a National Salt Reduction Programme for India:This is a three year project designed to inform the development of a national strategy for salt reduction in India. Study partners are the George Institute for Global Health and Centre for Chronic Disease Control. The objective of the study is to conduct an integrated, multifaceted research programme compromised of stakeholders assessments, population surveys and food supply evaluations that will provide the baseline data required to inform development of a national strategy for salt reduction in India. Population surveys was done in Delhi (North India, Urban), Faridabad (North India, Rural), Hyderabad (South India, Urban) and East and West Godavari districts in Andhra Pradesh (South India, Rural).
Funding agency: National Health and Medical Research Council (NHMRC), Australia.

Management of Acute Coronary Events (MACE) Registry: An up to date registry data on acute coronary syndrome (ACS) is required in India to incorporate evidence-based medicine in treatment and to gather information on long term outcomes of patients. This will lead to an efficient coordination of ACS prevention, treatment and rehabilitation. The MACE registry study is funded by ICMR and coordinated by CCDC and St. John’s Medical College, Bangalore. This feasibility study aims to provide a framework for data collection which may provide cost effective strategies to reduce the burden of ACS, as well as provide country specific optimal management strategies to reduce mortality due to ACS. It is expected that initiation of MACE Registry at multiple sites in the country will contribute towards improving the understanding of ACS patient characteristics and establishing country specific guidelines for management of ACS. CCDC trained the participating centres and also helped develop the web module.
Funding agency: Indian Council of Medical Research (ICMR)

The Acute Coronary Syndrome Quality Improvement in Kerala (ACS QUIK):The Acute Coronary Syndrome Quality Improvement in Kerala (ACS QUIK) study is a cluster randomized, stepped wedge clinical trial assessing implementation and effect of a locally-developed quality improvement toolkit for patients with ACS in Kerala, India. Participating hospitals are randomly assigned to one of five steps. Every four months, a new step implements a quality improvement toolkit. Those hospitals continue to use the quality improvement toolkit through the end of the trial for all ACS patients. The aim of this study is to evaluate, in comparison to usual care, the effect of a locally-developed, evidence-based health care quality improvement toolkit on 30-day major adverse cardiovascular events (MACE). The primary outcome is 30-day major adverse cardiovascular events (MACE) rates, defined as death, myocardial infarction, stroke, and major bleeding defined by GUSTO criteria.

GENETIC RESEARCH

Genomics of lipids and BP in Indians: Genome-wide association studies (GWAS) have found several potential genetic markers for lipids but mainly in the European population. To the best of our knowledge, these findings are not validated in the Indian population living in India. We therefore propose to validate the most significant findings of GWAS on triglycerides and HDL-c in the Indian population. The objectives of the study are: 1) to validate the most relevant findings of GWAS in triglycerides and HDL-c in the Indian population and 2) to test whether environment modifies the genotype-phenotype association by studying rural and urban cohorts. We will use 1500 urban and rural samples randomly selected from Delhi and rural Haryana and will identify top independent signals of lipid traits (triglycerides and HDL-c) from the published GWAS literature.. In total, a panel of 30 SNPs will be generated. The DNA samples will be utilized to genotype these 30 SNPs on SEQUENOM platform.
Funding Agency: Indian Council of Scientific and Industrial Research

CLINICAL TRIALS & TRANSLATIONAL RESEARCH

Yoga-CaRe trial: Yoga-CaRe trial is one of the largest cardiac rehabilitation trials assessing the effects of a yoga based cardiac rehabilitation programme on cardiovascular morbidity and mortality in patients following acute myocardial Infarction. The study is a funded through a prestigious Indo-UK collaborative grant sponsored through ICMR, India and MRC, UK and is being conducted in 25 sites across India on a total of 4000 participants The primary outcomes of the trial are the cardiovascular events (Composite of all-cause mortality, non-fatal myocardial infarction, non-fatal stroke) and the patient’s quality of life. The trial duration is 2 years with a median follow-up of 12 months for each participant and the participants will be recruited till last 6 months.

