LOnger-term Effects of COVID-19 INfection on Blood Vessels And Blood pRessure (LOCHINVAR)

Hypertension Clinical Trial

— LOCHINVAR  

Official title:

Longer-term Effects of COVID-19 on Blood Vessels and Blood Pressure (LOCHINVAR) Phenotyping Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05087290
• Other study ID #: GN20CA501
• Secondary ID: 21/WS/0075299056
• Status: Completed
• Start date: September 30, 2021
• Est. completion date: September 21, 2023

Study information

• Verified date: September 2023
• Source: University of Glasgow
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The COVID-19 pandemic is the biggest medical challenge in decades. Individuals with pre-existing cardiovascular diseases have a higher risk of severe disease and death from COVID-19. The SARS-CoV-2 virus causes infection by targeting a molecule on the walls of the cells lining the lungs and the blood vessels leading to injury. There are concerns that after recovery from COVID-19, the damage sustained by these cells may have long-term consequences including high blood pressure, stroke and heart attacks. The burden of high blood pressure as a result of the pandemic is unknown and a greater understanding of COVID-19 impact on blood pressure and its underlying mechanisms is urgently needed.

LOCHINVAR is based on our pilot study "COVID-19 blood pressure endothelium interaction study" (OBELIX,NCT04409847, IRAS 284453), which found that patients with normal blood pressure at the time of hospital admission with COVID-19 showed a nine-point higher blood pressure ≥12 weeks after recovery, compared to a group without COVID-19. LOCHINVAR will extend the OBELIX study aiming to establish if COVID-19 increases the risk of developing high blood pressure and investigating underlying mechanisms through detailed measurements of blood pressure, blood vessel function, hormones and chemicals in the blood, urine and stool.

The investigators will invite 150 adults without pre-existing high blood pressure who were discharged from hospital after an admission: half with COVID-19 and half without. Baseline visit will be ≥12 weeks after discharge for measurements of blood pressure, tests of heart and blood vessel health, blood, urine and stool samples along with questionnaires on mood and quality of life. Two further study visits follow, at 12 and 18 months.

This study will generate crucial evidence on the long-term impact of COVID-19 on blood pressure along with information on potential mechanisms of this effect with immediate, transferable impact on clinical practice and inform risk mitigation measures.

Description:

The Coronavirus Disease-19 (COVID-19) pandemic is one of the biggest medical challenges in recent years. Whilst COVID-19 primarily affects the lungs, causing interstitial pneumonitis and severe acute respiratory distress syndrome, it also affects multiple organ systems, including the cardiovascular system(1-3). There are documented associations between severity of disease/mortality risk and advancing age, male sex and associated comorbid disease (hypertension, ischaemic heart disease, diabetes, obesity, COPD and cancer).(4,5) The most common complications include cardiac dysrhythmia(6,7), cardiac injury(8,9), myocarditis, heart failure, pulmonary embolism10 and disseminated intravascular coagulation(11).

The SARS-CoV-2 virus uses the ACE2 receptor (ACE2) to enter type 2 pneumocytes, macrophages, perivascular pericytes, and cardiomyocytes.(12) This may lead to myocardial dysfunction and damage, endothelial dysfunction, microvascular dysfunction, plaque instability, and myocardial infarction.(12) In addition, ACE2 is expressed in several other organs including cells lining the blood vessels (endothelial cells), ACE2 is a key player in the renin-angiotensin system (RAS) which is important in blood pressure regulation and is a target for some of the commonly used drugs used in the treatment of blood pressure. While ACE2 is essential for viral invasion, it is unclear if the use of the common antihypertensive drugs ACE inhibitors or angiotensin receptor blockers (ARBs) alter prognosis in those with COVID-19 infection.(12) Furthermore, there is evidence that the normally occurring bacteria in the gut (gut microbiome) directly influences the makeup of the human immune system and has been implicated in severity of COVID-19 as well as in the magnitude of the immune system response to SARS-CoV-2 infection(13).

