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Trial registered on ANZCTR

Registration number

ACTRN12621001000897

Ethics application status

Approved

Date submitted

24/02/2021

Date registered

30/07/2021

Date last updated

30/07/2021

Date data sharing statement initially provided

30/07/2021

Type of registration

Prospectively registered

Titles & IDs

Public title

Can Caffeine prevent the cessation of breathing in preterm newborn babies?

Scientific title

Comparing the prophylactic effects of Caffeine versus placebo on the apnea of prematurity in neonates of Kabul City: A randomized clinical trial

Secondary ID [1]

None

Universal Trial Number (UTN)

U1111-1265-3116

Trial acronym

PECAPNT

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Prematurity

Apnea of Prematurity

Low Birth Weight

Condition category

Condition code

Reproductive Health and Childbirth

Complications of newborn

Respiratory

Other respiratory disorders / diseases

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

65 preterm neonates in group A will manage by Caffeine citrate 20 mg/kg (2ml/kg) intravenously as the initial dose on the 1st day, and then 5 mg/kg (0.5ml/kg) intravenously daily as the maintenance dose for 10 days. The Caffeine citrate solution will be prepared as 10mg/ml by a pharmacist and coded by a statistician before the intervention. This coded solution would be administrated by a trained nurse under the observation of a Neonatologist.

Intervention code [1]

Prevention

Intervention code [2]

Treatment: Drugs

Comparator / control treatment

65 other preterm newborns in group B will take distilled water (2ml/kg) intravenously as the initial dose on the 1st day and then (0.5ml/kg) intravenously daily as the maintenance dose for 10 days. The solution of distilled water will be prepared and coded by a pharmacist and a statistician before the intervention. This coded solution would be administrated by a trained nurse under the observation of a Neonatologist.

Control group

Placebo

Outcomes

Primary outcome [1]

The risk of apnea is defined as a cessation of breathing for 20 seconds or longer or a shorter pause accompanied by bradycardia (heart rate less than 100 beats per minute), cyanosis, or low blood oxygen saturation. The apnea will be diagnosed and assessed by Cardio-respiratory Monitor.

Timepoint [1]

10days. The risk of apnea would be calculated from the number of preterm neonates with newly diagnosed apnea during 10days of intervention divided by the number of totals studied preterm neonates on this date.

Primary outcome [2]

The total duration of apnea attacks will be demonstrated in days. The duration of apnea attacks will be calculated from the starting day up to the ending day of apnea. The apnea would be assessed and diagnosed by Apnea Monitor or Cardio-pulmonary Monitor.

Timepoint [2]

The duration of apnea attacks will be calculated from the starting day up to the ending day of apnea. The observation period is 10days. The assessment and diagnosis of apnea would be done by Apnea Monitor or Cardio-pulmonary Monitor.

Primary outcome [3]

The frequency of apnea attacks in 24hr

Timepoint [3]

The neonates will be observed for 10days and the mean number of apnea in 24hrs would be obtained. The number of apnea in 24hrs will be monitored and assessed by an Apnea Monitor and a recording sheet.

Secondary outcome [1]

The risk of neonatal death during the intervention.

Timepoint [1]

10 days. The risk of neonatal death would be calculated from the number of dead preterm neonates during 10days of intervention divided by the number of totals studied preterm neonates on this date.

Eligibility

Key inclusion criteria

Neonates with the following criteria:
1. The gestational age of 34 weeks or less.
2. The birth weight less than 1500g.

Minimum age

1 Days

Maximum age

7 Days

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

Neonates with the following conditions:
1. Neonatal Meningitis diagnosed by CSF and complete blood count.
2. Neonatal Pneumonia diagnosed by infiltration on chest x-ray and complete blood count.
3. Visible CNS malformation.
4. Cyanotic Congenital Heart Diseases detected by echocardiography.
5. Hypoxic-ischemic encephalopathy detected by Levene or Sarnat-Sartant Scoring System.
6. Severe perinatal asphyxia diagnosed as an Apgar score less than 4.
7. Hypoglycemia or blood glucose level less than 40mg/dl.
8. Hypocalcemia or blood calcium level less than 7.5mg/dl.
9. Severe Anemia defined as hemoglobin less than 10g/dl
10. Intraventricular hemorrhage detected by ultrasonography.
11. Hyponatremia or serum sodium level less than 135mq/l
12. Hypernatremia or serum sodium level more than 145mq/l
13. Parents who declined the consents.

Study design

Purpose of the study

Prevention

Allocation to intervention

Randomised controlled trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

A list of randomized codes would be prepared for both products by a statistician, and the pharmacist will label the mentioned codes on the vials of Caffeine and distilled water. The vials will have a similar appearance. This will maintain concealment and double-blinded treatment allocation. After randomization, neither the patients nor the investigator or sponsor will be aware of the treatment allocation. Patients assigned to one of the double-blinded treatments will take the intravenous solution of Caffeine (10mg/ml) or distilled water. The involved statistician and pharmacists will be aware of the randomized treatment allocation sequence but they won’t involve in patient recruitment and keep the list and information concealed till the closure of the database.

