Clinical trial NCT03851783: Solar Oxygen Study
Official title: Effect of Solar Powered Oxygen Delivery on Childhood Mortality in Uganda: A Cluster-Randomized Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Pneumonia
Hypoxemia
Keywords: solar
oxygen
Lead sponsor: University of Alberta
Sponsor class: OTHER
Collaborators: name: Global Health Uganda LTD
First posted: 2019-02-22
Enrollment: 2405
Sex: ALL
Minimum age (years): 1
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Stepped-wedge cluster randomized controlled trial.
Primary purpose: TREATMENT

Brief summary: Globally, approximately 7.7 million children per year die before the age of 5 years. Infectious diseases account for a large proportion of these deaths, with pneumonia being the leading cause of mortality (2.1 million deaths/year). Most deaths occur in resource-poor settings in Asia and Africa. Oxygen (O2) therapy is essential to support life in these patients. Large gaps remain in the case management of children presenting to African hospitals with respiratory distress, including essential supportive therapies such as supplemental oxygen. In resource-constrained settings, oxygen delivery systems can lead to measurable improvements in survival from childhood pneumonia. A multihospital effectiveness study in Papua New Guinea demonstrated a reduction in mortality from childhood pneumonia from 5.0% to 3.2% (35% reduction in mortality) after implementation of enhanced oxygen delivery system. The investigators propose to investigate a novel strategy for oxygen delivery that could be implemented in remote locations with minimal access to an electrical power supply: solar-powered oxygen (SPO2).

Detailed description: Clinical features of pneumonia in children include fever, respiratory distress, and hypoxemia. Respiratory distress is a useful clinical summary description with good inter-observer consistency among experienced medical practitioners. The following clinical signs may indicate increased work of breathing: sustained nasal flaring; indrawing (recession) of the bony structures of the chest wall (subcostal, intercostal, supraclavicular) on inspiration; tracheal tug; and deep breathing (acidotic or Kussmaul breathing). Respiratory distress is a sign that one or more serious pathological processes are at play: metabolic acidosis, fluid overload, acute lung injury, and/or co-morbid pneumonitis. Respiratory distress, together with alteration of consciousness, is a strong predictor of mortality in children with severe febrile illness in sub-Saharan Africa. The grim prognostic significance of respiratory distress applies to several disease states, irrespective of microbial etiology, including malaria as well as non-malaria febrile illness.

Arterial hypoxemia in pneumonia results from several mechanisms: pulmonary arterial blood flow to consolidated lung resulting in an intrapulmonary shunt, intrapulmonary oxygen consumption, and ventilation-perfusion mismatch. Hypoxemia is a risk factor for mortality in pediatric pneumonia, and was associated with a 5-fold increased risk of death in studies from Kenya and Gambia. In one report from Nepal, the prevalence of hypoxemia (SpO2 \< 90%) in 150 children with pneumonia was 39% overall, with increasing rates of hypoxemia across strata of pneumonia severity (100% of very severe, 80% of severe and 17% of pneumonia patients). General features of respiratory distress were associated with hypoxemia in this study, including chest indrawing, lethargy, grunting, nasal flaring, cyanosis, inability to breastfeed or drink.

Oxygen is a lifesaving therapy for children with pneumonia and hypoxemia; however, challenges remain in oxygen delivery globally. Two main systems of oxygen delivery have been implemented and evaluated in resource-constrained settings, oxygen cylinders and oxygen concentrators. Oxygen cylinders are ready to use, simple to operate and do not require any electricity. However, cylinders are very costly and distribution and use is challenging. Oxygen concentrators have proven to be an effective means of delivering oxygen and are significantly less expensive that cylinders. However, oxygen concentrators require continuous and reliable electricity to operate which is not readily available in many regions, particularly in resource-limited settings where the majority of pneumonia deaths occur. In order to meet the demand for oxygen therapy in resource-limited settings, the investigators developed a novel strategy for oxygen delivery: solar-powered oxygen (SPO2). This system uses free inputs (sun and air) and could be implemented in remote locations with minimal access to an electrical power supply. Our group is the first to conduct rigorous scientific trials of SPO2.

