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Clinical Studies Support

  

Background

Clinical studies support Core will provide support for translational and clinical studies recruiting subjects across the CG Research Themes at NHCS. It aims to attract external funding from academic collaborators and industry-sponsored clinical studies.

The Key Functions:

  • To provide supplementary CRC support for recruitment of subjects by research theme PIs who undertake clinical research studies.
  • To provide clinical study oversight and management in terms of;

    • Applying for regulatory (HSA) and ethics (IRB) approvals
    • Maintaining source documents and proper housekeeping
    • Adverse event reporting and compliance with all safety guidelines
    • Close monitoring and follow up of subjects according to study design/protocol

    • Facilitate study closure

     Clin Assoc Prof David Sim.png  Clin Assoc Prof David Sim.png  salma.jpg  wan shan.jpg

       Clin Assoc Prof David Sim           Miss Florence Ang                   Miss Salma Asali                    Miss Leow Wanshan   

    Expertise

    CTRO1.jpg

    This core will support research themes and integrate with other cores:

    • Recruitment of healthy subjects and cardiometabolic diseases patients needed for Advanced Cardiometabolic Imaging Core (#3), Diabetes and Heart failure theme (#3).
    • Collection of blood samples from healthy subjects and cardiometabolic diseases patients for metabolomics analysis by the Genomics and Metabolomics Core (#4).

          • Collection of blood samples to generate iPSCs from healthy subjects and cardiometabolic disease patients for Cardiometabolic Disease models Core (#2), Heart Protection theme (#2), Diabetes and Heart failure theme (#3).
          • Recruit patients for EA-CABG study to investigate whether electro-acupuncture is cardioprotective in cardiac surgery patients Heart Protection theme (#2).


                Methodology

                Our core is supported by a team of management staff and senior/clinical research coordinators. We function as a team to operate and coordinate clinical research projects to ensure smooth operation of the projects are conducted in accordance to good clinical practice.

                Our management team assist PIs in grant applications, budget planning and tracking of regulatory/ethics approval status. We worked closely with external vendors in negotiating contract agreements, budget costing as well as managing their expectations and milestones accordingly. We monitor the progress of the project and communicate regularly with all stakeholders to ensure successful completion of the project. We provide supervision, guidance and training as needed to all staff to execute and meet the projects standard accordingly.

                The coordinators play a vital role in managing the projects to ensure study compliance and strict adherence to good clinical practices. They communicate regularly with external monitors for projects initiation, protocol and recruitment matters, data queries resolution, safety reporting and project completion. They assist the PI in all the projects related follow-up visits (clinic or phone contact) and all research administrative matters including compiling and generating clinical study reports, annual study report for all projects to CIRB, grant authority if applicable.


                Research Area

                Our core provides expertise and manpower support to various industry sponsored clinical trials and Investigator-Initiated research studies. Some are of significant importance and impactful which includes but not limit to the following:

                1. A multi-national and multicenter trial comparing the effect of intravenous ferric carboxymaltose on hospitalizations and mortality in iron-deficient patients admitted for acute heart failure. The research findings have been translated into clinical practice in NHCS and benefits heart failure patients so that they can lead better life and reduce re-admission to hospitals.

                2. A 3-year, SG$6million program (APOLLO study) designed to build an AI-driven CT Coronary Angiography platform for automated anonymization, reporting, Agatston scoring and plaque quantification in CAD. It is a "one-stop" platform spanning from diagnosis to clinical, management and prognosis, and aid in predicting therapy response in the pharmaceutical industries.

                3. A longitudinal study, known as the Cardiac Ageing study, began in 2014 and involved more than 1000 participants.
                  It aimed to study the characteristics of how the heart ages, in both structure and function, in the local population.

                4. A Phase 2A, multicenter trial (PITRI Trial) involving 6 public hospitals began in 2017, to assess whether Cangrelor administered prior to reperfusion would reduce acute MI size and MVO as assessed by Cardiac MRI.

                5. A multicenter study (FFRB Study) designed to determine the diagnostic performance of noninvasive fractional flow reserve (FFRB and FFRAM) with CCTA data in patients with intermediate coronary artery disease (CAD), as compared to an invasive FFR reference standard.

                6. A multicenter study (MYOVAx study) involved 8 public hospitals designed to study understand the pathophysiology of myocarditis associated with COVID19 vaccines.

                7. The ATTRaCT programme aims to build on Singapore’s competitive advantages in advanced cardiac imaging, genetic and molecular studies to develop "one-stop" platform spanning from human to large and small animal models, dedicated to deepening our understanding of CV disease progression, discovery of new targets and repurposing of drugs. The ATTRaCT platform integrates, for the first time, top expertise in CV clinical and biomedical sciences across the entire nation, by partnering each BMRC RI (SBIC, GIS, SIgN, IMCB) with each of the 2 only national heart institutions (NHCS, NUHCS) as well as academic institutions (NUS, Duke-NUS). ATTRaCT exploits current capacity around the unique Singapore-led ASIAN-HF network involving 6 site within Singapore (NUHCS, NHCS, TTSH, CGH, KTPH, SGH)

                8. ADOPT is a prospective multinational randomized open-label, parallel group, active-controlled, two-arm, long-term morbidity and mortality trial involving 6 Asian regions (Singapore, Malaysia, China, Taiwan, India, United Arab Emirates; estimated 4-6 sites each) to test if intensive preventive treatment strategy (high renin angiotensin system [RAASi], beta-blockade, SGLT2i) may be associated with reduced cardiovascular (CV) events compared to standard of care.


                        We assisted one of our investigator initiated study SingHEART project to collaborate with Nestec (research arm of Nestlé) to start a new sub-study called ARROW, which recruited 100 healthy individuals from the SingHEART cohort for a food challenge study. This is a novel collaboration where investigations on phenotypic and genotypic correlations come together with nutritional factors and serves as an example of how we attract external funding from industry partner for our clinical research studies.

                        We also provided recruitment support to our institution MOH registered tissue bank- NHCS Biobank since 2013. As of 31 Dec 2021, we assist in recruiting 5138 participants to donate biological samples to NHCS Biobank for future research.


                        Achievements

                        Awards

                        1. HEALTH AND BIOMEDICAL SCIENCES (HBMS) INDUSTRY ALIGNMENT FUND PRE-POSITIONING (IAF-PP) - $7185,600 (inclusive overhead)

                        2. MOH COVID-19 Research Fund - S$398,963.50 (inclusive overhead)

                        3. A*STAR BMRC STRATEGIC POSITIONING FUND (SPF) - $2,846,250.00

                        4. NMRC CLINICAL TRIAL GRANT – INDUSTRY COLLABORATIVE TRIALS SCHEME (CTG-ICT) - $1,500,000, inclu. 20% Indirect Research Cost (IRC)


                                    Publications

                                    1. S D Anker, J Bulter, G Filippatos, J P Ferreira, E Bocchi, M Bohm, HPB La Rocca, D J Choi, V Chopra, E C Valenzuela, N Giannetti, J E Gomez-Mesa, S Janssens, J L Januzzi, J R Gonzalez-Juanatey, B Merkely, S J Nicholls, S V Perrone, I L Pina, P Ponikowski, M Senna, D Sim, J Spinar, I Squire, S Taddei, H Tsutsui, S Verma, D Vinereanu, J Zhang, P Carson, CSP Lam et al. Empagliflozin in Heart Failure with a Preserved Ejection Fraction. N Engl J Med 2021; 385:1451-1461.doi: 10.1056/NEJMoa2107038

                                    2. Ding C, Egli L, Bosco N, Sun L, Goh HJ, Yeo KK, Yap JJL, Actis-Goretta L, Leow MK, Magkos F. Plasma Branched-Chain Amino Acids Are Associated With Greater Fasting and Postprandial Insulin Secretion in Non-diabetic Chinese Adults. Front Nutr. 2021 Apr 28;8:664939. doi: 10.3389/fnut.2021.664939. PMID: 33996878; PMCID: PMC8113402

                                    3. Armand Valsesia, Leonie Egli, Nabil Bosco, Faidon Magkos, Siew Ching Kong, Lijuan Sun, Hui Jen Goh, Huang Weiting, Fabrizio Arigoni, Melvin Khee-Shing Leow, Khung Keong Yeo, Lucas Actis-Goretta, Clinical- and omics-based models of subclinical atherosclerosis in healthy Chinese adults: a cross-sectional exploratory study, The American Journal of Clinical Nutrition, Volume 114, Issue 5, November 2021, Pages 1752–1762, https://doi.org/10.1093/ajcn/nqab269

                                    4. 1Ponikowski P, Kirwan BA, Anker SD, McDonagh T, Dorobantu M, Drozdz J, Fabien V, Filippatos G, Göhring UM, Keren A, Khintibidze I, Kragten H, Martinez FA, Metra M, Milicic D, Nicolau JC, Ohlsson M, Parkhomenko A, Pascual-Figal DA, Ruschitzka F, Sim D, et al.; AFFIRM-AHF investigators. Ferric carboxymaltose for iron deficiency at discharge after acute heart failure: a multicentre, double-blind, randomised, controlled trial. Lancet. 2020 Dec 12;396(10266):1895-1904. doi: 10.1016/S0140-6736(20)32339-4. Epub 2020 Nov 13. PMID: 33197395.

