• CCM Epidemiology
• Emerging Infections & Pandemic Preparedness
• Patient & Public Involvement & Engagement
• Antimicrobial Resistance and Stewardship
• Long-term outcomes of Critical Illness
• Genomics in Critical Care
• Trials Methodology
• Machine Learning

Oxygen requirements and approaches to respiratory support in patients with COVID-19 in low- and middle-income countries (O2CoV2) was an observational study conducted by WHO between March – April 2022. The study aimed to characterise type and duration of different modalities of oxygen therapy delivered to patients; describe demographics and outcomes of hospitalised patients with COVID-19; and describe facility-level oxygen production and support. The study was implemented in 30 countries representing four LMICs from each of the six WHO regions. Pakistan successfully contributed 67 enrolments.

REMAP, is a Randomised, Embedded, Multifactorial, Adaptive Platform trial. The broad objective of this trial is, over time, to determine and continuously update the optimal set of treatments for community-acquired pneumonia. This trial is an innovative global research initiative designed to improve the treatment of community-acquired pneumonia (CAP) including COVID-19, particularly in severe cases that require admission to an Intensive Care Unit (ICU). REMAP-CAP uses an adaptive platform trial design that allows for the simultaneous testing of multiple treatments across different domains. The trial evolves by incorporating new treatment options and adjusting strategies based on real-time data.

Ziauddin University is the coordinating center for other REMAP-CAP sites and successfully enrolled patients in the Vitamin C, Ivermectin, Statin, and Oseltamivir domains. In the Ivermectin domain, 98% of enrollments are from Pakistan.
https://www.remapcap.org/participating-sites

The Mega-ROX trial is a large-scale, multi-center, randomized clinical study investigating optimal oxygen therapy strategies for mechanically ventilated adults in intensive care. Embedded within PRICE, this study examines whether a conservative approach to oxygen therapy reduces mortality compared to a liberal approach, while also exploring whether liberal oxygen therapy may benefit certain groups, such as patients with acute brain pathologies (excluding hypoxic brain injuries) and those with sepsis. Ziauddin University contributes to this global effort with an enrollment number of 236 patients, as of July 2024, with Pakistan accounting for 20% of the total enrollments.

https://www.anzics.org/

ACORN-HAI is a surveillance designed to address the growing threat of antimicrobial resistance (AMR) in healthcare-associated infections (HAIs) within Pakistan. This project focuses on severe infections, particularly in intensive care units (ICUs), surgical wards, and cancer care settings, where multidrug-resistant organisms (MDROs) are most prevalent. The study aims to monitor and document the incidence and prevalence of AMR in HAIs, specifically focusing on bloodstream infections (BSI) and ventilator-associated pneumonia (VAP).

Ziauddin University has successfully implemented the study across both North and Clifton campuses and has enrolled 212 patients as of October 2024.

https://wellcomeopenresearch.org/articles/8-179

GenOMICC investigates the genetic factors influencing susceptibility to life-threatening infections and sterile injuries. In collaboration with the International Severe Acute Respiratory Infection Consortium (ISARIC) and the International Forum of Acute Care Trialists (InFACT), this study aims to establish a DNA resource for genome-wide discovery of host genetic variants that affect patient outcomes. By analyzing DNA samples from critically ill patients in Pakistan, the research seeks to identify key genetic mechanisms that could lead to new therapeutic targets for improving survival in severe infections and systemic injuries.

Ziauddin University is the coordinating center for other GenOMICC sites achieving 299 successful enrollments as of September 2024.

https://genomicc.org/countries/pakistan/

• Clinical Characterisation Protocol for Severe and Emerging Infections (CCP)

The  ISARIC-WHO Clinical Characterisation Protocol (CCP) is a standardized protocol for the rapid, coordinated clinical investigation of severe or potentially severe illness caused by emerging or high-consequence pathogens or other noxious exposures of public health interest. It is an adaptable protocol depending on a site’s resources and works in a tiered approach:

• • Tier 0: Data collection
  • Tier 1: Data collection and on-admission samples
  • Tier 2 – 3: Data collection and serial sampling depending on resources

During the COVID-19 pandemic, CCP was successfully embedded into the Pakistan Registry of Intensive CarE (PRICE) platform, facilitating the enrollment of 9,102 COVID-19 patients across 69 ICUs in Pakistan.