Developing and Testing Integrated, Multi-factorial Cardiovascular Disease Risk Reduction Strategies in South Asia (CARRS Translation Trial): The CARRS Translation Trial is a multi-site, individually randomized, controlled translation trial of a cardiovascular risk reduction intervention in 1,146 Type 2 diabetes patients attending 7 established out-patient clinics in South Asia, for a mean follow-up of 30 months. Half of the patients were randomized to the intervention, which utilizes a combination of health care management strategies: (1) a web-enhanced decision-support software that serves to store patient health records; provide patient management advice; and prompt and remind care providers and participants of recommended care processes; and (2) a non-physician care coordinator to facilitate patient self-management and provider adherence to evidence-based management guidelines, which includes regular 3-monthly visits for patient evaluation. The care coordinator is the main person who interacts with the decision-support software, collecting and inputting all intervention data into the decision support software and providing management prompts to the study physician. The control group received the standard care existing at the clinical site. All study physicians have equal access to the evidence-based management guidelines.

CABG Off or On Pump Revascularization Study (CORONARY): The use of Coronary-Artery Bypass Grafting (CABG) as a common procedure in reducing mortality in patients with serious coronary artery disease is well-established. On-pump CABG, which uses a cardiopulmonary bypass pump, is the most common form of this procedure but has been associated with cardiovascular complications. Because many of the complications stem from the use of the pump itself, Off-pump CABG techniques were developed in order to improve patient outcomes.

The CABG off or On Pump Revascularization Study (CORONARY) is the largest, randomized-controlled surgical trial to date that was designed to evaluate the safety and long-term outcomes of CABG patient who underwent either off-pump or on-pump surgery. The trial is funded by Canadian Institute for Health Research and centrally coordinated by the Population Health Research Institute based at the Mc Master University, Canada (CORONARY ClinicalTrials.gov number, NCT00463294.). The primary objective of the study is to determine whether off-pump CABG surgery compared to on-pump CABG surgery reduces major clinical vascular events in the short term (30 days) and whether the benefits are maintained at long term (5 years) in patients undergoing isolated CABG surgery. The trial has recruited 4700 patients worldwide and 1307 participants were recruited from India. The study has a planned follow-up of at least 5 years. At 1-year, no significant difference was observed between either methods of CABG surgery in the primary composite outcome. Also, the CORONARY trial demonstrated that off-pump CABG was clinically as safe and effective as on-pump with no difference in costs. Thus the decision as to which method to choose is free from costs restraints and should be based on patient preference and surgeon expertise. The long term participant’s follow-up is currently on-going and final study visits are scheduled to complete by October 2015. As of July 2015, the study has completed 28.66% of final visits!

Surgical Treatment for Ischaemic Heart Failure (STICHES) Trial: The STICH Trial completed enrolment of 1,212 subjects, which included 168 subjects randomized in India, in whom the responsible physicians were at equipoise regarding the benefits of myocardial revascularization in May 2007. Patients were randomized 1:1 to continuing optimal medical therapy (MED) with or without Coronary Artery Bypass Graft (CABG) to test whether CABG leads to the hypothesized mortality reduction of 25% over MED at an average of 5 years. Duke Clinical Research Institute is the coordinating centre for this study. The STITCHES Trial is an extension of the STITCH Trial, taking advantage of the opportunities that the surviving STICH patients will be followed for an additional 5 years in a minimal risk, registry type study with the following specific aims:

  • To determine whether CABG with medical therapy (MED) improves 10-year survival compared to MED alone and how treatment-related outcome differences seen at 5 years vary over time.
  • To determine whether CABG with MED leads to differences in health outcomes including functional status and symptoms compared to MED alone at 10 years among important subgroups defined by baseline clinical status, symptoms, coronary anatomy, functional status, non-invasive measures of myocardial ischemia and viability and/or genotype.
  • To quantify the relative, incremental predictive value of baseline non-invasive cardiac imaging on long-term treatment-dependent results (relative to the short and intermediate-term).
  • To determine whether CABG with MED leads to changes in cardiac morphology, function and hemodynamics over time (4 and 24 months) compared to MED alone and to define how these changes relate to 10 year health outcomes.
    Funding Agency: National Heart, Lung, and Blood Institute

