Study of the Treatment and Outcomes in Critically Ill Patients With COVID-19 and High Risk of Acute Kidney Injury

The aim is to describe the epidemiology and determine the independent risk factors for mortality and acute organ injury in AKI and to assess the impact of different treatment strategies on survival. This will allow the development of prevention strategies and design of appropriately powered intervention studies.

Study Overview

• Status: Recruiting
• Conditions: Critical Illness; Acute Kidney Injury; COVID

Detailed Description

Since the outbreak of coronavirus disease 2019 (COVID-19) began in December 2019 in China, over 1 million people have been infected and over 55,000 have died worldwide, and these numbers continue to rise. Combating this pandemic requires a multidisciplinary approach from the medical research community, including translational studies to understand the pathogenesis of disease, randomized controlled trials of novel and re-purposed pharmacotherapies, and rigorously conducted epidemiologic studies that include granular patient-level data.

Current knowledge of the clinical features and outcomes of COVID-19 is mostly limited to studies from China and Italy. In one of the larger such studies, which consisted of 1099 patients hospitalized in mainland China, only 173 (16%) were classified as having severe disease, and only 15 (1.4%) died. The study was therefore inadequately powered to determine independent risk factors for death. A larger study consisting of 72,314 patients was recently published by the Chinese Center for Disease Control and Prevention. This nationwide registry study identified several important findings, including the striking monotonic relationship between older age and greater risk of death. Important limitations of the study, however, were lack of granular patient-level data and relatively few patients (<5% of the cohort) who were critically ill. Among critically ill patients with COVID-19, acute mortality rates have been reported to be as high as 49-62%, underscoring the importance of studying this patient population. Data from the United Kingdom (UK) suggest that >50% of critically ill patients have a degree of acute kidney injury (AKI) and >20% need renal replacement therapy (RRT). Mortality is particularly high in those who are mechanically ventilated and need RRT (>75%).

Detailed information about the risk of AKI, contributing factors and reasons for high mortality in critically ill COVID-19 patients is lacking. To meet this urgent need, the investigators plan to collect clinical data from >250 critically ill patients with COVID-19 admitted to the intensive care unit (ICU) at Guy's & St Thomas' Hospital. The investigators will collaborate with Dr Gupta and Prof Leaf from Harvard Medical School, Boston (US) who are leading a similar study across >50 sites in the United States.

The aim is to describe the epidemiology and determine the independent risk factors for mortality and acute organ injury in AKI and to assess the impact of different treatment strategies on survival. This will allow the development of prevention strategies and design of appropriately powered intervention studies.

• Study Type: Observational
• Enrollment (Anticipated): 300

Contacts and Locations

• Study Contact: Name: Marlies Ostermann, MD, PhD; Phone Number: 83036 0044 207 188 3038; Email: Marlies.Ostermann@gstt.nhs.uk
• Study Contact Backup: Name: Nuttha Lumlertgul, MD, PhD; Phone Number: 83036 0044 207 188 3038; Email: Nuttha.Lumlertgul@gstt.nhs.uk

Study Locations

• United Kingdom
  • London, United Kingdom, SE1 7EH
    • Recruiting
    • Guy's & St Thomas' Hospital
    • Contact: Marlies Ostermann, MD, PhD; Phone Number: 020 71883038; Email: Marlies.Ostermann@gstt.nhs.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Adult critically ill patients with confirmed diagnosis of COVID-19

Description

Inclusion Criteria:

1. Adults (aged ≥18 years)
2. Confirmed diagnosis of COVID-19
3. Hospitalized in the ICU for illness related to COVID-19

4. Any of the following:

   • Current in-patient in ICU
   • Previous in-patient in ICU and died in ICU or hospital
   • Previous in-patient in ICU and discharged from ICU alive

Exclusion Criteria:

1. Younger than 18 years old
2. On chronic dialysis within the last year or on dialysis at ICU admission
3. Functioning kidney transplant
4. No creatinine within 48 hours of ICU admission

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Critically Ill Patients with COVID-19; We plan to recruit patients who are admitted to intensive care units with COVID-19 diagnosis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of any stage of acute kidney injury	As defined by Kidney Diseases: Improving Global Outcomes (KDIGO) criteria	14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality	Mortality	14-day, hospital, and intensive care unit (ICU) mortality
Renal recovery	Defined by return of creatinine to < 1.5 times of baseline	14 days
Percentage of patients who receive renal replacement therapy	Percentage	14 days
Percentage of participants who are dialysis dependent	Percentage of participants who are dialysis dependent	Through study completion, an average of 90 days
Free-days of vasoactive medications and mechanical ventilation	Days without vasoactive medications and mechanical ventilation	Day 30
Length of intensive care unit and hospital stay	Length of intensive care unit and hospital stay	Through study completion, an average of 90 days
Number of participants with consequences following AKI	Congestive heart failure, Arrhythmia, Acute respiratory distress syndrome, Septic shock, Acute cardiac injury, pneumonia	Through study completion, an average of 90 days
Time from illness onset to need for mechanical ventilator support	Time from illness onset to need for mechanical ventilator support	Through study completion, an average of 30 days

Collaborators and Investigators

• Sponsor: Guy's and St Thomas' NHS Foundation Trust
• Collaborators: Harvard Medical School (HMS and HSDM)
• Investigators: Principal Investigator: Nuttha Lumlertgul, MD, PhD, Guy's & St Thomas' Hospital

Publications and helpful links

General Publications

• Lumlertgul N, Pirondini L, Cooney E, Kok W, Gregson J, Camporota L, Lane K, Leach R, Ostermann M. Acute kidney injury prevalence, progression and long-term outcomes in critically ill patients with COVID-19: a cohort study. Ann Intensive Care. 2021 Aug 6;11(1):123. doi: 10.1186/s13613-021-00914-5.

Study record dates

Study Major Dates

• Study Start (Actual): June 20, 2020
• Primary Completion (Anticipated): July 31, 2022
• Study Completion (Anticipated): December 31, 2022

Study Registration Dates

• First Submitted: May 27, 2020
• First Submitted That Met QC Criteria: June 23, 2020
• First Posted (Actual): June 24, 2020

Study Record Updates

• Last Update Posted (Actual): August 4, 2021
• Last Update Submitted That Met QC Criteria: August 3, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Kidney Diseases; Urologic Diseases; Disease Attributes; Renal Insufficiency; Wounds and Injuries; Critical Illness; Acute Kidney Injury
• Other Study ID Numbers: 283672

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No