Ignite Creation Date:
2024-05-05 @ 5:26 PM
Last Modification Date:
2024-10-26 @ 9:31 AM
Study NCT ID:
NCT00455468
Status:
COMPLETED
Last Update Posted:
2011-07-12
First Post:
2007-04-01
Brief Title:
Randomized Controlled Trial RCT in Children With Severe Pneumonia
Sponsor:
International Centre for Diarrhoeal Disease Research Bangladesh
Organization:
International Centre for Diarrhoeal Disease Research Bangladesh
Study Overview
Official Title:
None
Status:
COMPLETED
Status Verified Date:
2007-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Pneumonia is the leading cause of childhood morbidity and death in many developing countries including Bangladesh causing about 2 million deaths worldwide each year Pneumonia is an infection of the lungs most commonly caused by viruses or bacteria like Streptococcus pneumoniae and Haemophilus influenzae Depending on the clinical presentation pneumonia can be classified as very severe severe or non-severe with specific treatment for each of them except for antibiotic therapy Severe and very severe pneumonia require hospitalization for additional supportive treatment such as suction oxygen therapy and administration of bronchodilator In Bangladesh the number of hospital beds is inadequate for admission of all pneumonia cases that require hospitalization however it is also important to provide institutional care to those children who cannot be hospitalized due to bed constraints Provision of appropriate antibiotics and supportive cares during the period of stay at established day-care centres could be an effective alternative The impetus for this study came from the findings of our recently completed study titled Daycare-based management of severe pneumonia in under-5 children when hospitalization is not possible due to the lack of beds This study successfully managed children n251 but it was not a randomized trial and thus direct comparison of the efficacy of management of severe pneumonia at the day-care centre essential for building confidence for implementing this management policy is not possible We the researchers at the International Centre for Diarrhoeal Disease Research Bangladesh could not plan a randomized controlled trial RCT because of ethical reasons Now that we have data suggesting effectiveness as well as safety of the day-care based treatment for management of children with severe pneumonia a RCT should be possible Two hundred fifty-one children with severe pneumonia were enrolled at the Radda Clinic from June 2003 to May 2005 The mean age was 77 2-55 months 86 infants 63 boys and 91 breast-fed History of cough was present in 99 cases fever in 89 and rapid breathing in 67 cases Forty-four percent of children were febrile 38C 93 children had vesicular breath sound and 99 bilateral rales Fifty-seven percent of children were hypoxic with mean oxygen saturation of 934 which was corrected by oxygen therapy 983 Eighty percent of children had severe pneumonia and 20 had very severe pneumonia The mean duration of clinic stay was 72 days Two hundred thirty-four 93 children completed the study successfully 11 44 referred to hospitals only one participant had to visit hospital at night due to deterioration of his condition 9 were referred to hospital at the time of clinic closure ie at 5 pm and one participant was referred to hospital during the morning hours and 6 24 left against medical advice LAMA There was no death during the period of clinic stay but only four 16 deaths occurred during the 3 months follow-up The study indicated that treatment of severe pneumonia in children at the day-care centre is effective and safe and thus it is comparable to the hospital care If the day-care based management is found to have comparable efficacy to that of hospitalized management of severe pneumonia in children then they could be managed at outpatient day-care set ups reducing hospitalization and thus freeing beds for management of other children who need hospitalized care Additionally availability of the treatment facility in community set-ups will be cost and time saving for the population Children of either sex aged 2-59 months attending the Radda Clinic and Institute of Child Health and Shishu Hospital ICHSH with severe pneumonia will be randomized to receive either the day-care management at the clinic or hospitalized management at the ICHSH Children randomized to receive day-care treatment will stay at the clinic from 8 am-5 pm and will receive antibiotics and other supportive cares At 5 pm they would be send to respective homes with advice to bring back their children to the clinic next morning and advised to provide other supports at home The same management would be continued till improvement and discharged and followed up every 2 weeks for 3 months Children randomized to receive hospitalized management would be admitted at ICHSH and receive standard treatment like antibiotics and other supportive cares The same treatment would be continued for 24 hoursday rather than 9 hoursday at the day-care clinic till improvement and discharged and followed-up at the ICHSH every 2 weeks for 3 months About 3000 children with pneumonia visit Radda Clinic each year and about 200 of them will have severe pneumonia requiring hospitalization Thus we hope to enroll 368 184 in each site children with severe pneumonia during a 2-year study period