                                    5. •2Ponikowski P, Kirwan BA, Anker SD, Dorobantu M, Drozdz J, Fabien V, Filippatos G, Haboubi T, Keren A, Khintibidze I, Kragten H, Martinez FA, McDonagh T, Metra M, Milicic D, Nicolau JC, Ohlsson M, Parhomenko A, Pascual-Figal DA, Ruschitzka F, Sim D, et al. Rationale and design of the AFFIRM-AHF trial: a randomised, double-blind, placebo-controlled trial comparing the effect of intravenous ferric carboxymaltose on hospitalisations and mortality in iron-deficient patients admitted for acute heart failure. Eur J Heart Fail. 2019 Dec;21(12):1651-1658. doi: 10.1002/ejhf.1710.

                                    6. Bulluck H, Chan MHH, Bryant JA, Chai P, Chawla A, Chua TS, Chung YC, Fei G, Ho HH, Ho AFW, Hoe AJ, Imran SS, Lee CH, Lim SH, Liew BW, Yun PLZ, Hock MOE, Paradies V, Roe MT, Teo L, Wong AS, Wong E, Wong PE, Watson T, Chan MY, Tan JW, Hausenloy DJ. Platelet inhibition to target reperfusion injury trial: Rationale and study design. Clin Cardiol. 2019 Jan;42(1):5-12. doi: 10.1002/clc.23110. Epub 2018 Dec 17. PMID: 30421441; PMCID: PMC6436500.

                                    7. Tan XW, Zheng Q, Shi L, Gao F, Allen JC, Coenen A, Baumann S, Schoepf UJ, Kassab GS, Lim ST, Wong AS, Tan JW, Yeo KK, Chin CT, Ho KW, Tan SY, Chua TS, Chan ES, Tan RS, Zhong L. Combined diagnostic performance of coronary computed tomography angiography and computed tomography derived fractional flow reserve for the evaluation of myocardial ischemia: A meta-analysis (2017). International Journal of Cardiology, 236:100-106.

                                    8. Zhang JM, Chandola G, Tan RS, Chai P, Teo LLS, Low R, Allen J, Huang W, Fam JM, Chin CY, Wong ASL, Low AF, Kassab GS, Chua T, Tan SY, Lim ST & Zhong L. Quantification of effects of mean blood pressure and left ventricular mass on noninvasive fast fractional flow reserve (2020). AJP-Heart and Circulatory Physiology, 319: H360–H369.

                                    9. Lena Bosch, Erberto Carluccio, Stefano Coiro, Lingli Gong, David Sim, Daniel Yeo, Fazlur Jaufeerally, Kui Toh Gerard Leong, Hean Yee Ong, Ng Tze Pin, Arthur Mark Richards, Fatih Arslan, Lieng Hsi Ling, Carolyn Lam*(*Corresponding author), Giuseppe Ambrosio. Risk stratification of Asian patients with Heart Failure and Reduced Ejection Fraction:The effectiveness of the "Echo Heart Failure Score". Eur J Heart Failure 2017 May; Vol 19; 12:1732-1735.

                                    10. Ingrid E.M. Bank, Crystel M. Gijsberts, Tiew-Hwa K. Teng, Lina Benson, David Sim, Poh Shuan Daniel Yeo, Hean Yee Ong, Fazlur Jaufeerally, Gerard K.T. Leong, Lieng H. Ling, Mark A. Richards, Dominique P.V. de Kleijn, Ulf Dahlström, Lars H. Lund, Carolyn S.P. Lam. Prevalence and Clinical Significance of Diabetes in Asian Versus White Patients With Heart Failure. JACC Heart Fail. 2017 Jan;5(1):14-24. doi: 10.1016/j.jchf.2016.09.015.

                                    11. Lena Bosch*, Carolyn S.P. Lam* (*Joint first authors: both authors contributed equally to this manuscript), Lingli Gong, David Sim, Siew Pang Chan, Daniel Yeo, Fazlur Jaufeerally, Kui Toh Gerard Leong, Hean Yee Ong, Ng Tze Pin, Arthur Mark Richards, Fatih Arslan, Lieng H. Ling. Right ventricular dysfunction in left-sided heart failure with preserved versus reduced ejection fraction. Eur J Heart Failure 2017 Apr; Vol 19; 12-1664-1671.

