Adult Respiratory Failure Intervention Study Africa (ARISE-AFRICA)

A Multicentre, Randomized, Clinical Trial of Respiratory Support With Standard Low Flow Oxygen Therapy, Continuous Positive Airway Pressure, and High-flow Oxygen Therapy in Adults With Acute Hypoxemic Respiratory Failure in Uganda

The dearth of Intensive care units in low resource settings portends for poor outcomes amongst patients with acute hypoxemic respiratory failure (AHRF) . To our knowledge, the effect of CPAP and HFNC on major outcomes has not been assessed in adults with AHRF in resource-limited settings. The aim of this prospective, multicenter, randomized, controlled, trial is to determine whether High-flow oxygen through a nasal cannula (HFNC) or Continuous positive airway pressure (CPAP) system can reduce mortality among patients with acute hypoxemic respiratory failure (AHRF) in a limited resource setting as compared with standard low flow oxygen therapy?

Study Overview

• Status: Completed
• Conditions: Acute Respiratory Distress Syndrome; Acute Lung Injury; Acute Respiratory Failure With Hypoxia
• Intervention / Treatment: Procedure: HFNC; Procedure: Standard Oxygen; Procedure: CPAP

Detailed Description

The care for the critically ill patient typically takes place in the intensive care unit (ICU). ICU care is quite expensive, even in resource rich countries. The most common reason for ICU admission globally is respiratory support for acute hypoxemic respiratory failure (AHRF). In patients with AHRF, the need for invasive mechanical ventilation is associated with high mortality, especially in low income countries (LICs), given the scarce availability of invasive mechanical ventilation. Some studies suggest that administration of ventilatory support through a mask may be effective in resource-limited settings. However, there is no clinical study data in adults to support this evidence. Human and material constraints are major barriers for the care of critically-ill patients in resource limited settings , advocating the need for a frugal approach. Furthermore, the scarcity of intensive care unit care in LICs contributes to a high mortality among acutely ill patients. The current corona virus pandemic has further highlighted the need for frugal acute care interventions in LICs.

Continuous positive airway pressure (CPAP) is a simple to use and affordable technique for noninvasive ventilatory support. High-flow oxygen through a nasal cannula (HFNC) may also offer an alternative in patients with hypoxemia. The high flow rates may also decrease physiological dead space by flushing expired carbon dioxide from the upper airway, a process that potentially explains the observed decrease in the work of breathing.

Frugal CPAP or HFNC , as compared with standard oxygen therapy, could reduce the mortality among adults presenting with AHRF in a resource-limited setting.

• Study Type: Interventional
• Enrollment (Actual): 705
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Uganda
  • Entebbe, Uganda
    • Entebbe Regional Referral Hospital
  • Gulu, Uganda
    • St Mary's, Lacor
  • Hoima, Uganda
    • Hoima Regional referral Hospital
  • Jinja, Uganda
    • Jinja Regional Referral Hospital
  • Kabale, Uganda
    • Kabale Regional Referral Hospital
  • Kampala, Uganda
    • Nsambya Hospital
  • Kampala, Uganda, 00256
    • Mulago National Specialised Hospital
  • Kampala, Uganda
    • Kampala hospital
  • Kampala, Uganda
    • Kiruddu National referral Hospital
  • Kampala, Uganda
    • Naguru Referral Hospital
  • Kampala, Uganda
    • Rubaga Hospital
  • Kampala, Uganda
    • TMR International Hospital
  • Kisoro, Uganda
    • Kisoro District Hospital
  • Masaka, Uganda
    • Masaka regional Referral Hospital
  • Mbale, Uganda
    • Mbale Regional referral Hospital
  • Mbarara, Uganda
    • Mbarara Regional referral Hospital
  • Mengo, Uganda
    • Mengo Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 95 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• De novo acute respiratory distress, as defined by dyspnea, use of accessory respiratory muscles, and a respiratory rate of 25 breaths per minute or more,
• Hypoxemia, as defined by a ratio of the partial pressure of arterial oxygen (PaO2) to the fraction of inspired oxygen (FiO2) of less than 300 mm Hg or a oxygen saturation by pulse oximetry SpO2/FiO2 ratio <315 will be considered for inclusion
• Informed consent obtained in accordance with local regulations;