Detailed Description:
Acute lower respiratory infection ALRI particularly pneumonia is the leading cause of childhood morbidity and death in the developing countries including Bangladesh Acute respiratory infection ARI causes more than 2 million child deaths worldwide each year most of these deaths are due to pneumonia and 90 of them occur in less-developed countries Recent estimates suggest that 19 million 95 CI 16-22 million children died from ARI throughout the world in 2000 and 70 of them occurred in Africa and Southeast Asia ARI is also a major cause of visits to the outpatient and emergency departments as well as admissions to the hospitals Although bronchiolitis tracheobronchitis and pneumonia each accounts for about one-third of ALRI cases pneumonia is responsible for most ALRI deaths Three studies that reported diagnoses in children who died of ALRI revealed that a median of 89 range 71 to 100 of ALRI deaths were associated with pneumonia In Bangladesh ALRI accounts for 25 of under-5 children deaths and 40 of infantile deaths In a study conducted at the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research Bangladesh ICDDRB in 1986-88 among 401 under-5 children with ALRI it has been observed that the most common manifestation was pneumonia and a respiratory pathogen both bacterial and viral was identified in 30 cases The case fatality rates were 14 in bacterial pneumonia and 3 in viral pneumonia Bacterial infections play a major role as a cause of pneumonia in children in developing countries Pooled data from lung aspiration studies mostly from developing countries reported 52-62 isolation rates of bacteria The case-fatality rate in severe ALRI in children aged 1-4 years is 10-15 times higher in the developing than in the developed countries It is an infection of the lungs most commonly caused by viruses or bacteria It is usually not possible to determine the specific cause of pneumonia by either clinical or chest X-ray features In children Streptococcus pneumoniae and Haemophilus influenzae are the two most important bacterial pathogens Respiratory Syncytial Virus RSV is also an important cause of ARI among preschool children Emerging evidence suggests that Mycoplasma pneumoniae and Chlamydia pneumoniae may cause pneumonia among older children Available data also suggests that mixed viral and bacterial infections are common in children in developing countries which need to be treated with antibiotics More recently data from a large vaccine trial suggested Streptococcus pneumoniae to play a major role in the development of pneumonia associated with viral infections The WHO recommendations for treatment of pneumonia are based on data that Streptococcus pneumoniae and Haemophilus influenzae are the most common causes of bacterial pneumonia in developing countries Depending on clinical presentation pneumonia can be classified as very severe severe or non-severe with specific treatment guidelines available for each of them The WHO defines very severe pneumonia as clinical symptoms and signs of pneumonia cough or difficulty breathing with one or more danger signs like cyanosis convulsions drowsiness stridor in calm child or inability to drink all signifying hypoxaemia or severe respiratory distress and severe clinical malnutrition Severe pneumonia is defined as cough or difficulty breathing with lower chest wall in drawing with or without fast breathing defined as the respiratory rate 50 breaths per minute for children aged 2-11 months and 40 breaths per minute for children aged 12-59 months Lower chest wall in drawing is defined as inward movement of the bony structures of the lower chest wall with inspiration observed while the child is at rest Finally non-severe pneumonia is defined as cough or difficulty breathing with fast breathing as defined earlier Antibiotic therapy is indicated irrespective of the severity of pneumonia Proper management of children presenting in health centres and hospitals with respiratory symptoms is the cornerstone of acute respiratory infection control To address the high mortality associated with ALRI WHO launched a programme for control of ARI with the major objective to reduce the child mortality and to promote rational use of antibiotic Current standard ARI case management recommends that children with cough and normal breathing be treated as outpatients without any antibiotics assuming viral infection or mild bacterial infections those with rapid respiration tachypnoea indicating lower respiratory infection or pneumonia be treated with an antibiotic on an ambulatory basis non-severe pneumonia while those with chest wall in drawing indicative of severe pneumonia be admitted to hospital and treated with parenteral antibiotics and supportive cares Vaccination against measles pertussis Haemophilus influenzae type b Hib and Streptococcus pneumoniae can help decrease the incidence and lessen the severity of respiratory infections However newer vaccines against respiratory infections such as Hib and pneumococcal conjugate vaccines are not widely available in developing countries Under-5 children with respiratory symptoms are brought to the general practitioners as well as to primary health care facilities for treatment At these respective places the health care providers are required to differentiate between acute upper respiratory infections AURI and acute lower respiratory infections ALRIpneumonia and categorize severity of pneumonia taking into consideration the nutritional status of the patients and provide either ambulatory therapy or refer patients for hospitalization as appropriate
