Clinical trial NCT04693403: Adult Respiratory Failure Intervention Study Africa
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Acute Respiratory Failure With Hypoxia
Acute Respiratory Distress Syndrome
Acute Lung Injury
Lead sponsor: Makerere University
Sponsor class: OTHER
Collaborators: name: THRiVE
name: Paris 12 Val de Marne University
name: Wellcome Trust
First posted: 2021-01-05
Enrollment: 705
Sex: ALL
Minimum age (years): 18
Maximum age (years): 95
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Stepped wedge cluster randomised trial (8 Clusters).
Primary purpose: TREATMENT

Brief summary: 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?

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.

Eligibility criteria: 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;

Primary outcomes:
measure: Mortality
timeFrame: 28 day
Secondary outcomes:
measure: Number of patients intubated and ventilator-free
timeFrame: 28 days
measure: Patient Tolerance to CPAP or HFNC
timeFrame: 7 days
measure: Organ failure free days
timeFrame: 7 days
measure: Number of patients who meet criteria for intubation at day 7
timeFrame: 7 days
Other outcomes:
Locations:
city: Entebbe
country: Uganda
facility: Entebbe Regional Referral Hospital
city: Gulu
country: Uganda
facility: St Mary's, Lacor
city: Hoima
country: Uganda
facility: Hoima Regional referral Hospital
city: Jinja
country: Uganda
facility: Jinja Regional Referral Hospital
city: Kabale
country: Uganda
facility: Kabale Regional Referral Hospital
city: Kampala
country: Uganda
facility: Mulago National Specialised Hospital
city: Kampala
country: Uganda
facility: Kampala hospital
city: Kampala
country: Uganda
facility: Kiruddu National referral Hospital
city: Kampala
country: Uganda
facility: Naguru Referral Hospital
city: Kampala
country: Uganda
facility: Nsambya Hospital
city: Kampala
country: Uganda
facility: Rubaga Hospital
city: Kampala
country: Uganda
facility: TMR International Hospital
city: Kisoro
country: Uganda
facility: Kisoro District Hospital
city: Masaka
country: Uganda
facility: Masaka regional Referral Hospital
city: Mbale
country: Uganda
facility: Mbale Regional referral Hospital
city: Mbarara
country: Uganda
facility: Mbarara Regional referral Hospital
city: Mengo
country: Uganda
facility: Mengo Hospital
Study officials:
affiliation: Makerere University
name: Arthur Kwizera, MD
role: PRINCIPAL_INVESTIGATOR
References: