CPAP Improving Mortality for Pneumonia in African Children Trial

NCT02484183 | Terminated DMC

• 1 other identifier: IRB00055734
• Study Type: interventional
• Target: 646
• Locations: 1 country
• Sites: 1

Brief Summary

Pneumonia mortality rates in African countries like Malawi are high and increased further in children -exposed or infected with human immunodeficiency virus (HIV) as well as those that are severely malnourished or severely hypoxemic. Treatment innovations are needed. Bubble continuous positive airway pressure (bCPAP) improves oxygenation and ventilation and is a simple, relatively inexpensive adaptation of conventional continuous positive airway pressure potentially suitable for low-resource settings. bCPAP has been demonstrated to improve outcomes in neonates less than 1 month of age. Recently, a limited number of hospitals are using bCPAP to escalate pneumonia care for older African children failing standard treatment with antibiotics and oxygen. Supportive evidence for this approach is observational only. Quality randomized studies comparing bCPAP versus a standard-of-care control group that includes low-flow oxygen therapy and using a primary endpoint of mortality are not available in low-resource settings including high prevalence HIV countries like Malawi. Demonstrating a mortality benefit with bCPAP is needed to support further investment and scale up of bCPAP in the care of older Malawian children 1-59 months of age with World Health Organization (WHO) severe pneumonia complicated by HIV and/or malnutrition or severe hypoxemia. With the full support of the Malawi Ministry of Health and in collaboration with external experts from Lilongwe Medical Relief Trust and Cincinnati Children's Hospital Medical Center investigators plan to address this critical evidence gap by conducting a randomized controlled study determining bCPAP outcomes, compared to the currently recommended standard of care endorsed by the WHO and Malawi national pneumonia guidelines, in hospitalized Malawian children with WHO-defined severe pneumonia complicated by a co-morbidity ((1) HIV-infection, (2) HIV-exposure without infection, (3) severely malnourished) or WHO pneumonia with severe hypoxemia and without a co-morbidity. The investigators hypothesize that bCPAP will reduce the mortality of Malawian children with WHO-defined severe pneumonia.

Conditions

Pneumonia; Human Immunodeficiency Virus (HIV); Malnutrition; Hypoxemia

Keywords

bubble continuous positive airway pressure (CPAP); pneumonia; Human Immunodeficiency Virus (HIV); malnutrition; Malawi; Africa; Noninvasive Ventilation; child; pediatric; hypoxemia

Outcome Measures

Primary Outcomes (1)

• Pneumonia mortality

  Proportion of in-hospital death in children with World Health Organization (WHO) severe pneumonia.

  Participants followed for duration of hospital stay, an expected average of 7 days

Secondary Outcomes (3)

• Post-discharge mortality

  30 days after hospital discharge.

• Relapse

  30 days

• Treatment failure

  14 days

Study Arms (2)

Low-flow oxygen

NO INTERVENTION

Low-flow oxygen supplementation if respiratory danger signs are present or if their oxygen saturation is \<90%. Respiratory danger signs include any of the following: grunting, severe chest indrawing, very fast breathing (\>70 breaths/minute if 1-11 months; \>60 breaths/minute if 12-59 months), nasal flaring, stridor in a calm child, or apnea. Low-flow oxygen given by an oxygen concentrator with a nasal cannula. Low-flow is 0.5 liters per minute (LPM) for patients 1-2 months, and 1-2 LPM for patients 2-59 months. For 2-59 month olds oxygen can be increased to a maximum of 2 LPM to maintain a 90% saturation or treat respiratory danger signs.

bubble CPAP

EXPERIMENTAL

Bubble continuous positive airway pressure (bCPAP) patients are eligible if respiratory danger signs are present or if oxygen saturation is \<90%. bCPAP will be initiated at 7 centimeters (cm) water (H20) if 1-2 months of age or 8cm H20 if 2-59 months of age using the minimum oxygen flow necessary to achieve these pressures. Gradual weaning can be attempted after 24-48 hours of treatment. All changes will be followed by 60 minutes of monitoring.