Exclusion Criteria:

• Exacerbation of asthma, chronic obstructive pulmonary disease or another known or suspected chronic respiratory disease;
• Absolute contraindications to CPAP or HFNC
• Cardiac arrest; severe ventricular arrhythmia; shock defined by the need for vasopressors (dopamine > 5 microg/kg/min or adrenaline or noradrenaline at any dose)
• Altered consciousness (Coma Glasgow Score below 12 points);
• Do not intubate order, do not resuscitate order, or decision to limit full care taken before obtaining informed consent;
• Refusal to participate, prior enrolment in the trial, participation in another interventional study on respiratory distress;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High-flow oxygen nasal cannula (HFNC); In the high-flow-nasal cannula group, oxygen will be delivered through a heated humidifier and applied continuously through large-bore bi-nasal prongs, with a gas flow rate of 40-60 liters per minute and adjusted based on the clinical response.	Procedure: HFNC; 40-60l/min humidified oxygen by nasal cannula; Other Names: High-flow oxygen by nasal cannula
Experimental: Continuous positive airway pressure (CPAP); Patients assigned to the CPAP plus oxygen group will receive periods of CPAP in addition to the standard treatment. CPAP will be started at 7.5 cm of water. The level will be decreased to 5 cm of water or increased to 10 cm of water as needed based on the clinical response and tolerance.	Procedure: CPAP; Oxygen therapy by boussignac Continuous positive airway pressure face mask; Other Names: Continuous positive airway pressure
Active Comparator: Standard Low flow Oxygen Arm; Patients assigned to the standard treatment group will receive oxygen delivered through a Non-rebreather face mask until endotracheal intubation, death, or fulfillment of oxygen delivery cessation criteria (an oxygen saturation by pulse oximetry (SpO2) above 92% without oxygen and a respiratory rate below 25 cycles/min).	Procedure: Standard Oxygen; Oxygen therapy by low flow (upto 15l/min) by Non-rebreather face mask; Other Names: Standard Oxygen Therapy (low flow)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality	Number of study participants deceased at day 28 of study randomisation	28 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients intubated and ventilator-free	Number of patients intubated and ventilator-free at 28 days from randomisation	28 days
Patient Tolerance to CPAP or HFNC	Patients will be assessed using the Likert scale	7 days
Organ failure free days	Number of days from randomisation free of organ failure	7 days
Number of patients who meet criteria for intubation at day 7	Number of patients who meet criteria for intubation at day 7 of randomisation	7 days

Collaborators and Investigators

• Sponsor: Makerere University
• Collaborators: Wellcome Trust; Paris 12 Val de Marne University; THRiVE
• Investigators: Principal Investigator: Arthur Kwizera, MD, Makerere University

Study record dates

Study Major Dates

• Study Start (Actual): March 13, 2023
• Primary Completion (Actual): December 15, 2023
• Study Completion (Actual): January 16, 2024

Study Registration Dates

• First Submitted: December 6, 2020
• First Submitted That Met QC Criteria: December 31, 2020
• First Posted (Actual): January 5, 2021

Study Record Updates

• Last Update Posted (Estimated): May 15, 2024
• Last Update Submitted That Met QC Criteria: May 13, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Wounds and Injuries; Infant, Newborn, Diseases; Signs and Symptoms, Respiratory; Infant, Premature, Diseases; Thoracic Injuries; Respiratory Insufficiency; Hypoxia; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Lung Injury
• Other Study ID Numbers: ARISE_001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified data, upon reasonable request.
• IPD Sharing Time Frame: Upon study completion, in perpetuity.
• IPD Sharing Access Criteria: By email.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No