DISHA Study (Diet and lifestyle InterventionS for Hypertension Risk reduction through Anganwadi Workers and Accredited Social Health Activists): This ICMR-funded multi-centre cluster randomised controlled trial aims to assess the effectiveness of diet and lifestyle intervention through Information Education Communication (IEC) tools with Angan Wadi Centres (AWCs) as the centre of knowledge dissemination for Non-communicable Disease risk reduction. The secondary objectives of the study are i) to assess the operational feasibility of integrating NCD risk reduction in community health programs through existing community level healthcare volunteers such as ASHA or equivalent, ii) to assess the usefulness of trained healthcare workers to affect changes in dietary fat, fibre and salt, tobacco and alcohol consumption and increasing physical activity iii) To assess the efficacy of these interventions to evaluate changes in lipid levels and glycemia.

DEMONSTRATION PROJECTS

The m-Power Heart Project: The m-Power Heart Project, supported by the Medtronic Foundation, USA is being implemented in the Solan District of Himachal Pradesh. The project involves three specific activities; 1) to deploy trained community health workers (CHWs) for improving the access to CVD care at the community level, 2) to integrate software based decision support systems (DSS) to aid physicians and CHWs in practicing evidence based medicine for CVDs/diabetes in order to improve the quality of care and 3) to develop a CVD/diabetes e-learning package for training primary health care professionals aimed at building capacity for high-quality CVD care in India. The project will be operational in 36 sub centres of 4 CHCs, 1 civil hospital and one district hospital. Evidence based management algorithms will help physicians and health workers evaluate the clinical condition of people with CVDs/diabetes presented at primary care settings.
Funding Agency: Medtronic Foundation

COLLABORATIVE PROJECTS

mWELLCARE – An integrated mHealth system for the prevention and care of chronic conditions: Public Health Foundation of India leads the mWellcare trial, along with multiple partners. The study aims to develop affordable technologies for the detection and management of diabetes, hypertension and depression at primary care settings in India. As part of this project, we plan to develop a smartphone application for use at primary care settings to enable the health care team deliver high quality care at the public health facilities. This trial will evaluate effectiveness of the smartphone tool in reduction on mean blood pressure and blood sugar level among hypertension/ diabetes patients. The project is being implemented in Haryana and Tamil Nadu. In the intervention health facilities, the health care team would be able to treat hypertension/diabetes patients using the smartphone tool, whereas, the control group health facilities would follow standard care as suggested by the national guidelines issued by the government of India. The effect of the intervention will be assessed at twelve months comparing the difference in blood pressure and blood glucose among patients in both groups.
Funding Agency: Wellcome Trust

CAPACITY BUILDING

Research capacity building and establishment of networks in 24 developing countries: CCDC functions as the Scientific Secretariat of the Initiative for cardiovascular health research in the developing countries (ICHealth). IC-Health aims to promote health research that will enable the early integration of cost-effective interventions for cardiovascular risk reduction in populations as well as in individuals at high risk of CVD, into primary health care settings of low and middle-income countries (LICs and LMICs). The research facilitation initiative of the IC-Health is being managed by CCDC through an innovative funding programme starting with identification of research priorities through workshops involving experts and scientists from developing and developed countries. Based on identified research priorities, grants are awarded to developing country investigators for both developing research proposals ($10,000) as well as larger project start-up grants ($50000). This research facilitation process, involving technical support of experts of developed countries, have resulted in some developing country researchers independently developing and applying for large project grants through the seed grant provided by IC-HEALTH. The major output of this research facilitation process, led by CCDC, has been the establishment of a network of researchers in 24 developing countries, enhancing the research capacity for CVD health research in these nations.
Funded by: Global forum in health research and World Bank.

Fogarty International Clinical Research Training Site: CCDC serves as an implementing partner for the Fogarty International Clinical Research Training Site at PHFI. Every year we host 1-2 Fogarty International Clinical Research Scholars and 1 Fogarty Fellow in a twinning plan in which the Indian Scholar is also fully supported for their training including research grants. This is a highly successful program with most fellows/ scholars publishing in peer reviewed journals as well as obtaining career grants such as the prestigious NIH career development (“K”) awards.