• Characteristics and outcomes of patients with severe Dengue

A prospective observational study designed to analyze the clinical presentation, disease progression, and outcomes of patients with severe dengue in intensive care units (ICUs) across Pakistan. The project leverages ISARIC-WHO Clinical Characterisation Partnership (CCP) framework which is designed to capture globally harmonized data on dengue and is publicly accessible through;

https://isaric.org/research/dengue/dengue-clinical-characterisation-protocol/

• COVID-19 FOLLOW-UP

A multicenter, prospective and retrospective observational study to assess the long-term impacts of COVID-19 on ICU survivors across Pakistan. This study examines the prevalence of Long-COVID symptoms and monitors both physical and psychosocial outcomes in patients with confirmed or suspected SARS-CoV-2 infection. Using the ISARIC-WHO COVID-19 follow-up protocol, the study conducted retrospective follow-up on patients discharged between August 1, 2021, and January 31, 2022, and follows new ICU admissions at regular six-month intervals in a prospective cohort.

https://isaric.org/research/covid-19-clinical-research-resources/covid-19-long-term-follow-up-study/

The Pakistan Registry of Intensive CarE (PRICE) is a network of more than eighty intensive care units (ICUs) across Pakistan, including both public and private sector institutions. Established as a clinician-led initiative, PRICE aims to standardize and improve critical care practices throughout the country. The registry prospectively collects clinical and demographic data on consecutive adult ICU admissions, providing detailed information on the case mix, including presentation, diagnosis, comorbidities, severity of illness, organ support days, ICU mortality, and care processes. It provides a platform for evaluating the quality of care, implementing quality improvement initiatives, and facilitating registry-based research and platform trials within Pakistani ICUs.

https://reach.com.pk/price.html

A multicenter, randomized trial conducted between May 2020 and March 2022. It aimed to assess whether medical masks provided non-inferior protection compared to N95 respirators in preventing COVID-19 among healthcare workers. Participants were randomly assigned to wear either medical masks or fit-tested N95 respirators for 10 weeks. The study was conducted across 29 healthcare facilities in Canada, Israel, Pakistan, and Egypt, involving 1,009 healthcare workers. Of these, 186 participants were from Pakistan.

https://doi.org/10.7326/M22-1966

The South Asian Hub lead by Professor Hashmi has taken initiatives to improve patient care in Pakistan by standardising data collection processes, which has led to the identification of gaps in patient management and fostered an informed ‘community of healthcare professionals’ within the network. Expanding on ISARIC’s preparedness endeavours and leveraging established connections within the Pakistan Registry of Intensive Care (PRICE), the integration of the ISARIC WHO Case Report Form into the PRICE registry has significantly enhanced data gathering efforts across 80 ICUs. This pioneering approach, which embeds data collection mechanisms within existing registries, enabled the REMAP-CAP collaborative to carry out their trial for COVID. Regular reports on outcomes of COVID-19 patients admitted to ICUs empowered healthcare professionals with valuable insights to optimise patient care.

Additionally, the Karachi Hub established a comprehensive framework for follow-up studies, incorporating approaches involving patient communities, including implementing follow-up calls post-discharge with access to medical professionals, and designing concise, user-friendly questionnaires for telephone surveys.

https://isaric.org/regional-hubs-case-studies/ – pakistan

The Critical Care Research Team has been awarded the prestigious WHO-SHQ-RFP-24-2020 grant for their proposal to create a globally applicable Clinical Trials Unit (CTU) maturity framework. The project will focus on developing standards and guidance for CTUs, ensuring their capacity to manage high-quality clinical trials in diverse settings. The framework will be piloted across multiple WHO regions, enhancing its global applicability and impact.