                                    12. Chester Drum, Warren Tan, Siew-Pang Chan, Leroy Pakkiri, Jenny P.C. Chong, Oi Wah Liew, Tze Pin Ng, Lieng Ling, David Sim, Kui Tong Leong, Poh Shuan Daniel Yeo, Hean Yee Ong, Fazlur Jaufeerally, Raymond Wong, Ping Chai, Adrian Low, Pia Davidsson, Mathias Liljeblad, Ann-Sofi Soderling, Li-Ming Gan, Rattan Bhat, Kristy Purnamawati, Carolyn SP Lam, Arthur Richards. Thymosin beta-4 is elevated in women with heart failure with preserved ejection fraction. J Am Heart Assoc. 2017 Jun 13;6(6). pii: e005586. doi: 10.1161/JAHA.117.005586.

                                    13. Carolyn S.P. Lam, Greg D Gamble, Lieng H. Ling, David Sim, Kui Toh Gerard Leong, Poh Shuan Daniel Yeo, Hean Yee Ong, Fazlur Jaufeerally, Tze P Ng, Vicky A Cameron, Katrina Poppe, Mayanna Lund, Gerry Devlin, Richard Troughton, A. Mark Richards*, Robert N Doughty *(*Co-senior authors). Mortality Associated With Heart Failure With Preserved Versus Reduced Ejection Fraction In A Prospective International Multi-Ethnic Cohort Study. Eur Heart J. 2018 Jan 29. DOI:10.1093/eurheartj/ehy005.

                                    14. Jasper Tromp, A. Mark Richards, Wan Ting Tay, Tiew-Hwa K. Teng, Poh Suan , Daniel Yeo, David Sim, Fazlur Jaufeerally, Gerard Leong, Hean Yee Ong, Lieng Hsi Ling, Dirk J van Veldhuisen, Tiny Jaarsma, Adriaan A. Voors, Peter van der Meer, Rudolf de Boer, Carolyn S P Lam. NT-proBNP and Prognosis in Caucasian versus Asian Patients with Heart Failure. ESC Heart Failure 2018 Apr; 5(2):279-287. DOI: 10.1002/ehf2.12252. PMID: 29380931. Epub 2018 Jan 30.

                                    15. Eugene S J Tan, Wan Ting Tay, Tiew-Hwa Katherine Teng, David Sim, Kui Toh Gerard Leong, Poh Shuan Daniel Yeo, Hean Yee Ong, Fazlur Jaufeerally, Tze Pin Ng, Katrina Poppe, Mayanna Lund, Gerard Devlin, Richard W Troughton, Lieng Hsi Ling, Arthur Mark Richards, Robert N Doughty, Carolyn S P Lam. Ethnic differences in atrial fibrillation in patients with heart failure from Asia-Pacific. Heart. 2019 Jun 19. 105(11):842-847. doi: 10.1136/heartjnl-2018-314077. Epub 2019 Jan 19.

                                    16. Lee Lee Wong, Ruiyang Zou, Lihan Zhou, Jia Yuen Lim, Dominic Phua Cheng Yang, Chengcheng Liu, Jenny P.C. Chong, Jessica Y.X. Ng, Oi Wah Liew, Siew Pang Chan,Yei-Tsung Chen, Michelle M.Y. Chan, Poh Shuan D. Yeo, Tze Pin Ng, Lieng H. Ling, David Sim, Kui Toh G. Leong, Hean Y. Ong, Fazlur Jaufeerally, Raymond Wong, Ping Chai, Adrian F. Low, Mayanna Lund, Gerry Devlin, Richard Troughton, Vicky A. Cameron, Robert N Doughty, Carolyn S.P. Lam, Heng-phon Too and Arthur Mark Richards. Combining Circulating MicroRNA and NT-proBNP to Detect and Categorize Heart Failure Subtype. Journal of the American College of Cardiology. Vol.73, Issue 11, Mar 2019. https://doi.org/10.1016/j.jacc.2018.11.060.

                                    17. Tromp J, Bryant JA, Jin X, van Woerden G, Asali S, Yiying H, Liew OW, Ching JCP, Jaufeerally F, Loh SY, Sim D, Lee S, Soon D, Tay WT, Packer M, van Veldhuisen DJ, Chin C, Richards AM, Lam CSP. Epicardial fat in heart failure with reduced versus preserved ejection fraction. European Journal of Heart Failure 2021 Mar 16 doi: 10.1002/ejhf.2156.