This study (LOCHINVAR) is based on the pilot study "COVID-19 blood pressure endothelium interaction study" (OBELIX), funded by the Chief Scientific Office. Preliminary results showed that participants who had COVID-19 infection had an 8.6mmHg increase in their average 24hr systolic blood pressure, compared to those that did not have COVID-19 infection. The investigators will increase our recruitment of potential participants to meet our sample size of 150 participants (75 SARS-CoV-2 +ve cases and 75 SARS-CoV-2 -ve cases) built on OBELIX. This study will allow us to have a better understanding of the risks of developing high blood pressure or uncontrolled blood pressure following COVID-19 infection. This will allow doctors to be able to make a recommendation on the current/long term management of people with high blood pressure beyond the pandemic.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 150
• Est. completion date: September 21, 2023
• Est. primary completion date: September 21, 2023
• Gender: All
• Age group: 30 Years to 60 Years

Eligibility

Inclusion Criteria:

• Age 30-60 years

• Admission between 01/09/2020 - 31/12/2021

• Clinically suspected or Confirmed COVID-19 Reverse Transcription-Polymerase Chain Reaction (RT-PCR) test confirmed COVID-19 on admission

• No history of hypertension or current drug treatment for hypertension

Controls

1. Age 30-60

2. No history of hypertension

3. No antihypertensive drugs

4. Confirmed RT-PCR test negative and admission through Queen Elizabeth University Hospital immediate assessment unit and acute receiving units 01/09/2020 to 31/12/2021 or no history of SARS-CoV-2 infection or COVID-19

Exclusion Criteria:

Inability to give informed consent/lack of capacity BMI >40 eGFR <60 ml/min Pregnancy History of

• Cancer within 5 years

• Persistent atrial fibrillation

• Severe illness, at investigator discretion Prescription of

• BP lowering drugs

• Oral Corticosteroid (chronic use)

• Immunosuppressive agents

• Oral NSAIDs (chronic use)

Related Conditions & MeSH terms

• COVID-19
• Covid19
• Hypertension

Intervention

Other:
• Cases
All performed at baseline, 12 months and 18 months Medical and drug history Anthropometric tests Electrocardiogram Brachial flow mediated dilatation 6 minute walk test Blood sampling Urine sampling 24-hr Ambulatory Blood Pressure Monitor Questionnaires Optional: Stool sampling,24-hr Urine collection, Home Blood Pressure Monitor
• Controls
All performed at baseline, 12 months and 18 months Medical and drug history Anthropometric tests Electrocardiogram Brachial flow mediated dilatation 6 minute walk test Blood sampling Urine sampling 24-hr Ambulatory Blood Pressure Monitor Questionnaires Optional: Stool sampling,24-hr Urine collection, Home Blood Pressure Monitor

Locations

Country	Name	City	State
United Kingdom	Professor Sandosh Padmanabhan	Glasgow

Sponsors (1)

Lead Sponsor	Collaborator
University of Glasgow

Country where clinical trial is conducted

United Kingdom, 

References & Publications (13)

Danzi GB, Loffi M, Galeazzi G, Gherbesi E. Acute pulmonary embolism and COVID-19 pneumonia: a random association? Eur Heart J. 2020 May 14;41(19):1858. doi: 10.1093/eurheartj/ehaa254. No abstract available. — View Citation

Driggin E, Madhavan MV, Bikdeli B, Chuich T, Laracy J, Biondi-Zoccai G, Brown TS, Der Nigoghossian C, Zidar DA, Haythe J, Brodie D, Beckman JA, Kirtane AJ, Stone GW, Krumholz HM, Parikh SA. Cardiovascular Considerations for Patients, Health Care Workers, and Health Systems During the COVID-19 Pandemic. J Am Coll Cardiol. 2020 May 12;75(18):2352-2371. doi: 10.1016/j.jacc.2020.03.031. Epub 2020 Mar 19. — View Citation

Guzik TJ, Mohiddin SA, Dimarco A, Patel V, Savvatis K, Marelli-Berg FM, Madhur MS, Tomaszewski M, Maffia P, D'Acquisto F, Nicklin SA, Marian AJ, Nosalski R, Murray EC, Guzik B, Berry C, Touyz RM, Kreutz R, Wang DW, Bhella D, Sagliocco O, Crea F, Thomson EC, McInnes IB. COVID-19 and the cardiovascular system: implications for risk assessment, diagnosis, and treatment options. Cardiovasc Res. 2020 Aug 1;116(10):1666-1687. doi: 10.1093/cvr/cvaa106. — View Citation

Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15;395(10223):497-506. doi: 10.1016/S0140-6736(20)30183-5. Epub 2020 Jan 24. Erratum In: Lancet. 2020 Jan 30;: — View Citation

Lippi G, Lavie CJ, Sanchis-Gomar F. Cardiac troponin I in patients with coronavirus disease 2019 (COVID-19): Evidence from a meta-analysis. Prog Cardiovasc Dis. 2020 May-Jun;63(3):390-391. doi: 10.1016/j.pcad.2020.03.001. Epub 2020 Mar 10. No abstract available. — View Citation

Liu K, Fang YY, Deng Y, Liu W, Wang MF, Ma JP, Xiao W, Wang YN, Zhong MH, Li CH, Li GC, Liu HG. Clinical characteristics of novel coronavirus cases in tertiary hospitals in Hubei Province. Chin Med J (Engl). 2020 May 5;133(9):1025-1031. doi: 10.1097/CM9.0000000000000744. — View Citation

Richardson S, Hirsch JS, Narasimhan M, Crawford JM, McGinn T, Davidson KW; the Northwell COVID-19 Research Consortium; Barnaby DP, Becker LB, Chelico JD, Cohen SL, Cookingham J, Coppa K, Diefenbach MA, Dominello AJ, Duer-Hefele J, Falzon L, Gitlin J, Hajizadeh N, Harvin TG, Hirschwerk DA, Kim EJ, Kozel ZM, Marrast LM, Mogavero JN, Osorio GA, Qiu M, Zanos TP. Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area. JAMA. 2020 May 26;323(20):2052-2059. doi: 10.1001/jama.2020.6775. Erratum In: JAMA. 2020 May 26;323(20):2098. — View Citation

Ruan Q, Yang K, Wang W, Jiang L, Song J. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 2020 May;46(5):846-848. doi: 10.1007/s00134-020-05991-x. Epub 2020 Mar 3. No abstract available. Erratum In: Intensive Care Med. 2020 Apr 6;: — View Citation

Segal JP, Mak JWY, Mullish BH, Alexander JL, Ng SC, Marchesi JR. The gut microbiome: an under-recognised contributor to the COVID-19 pandemic? Therap Adv Gastroenterol. 2020 Nov 24;13:1756284820974914. doi: 10.1177/1756284820974914. eCollection 2020. — View Citation

Shi S, Qin M, Shen B, Cai Y, Liu T, Yang F, Gong W, Liu X, Liang J, Zhao Q, Huang H, Yang B, Huang C. Association of Cardiac Injury With Mortality in Hospitalized Patients With COVID-19 in Wuhan, China. JAMA Cardiol. 2020 Jul 1;5(7):802-810. doi: 10.1001/jamacardio.2020.0950. — View Citation

Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020 Apr;18(4):844-847. doi: 10.1111/jth.14768. Epub 2020 Mar 13. — View Citation

Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, Wang B, Xiang H, Cheng Z, Xiong Y, Zhao Y, Li Y, Wang X, Peng Z. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA. 2020 Mar 17;323(11):1061-1069. doi: 10.1001/jama.2020.1585. Erratum In: JAMA. 2021 Mar 16;325(11):1113. — View Citation