To date, the investigators have accumulated substantial clinical experience with SPO2, having treated \>150 hypoxemic children, over several years, at two Ugandan hospitals. Compared to other oxygen delivery methods, SPO2 is superior. SPO2 is more reliable than oxygen concentrators connected to grid electricity, because it is not affected by frequent power outages. SPO2 utilizes a renewable, sustainable and freely available source of energy. SPO2 is more reliable than compressed oxygen cylinders, which are frequently out of stock in the public hospital system. SPO2 is more user-friendly and safer for nurses than cylinders, which require physical strength to change regulators on high-pressure cylinders. SPO2 is less wasteful than cylinders, which tend to leak through ill-fitting regulators under real-world conditions.

The study is a multi-centre prospective evaluation of SPO2. The investigators will use a stepped-wedge cluster-randomized design to allow for robust scientific conclusions about the efficacy of SPO2. Importantly, demonstration of a mortality benefit of SPO2 will provide strong supportive evidence and could catalyse the widespread implementation of SPO2 in resource-limited settings across Africa and Asia.

Eligibility criteria: Inclusion Criteria:

1. Age under 5 years
2. Hypoxemia (SpO2\<92%) based on non-invasive pulse oximetry
3. Hospital admission warranted based on clinician judgment

Exclusion Criteria:

1. SpO2 ≥92%
2. Outpatient management
3. Denial of consent to participate in study

Primary outcomes:
measure: Mortality
timeFrame: 48 hours
Secondary outcomes:
measure: In hospital mortality
timeFrame: Until end of hospitalization (usually 3 to 7 days)
measure: Length of hospital stay
timeFrame: Until end of hospitalization (usually 3 to 7 days)
measure: Oxygen saturation
timeFrame: Until end of hospitalization (usually 3 to 7 days)
measure: Oxygen delivery system failure
timeFrame: Until end of trial (24 months)
measure: Total costs of implementing solar-powered oxygen delivery systems
timeFrame: Until end of trial (24 months)
Other outcomes:
Locations:
city: Adumi
country: Uganda
facility: Adumi Health Centre IV
city: Apac
country: Uganda
facility: Apac District Hospital
city: Atiak
country: Uganda
facility: Atiak Health Centre IV
city: Bugobero
country: Uganda
facility: Bugobero Health Centre IV
city: Bukedea
country: Uganda
facility: Bukedea Health Centre IV
city: Bumanya
country: Uganda
facility: Bumanya Health Centre IV
city: Bundibugyo
country: Uganda
facility: Bundibugyo Hospital
city: Kagadi
country: Uganda
facility: Kagadi Hospital
city: Kalisizo
country: Uganda
facility: Kalisizo Hospital
city: Kamuli
country: Uganda
facility: Kamuli General Hospital
city: Kayunga
country: Uganda
facility: Kayunga District Hospital
city: Kidera
country: Uganda
facility: Kidera Health Centre IV
city: Kitagata
country: Uganda
facility: Kitagata Hospital
city: Kitgum
country: Uganda
facility: Kitgum General Hospital
city: Kyenjojo
country: Uganda
facility: Kyenjojo General Hospital
city: Lalogi
country: Uganda
facility: Lalogi Health Centre IV
city: Lyantonde
country: Uganda
facility: Lyantonde Hospital
city: Mpigi
country: Uganda
facility: Gombe Hospital
city: Muyembe
country: Uganda
facility: Muyembe Health Centre IV
city: Sembabule
country: Uganda
facility: Sembabule Health Centre IV
Study officials:
affiliation: University of Alberta
name: Michael T Hawkes, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Makerere University/Global Health Uganda
name: Robert O Opoka, MBChB, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Turnbull H, Conroy A, Opoka RO, Namasopo S, Kain KC, Hawkes M. Solar-powered oxygen delivery: proof of concept. Int J Tuberc Lung Dis. 2016 May;20(5):696-703. doi: 10.5588/ijtld.15.0796.
citation: Hawkes MT, Conroy AL, Namasopo S, Bhargava R, Kain KC, Mian Q, Opoka RO. Solar-Powered Oxygen Delivery in Low-Resource Settings: A Randomized Clinical Noninferiority Trial. JAMA Pediatr. 2018 Jul 1;172(7):694-696. doi: 10.1001/jamapediatrics.2018.0228.
citation: Conradi N, Mian Q, Namasopo S, Conroy AL, Hermann LL, Olaro C, Amone J, Opoka RO, Hawkes MT. Solar-powered oxygen delivery for the treatment of children with hypoxemia: protocol for a cluster-randomized stepped-wedge controlled trial in Uganda. Trials. 2019 Dec 5;20(1):679. doi: 10.1186/s13063-019-3752-2.