Device: bubble continuous positive airway pressure (CPAP)

Interventions

bubble continuous positive airway pressure (CPAP) DEVICE

This study will use an Airsep® oxygen concentrator and a Fisher \& Paykel Bubble CPAP (bCPAP) system to deliver bCPAP. The Airsep® machine is connected to the Fischer \& Paykel Bubble CPAP system and the CPAP delivers pressure and oxygen to the patient with appropriately sized masks and tubing. The Fischer \& Paykel Bubble CPAP system can deliver up to 10 centimeters (cm) water (H20) pressure. Since an oxygen concentrator is being used as the flow driver of this bubble CPAP system patients receiving CPAP will therefore also be receiving 6-8 liters per minute (LPM) of concentrated oxygen flow. Per manufacturer specifications the Airsep oxygen concentrator delivers 90-97% fractional inspired oxygen concentration at the 6-8 LPM flows required to generate 4-10 cm H20 pressure.

Also known as: Fisher and Paykel

bubble CPAP

Eligibility Criteria

• Age: 1 Month - 59 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Meets World Health Organization (WHO) severe pneumonia criteria and is either Human Immunodeficiency Virus (HIV)-infected, HIV-exposed, severely malnourished, or has severe hypoxemia without HIV-infection, HIV-exposure, or severe malnutrition.

You may not qualify if:

• Any psychosocial condition or circumstance that, in the opinion of the investigators, would interfere with the conduct of the study. Prior participation in the study during a previous pneumonia diagnosis.

Sponsors & Collaborators

• Johns Hopkins University: lead
• University of North Carolina, Chapel Hill: collaborator
• Ministry of Health and Population, Malawi: collaborator
• Children's Hospital Medical Center, Cincinnati: collaborator
• University of Utah: collaborator

Study Sites (1)

Salima District Hospital

Salima, Malawi

Location

Related Publications (4)

• Sessions KL, Ruegsegger L, Mvalo T, Kondowe D, Tsidya M, Hosseinipour MC, Lufesi N, Eckerle M, Smith AG, McCollum ED. Focus group discussions on low-flow oxygen and bubble CPAP treatments among mothers of young children in Malawi: a CPAP IMPACT substudy. BMJ Open. 2020 May 12;10(5):e034545. doi: 10.1136/bmjopen-2019-034545.

  PMID: 32404389 DERIVED

• McCollum ED, Mvalo T, Eckerle M, Smith AG, Kondowe D, Makonokaya D, Vaidya D, Billioux V, Chalira A, Lufesi N, Mofolo I, Hosseinipour M. Bubble continuous positive airway pressure for children with high-risk conditions and severe pneumonia in Malawi: an open label, randomised, controlled trial. Lancet Respir Med. 2019 Nov;7(11):964-974. doi: 10.1016/S2213-2600(19)30243-7. Epub 2019 Sep 24.

  PMID: 31562059 DERIVED

• Sessions KL, Mvalo T, Kondowe D, Makonokaya D, Hosseinipour MC, Chalira A, Lufesi N, Eckerle M, Smith AG, McCollum ED. Bubble CPAP and oxygen for child pneumonia care in Malawi: a CPAP IMPACT time motion study. BMC Health Serv Res. 2019 Jul 31;19(1):533. doi: 10.1186/s12913-019-4364-y.

  PMID: 31366394 DERIVED

• Smith AG, Eckerle M, Mvalo T, Weir B, Martinson F, Chalira A, Lufesi N, Mofolo I, Hosseinipour M, McCollum ED. CPAP IMPACT: a protocol for a randomised trial of bubble continuous positive airway pressure versus standard care for high-risk children with severe pneumonia using adaptive design methods. BMJ Open Respir Res. 2017 Jun 30;4(1):e000195. doi: 10.1136/bmjresp-2017-000195. eCollection 2017.

  PMID: 28883928 DERIVED

MeSH Terms

Conditions

Pneumonia; Acquired Immunodeficiency Syndrome; Malnutrition; Hypoxia

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Lung Diseases; Respiratory Tract Diseases; HIV Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Nutrition Disorders; Nutritional and Metabolic Diseases; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Eric D McCollum, MD

  Johns Hopkins School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 23, 2015
• First Posted: June 29, 2015
• Study Start: June 23, 2015
• Primary Completion: April 28, 2018
• Study Completion: April 28, 2018
• Last Updated: May 3, 2018

Record last verified: 2018-05

Data Sharing

• IPD Sharing: Will share

Locations

MA (1)