Zheng YY, Ma YT, Zhang JY, Xie X. COVID-19 and the cardiovascular system. Nat Rev Cardiol. 2020 May;17(5):259-260. doi: 10.1038/s41569-020-0360-5. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	% Flow Mediated Dilatation	% Brachial Flow Mediated Dilatation at 12 months and 18 months in SARS-CoV-2 +ve cases and in SARS-CoV-2 -ve controls	12 months and 18 months
Other	Exercise tolerance - distance walked in 6 minutes	Exercise tolerance distance walked in 6 minutes at 12 months and 18 months in SARS-CoV-2 +ve cases and in SARS-CoV-2 -ve controls	12 months and 18 months
Other	Quality of life and mood - difference in longitudinal changes in QoL and mood between groups	Patient Health Questionaire-9 (Minimal Depression 0-4, Mild Depression 5 - 9, Moderate Depression 10-14, Moderately Severe Depression 15 - 19, Severe Depression 20-27) and Euroqol (EQ5D-3L) Questionnaire (Mean EQ-5D and Standard Deviation) at 12 months and 18 months in SARS-CoV-2 +ve cases and in SARS-CoV-2 -ve controls	12 months and 18 months
Other	Mean Home Systolic Blood Pressure	Mean Home Blood Pressure Measurements - Systolic Blood Pressure at 12 months and 18 months in SARS-CoV-2 +ve cases and in SARS-CoV-2 -ve controls	12 months and 18 months
Other	Mean Home Diastolic Blood Pressure	Mean Home Blood Pressure Measurements - Diastolic Blood Pressure at 12 months and 18 months in SARS-CoV-2 +ve cases and in SARS-CoV-2 -ve controls	12 months and 18 months
Other	Day Home Systolic Blood Pressure	Average Day Home Blood Pressure Measurements - Systolic Blood Pressure at 12 months and 18 months in SARS-CoV-2 +ve cases and in SARS-CoV-2 -ve controls	12 months and 18 months
Other	Evening Home Systolic Blood Pressure	Average Evening Home Blood Pressure Measurements - Systolic Blood Pressure at 12 months and 18 months in SARS-CoV-2 +ve cases and in SARS-CoV-2 -ve controls	12 months and 18 months
Other	Day Home Diastolic Blood Pressure	Average Day Home Blood Pressure Measurements - Diastolic Blood Pressure at 12 months and 18 months in SARS-CoV-2 +ve cases and in SARS-CoV-2 -ve controls	12 months and 18 months
Other	Evening Home Diastolic Blood Pressure	Average Evening Home Blood Pressure Measurements - Diastolic Blood Pressure at 12 months and 18 months in SARS-CoV-2 +ve cases and in SARS-CoV-2 -ve controls	12 months and 18 months
Primary	24-hour ABPM Systolic Blood Pressure	Average 24 hour Ambulatory Blood Pressure Monitoring - Systolic Blood Pressure , (all day and night) at 12 months in SARS-CoV-2 +ve cases and in SARS-CoV-2 -ve controls	12 months
Secondary	24-hour ABPM Diastolic Blood Pressure	Average 24 hour Ambulatory Blood Pressure Monitoring - Diastolic Blood Pressure, 24hr (all day and night) at 12 months and 18 months in SARS-CoV-2 +ve cases and in SARS-CoV-2 -ve controls	12 months and 18 months
Secondary	Day ABPM Systolic Blood Pressure	Day Ambulatory Blood Pressure Monitoring (Average Systolic Blood Pressure) 8 am to 8 pm at 12 months and 18 months in SARS-CoV-2 +ve cases and in SARS-CoV-2 -ve controls	12 months and 18 months
Secondary	Day ABPM Diastolic Blood Pressure	Day Ambulatory Blood Pressure Monitoring (Average Diastolic Blood Pressure), 8 am to 8 pm at 12 months and 18 months in SARS-CoV-2 +ve cases and in SARS-CoV-2 -ve controls	12 months and 18 months
Secondary	Night ABPM Systolic Blood Pressure	Night Ambulatory Blood Pressure Monitoring (Average Systolic Blood Pressure) 8pm to 8 am at 12 months and 18 months in SARS-CoV-2 +ve cases and in SARS-CoV-2 -ve controls	12 months and 18 months
Secondary	Night ABPM Diastolic Blood Pressure	Night Ambulatory Blood Pressure Monitoring (Average Diastolic Blood Pressure) 8pm to 8 am at 12 months and 18 months in SARS-CoV-2 +ve cases and in SARS-CoV-2 -ve controls	12 months and 18 months
Secondary	24-hour ABPM Heart Rate	24 hour Ambulatory Blood Pressure Monitoring - Heart Rate, 24hr (all day and night) at 12 months and 18 months in SARS-CoV-2 +ve cases and in SARS-CoV-2 -ve controls	12 months and 18 months
Secondary	24-hour Urine Sodium	24-hour Urine Sodium at 12 months and 18 months in SARS-CoV-2 +ve cases and in SARS-CoV-2 -ve controls	12 months and 18 months

External Links

•   OBELIX Study