Severe and very severe pneumonia require hospitalization for additional supportive treatment like oro or nasopharyngeal suction when indicated using a suction device oxygen therapy to hypoxic children bronchodilators to patients with bronchospasm bronchodilatation by nebulizer if the patients fulfill the criteria for nebulization and fluid and nutritional management and close monitoring In Bangladesh the number of hospital beds are inadequate for admission of all pneumonia cases that fulfill the criteria for hospitalization Hospitalization may also not be possible for inability of the parents to visit a hospital due to distance or financial reasons despite appropriate referral However it is also important to provide institutional care to those children who cannot be hospitalized at least until stabilization of their acute conditions If such children are sent home with antibiotics it would be important to establish an expensive home follow up system without which a significant proportion of them would be expected to have a fatal outcome Provision of broad-spectrum antibiotics and appropriate supportive care during the period of stay at established day-care centres could be an effective alternative To examine this possibility we have recently completed a study entitled Daycare-based management of severe pneumonia in under-5 children when hospitalization is not possible due to the lack of beds ICDDRB Protocol No 2002-036 at the Radda MCH-FP Centre located in Mirpur Section-10 Dhaka Bangladesh The estimated catchment population of the Radda Clinic is about 15 million The hypothesis of our recently completed study was that it would be possible to provide effective treatment and care to under-5 children with severe pneumonia at a day-care clinic set up and if so the need for hospitalization could be significantly reduced The study examined if children who required hospitalization according to WHO guidelines but were not hospitalized due to any reason could be managed at a day-care facility modified primary care set up which is important to reduce morbidity and more importantly deaths among such children We are impressed with the results which suggested that this model of management is effective 251 children with severe pneumonia were enrolled at the Radda Clinic from June 2003 to May 2005 The mean age was 77 2-55 months 86 were infants 63 boys and 91 breast-fed On admission history of cough was present in 99 cases fever in 89 rapid breathing in 67 and difficulty in breathing in 33 cases On examination 44 children were febrile 38C 97 children had tachypnoea with respiratory rate 50 per minute and 98 had lower chest wall in drawing On auscultation 93 children had vesicular breath sound and 99 bilateral rales Most children were well nourished but 57 were hypoxic with mean oxygen saturation of 934 on admission which was corrected by oxygen therapy 983 According to WHO criteria 80 children had severe pneumonia and 20 had very severe pneumonia The mean duration of clinic stay was 72 days 234 93 children completed the study successfully without any problem 11 44 referred to hospitals only one participant had to visit hospital at night due to deterioration of his condition 9 were referred to hospital at the time of clinic closure ie at 5 pm and one participant was referred to hospital during the morning hours and 6 24 left against medical advice LAMA There was no death during the period of clinic stay but only four 16 deaths occurred during the 3 months follow-up period after discharge from the clinic This study indicated that treatment of severe pneumonia in children at the day-care centre is effective and safe and thus it is comparable to the hospital care Although this study successfully managed all children n251 but it was not a randomized trial and thus direct comparison of the effectiveness of management of severe pneumonia at the day-care centre essential to recommend implementation of this management policy is not possible We could not plan for a RCT due to ethical reasons for our recently completed day-care pneumonia study Now that we have data suggesting effectiveness as well as safety of the day-care based treatment and care of under-5 children with severe pneumonia a RCT would now be possible In the proposed study we would identify under-5 children attending the outpatient department of the Radda Clinic and ICHSH with severe pneumonia and randomize them in equal numbers for management at the day-care centre Radda Clinic or hospital ICHSH subject to consent of respective parentsguardians Children with very severe pneumonia who needs hospitalization would not be enrolled as they need hospital care and it would be unethical at this stage to enroll them in the proposed study About 3000 children with a clinical diagnosis of pneumonia visit the clinic each year and we estimate that about 200 of them will have severe pneumonia requiring hospitalization - the patient population of our study We hope to enroll requisite 368 184site children with severe pneumonia during 2-year study period
Severe and very severe pneumonia require hospitalization for additional supportive treatment like oro or nasopharyngeal suction when indicated using a suction device oxygen therapy to hypoxic children bronchodilators to patients with bronchospasm bronchodilatation by nebulizer if the patients fulfill the criteria for nebulization and fluid and nutritional management and close monitoring In Bangladesh the number of hospital beds are inadequate for admission of all pneumonia cases that fulfill the criteria for hospitalization Hospitalization may also not be possible for inability of the parents to visit a hospital due to distance or financial reasons despite appropriate referral However it is also important to provide institutional care to those children who cannot be hospitalized at least until stabilization of their acute conditions If such children are sent home with antibiotics it would be important to establish an expensive home follow up system without which a significant proportion of them would be expected to have a fatal outcome Provision of broad-spectrum antibiotics and appropriate supportive care during the period of stay at established day-care centres could be an effective alternative To examine this possibility we have recently completed a study entitled Daycare-based management of severe pneumonia in under-5 children when hospitalization is not possible due to the lack of beds ICDDRB Protocol No 2002-036 at the Radda MCH-FP Centre located in Mirpur Section-10 Dhaka Bangladesh The estimated catchment population of the Radda Clinic is about 15 million The hypothesis of our recently completed study was that it would be possible to provide effective treatment and care to under-5 children with severe pneumonia at a day-care clinic set up and if so the need for hospitalization could be significantly reduced The study examined if children who required hospitalization according to WHO guidelines but were not hospitalized due to any reason could be managed at a day-care facility modified primary care set up which is important to reduce morbidity and more importantly deaths among such children We are impressed with the results which suggested that this model of management is effective 251 children with severe pneumonia were enrolled at the Radda Clinic from June 2003 to May 2005 The mean age was 77 2-55 months 86 were infants 63 boys and 91 breast-fed On admission history of cough was present in 99 cases fever in 89 rapid breathing in 67 and difficulty in breathing in 33 cases On examination 44 children were febrile 38C 97 children had tachypnoea with respiratory rate 50 per minute and 98 had lower chest wall in drawing On auscultation 93 children had vesicular breath sound and 99 bilateral rales Most children were well nourished but 57 were hypoxic with mean oxygen saturation of 934 on admission which was corrected by oxygen therapy 983 According to WHO criteria 80 children had severe pneumonia and 20 had very severe pneumonia The mean duration of clinic stay was 72 days 234 93 children completed the study successfully without any problem 11 44 referred to hospitals only one participant had to visit hospital at night due to deterioration of his condition 9 were referred to hospital at the time of clinic closure ie at 5 pm and one participant was referred to hospital during the morning hours and 6 24 left against medical advice LAMA There was no death during the period of clinic stay but only four 16 deaths occurred during the 3 months follow-up period after discharge from the clinic This study indicated that treatment of severe pneumonia in children at the day-care centre is effective and safe and thus it is comparable to the hospital care Although this study successfully managed all children n251 but it was not a randomized trial and thus direct comparison of the effectiveness of management of severe pneumonia at the day-care centre essential to recommend implementation of this management policy is not possible We could not plan for a RCT due to ethical reasons for our recently completed day-care pneumonia study Now that we have data suggesting effectiveness as well as safety of the day-care based treatment and care of under-5 children with severe pneumonia a RCT would now be possible In the proposed study we would identify under-5 children attending the outpatient department of the Radda Clinic and ICHSH with severe pneumonia and randomize them in equal numbers for management at the day-care centre Radda Clinic or hospital ICHSH subject to consent of respective parentsguardians Children with very severe pneumonia who needs hospitalization would not be enrolled as they need hospital care and it would be unethical at this stage to enroll them in the proposed study About 3000 children with a clinical diagnosis of pneumonia visit the clinic each year and we estimate that about 200 of them will have severe pneumonia requiring hospitalization - the patient population of our study We hope to enroll requisite 368 184site children with severe pneumonia during 2-year study period
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None