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Permuted block randomization

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data

Intervention assignment

Parallel

Other design features

Phase

Phase 4

Type of endpoint/s

Efficacy

Statistical methods / analysis

Initially, raw data will collect in data collection sheets and then enter into SPSS software for statistical analysis. The efficacy of Caffeine citrate will assess by comparing the mean and risk ratio of data with the consideration of p-value. As we accepted the alpha errors of 0.05, therefore, the p-value less than 0.05 is significant.

Recruitment

Recruitment status

Not yet recruiting

Date of first participant enrolment

Anticipated

1/09/2021

Actual

Date of last participant enrolment

Anticipated

30/01/2023

Actual

Date of last data collection

Anticipated

28/02/2023

Actual

Sample size

Target

130

Accrual to date

Final

Recruitment outside Australia

Country [1]

Afghanistan

State/province [1]

Kabul

Funding & Sponsors

Funding source category [1]

University

Name [1]

Kabul University of Medical Science

Address [1]

Jamal Mena, Ataturk Avenue, 3rd district, 1003, Kabul.

Country [1]

Afghanistan

Primary sponsor type

Individual

Name

Mansoor Aslamzai

Address

Department of Neonatology, Maiwand Teaching Hospital, 1st district, 1001, Kabul.

Country

Afghanistan

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Research Committee of Ministry of Higher Education

Ethics committee address [1]

Ministry of Higher Education, 3rd district, 1003, Kabul.

Ethics committee country [1]

Afghanistan

Date submitted for ethics approval [1]

04/10/2020

Approval date [1]

03/02/2021

Ethics approval number [1]

letter no 664 date 3/2/2021

Summary

Brief summary

Introduction
The neonatal mortality rate in Afghanistan is one of the highest in the world and it was reported by UNICEF in 2019, 37 deaths per 1000 live births. Prematurity is one of the major causes (35%) of early neonatal mortality in Afghanistan. Preterm and low birth weight neonates encounter a lot of serious problems including apnea. Although apnea is an important cause of mortality and brain damage in immature babies, the prophylactic effect of Caffeine on the apnea of prematurity in newborn infants is revealed by a few studies with conflicting results
We Hypothesized that Caffeine citrate can prevent or decline the attacks of apnea in preterm neonates. Therefore we want to compare the prophylactic effects of Caffeine citrate versus placebo on the duration and daily attacks of apnea of prematurity in neonates with a gestational age of equal or less than 34 weeks or birth weight less than 1500g in Kabul hospitals. 
Research objectives: The primary objective is to compare the prophylactic effects of Caffeine citrate versus placebo on the duration and daily attacks of apnea of prematurity in neonates with a gestational age of equal or fewer than 34 weeks or birth weight less than 1500g in Kabul hospitals. The secondary objective is to evaluate the risk of neonatal death in both groups.
Research Hypothesis: Caffeine citrate can prevent or decline the attacks of apnea in preterm neonates with a gestational age of equal or fewer than 34 weeks or birth weight less than 1500g in Kabul hospitals. Caffeine citrate has a prophylactic effect on apnea in such neonates group.
Intervention: Totally,130 preterm neonates will be randomized to receive either Caffeine citrate (20mg/kg or 2ml/kg intravenously as the initial dose on the 1st day of life, and then 5 mg/kg or 0.5ml/kg intravenously daily as the maintenance dose for 10 days) or Placebo (distilled water 2ml/kg intravenously as the initial dose on the 1st day of life, and then(0.5ml/kg intravenously daily as the maintenance dose for 10 days) in this multisite, double-blind, controlled clinical trial.

Trial website

Trial related presentations / publications

Public notes

This study will find the prophylactic effects of Caffeine on the attacks of apnea in preterm babies with a gestational age of 34 weeks or less, or a birth weight of less than 1500gr in Kabul hospitals, Afghanistan. If the result of this research finds that Caffeine can decrease or prevent the attacks of apnea in preterm neonates, it will be suggested to policymakers to add Caffeine administration as a preventive measure in the management of such newborns. As apnea of prematurity may lead to hypoxia, multiple organ damage, and death; therefore, the prevention of apnea by Caffeine may decrease other complications, neonatal mortality, hospital stay, and extra charges. All of these are cost benefits to our government and people. In governmental and private hospitals, a lot of money and time spent due to the long management period of such an infant group. If needed, this study will come up with suggestions for further research studies.

Contacts

Principal investigator

Name

Prof Mansoor Aslamzai

Address

Department of Neonatology, Maiwand Teaching Hospital, 1st district, 1001 Kabul.

Country

Afghanistan

Phone

+93700603998

Fax

[email protected]

Contact person for public queries

Name

Mansoor Aslamzai

Address

Department of Neonatology, Maiwand Teaching Hospital, 1st district, 1001. Kabul.

Country

Afghanistan

Phone

+93700603998

Fax

[email protected]

Contact person for scientific queries

Name

Mansoor Aslamzai

Address

Department of Neonatology, Maiwand Teaching Hospital, 1st district, 1001, Kabul.

Country

Afghanistan

Phone

+93700603998

Fax

[email protected]

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

Yes

What data in particular will be shared?

individual participant data underlying published results only

When will data be available (start and end dates)?

Beginning 3 months and ending 5 years following main results publication

Available to whom?

case-by-case basis at the discretion of Primary Sponsor

Available for what types of analyses?

for IPD meta-analyses

How or where can data be obtained?

access subject to approvals by Principal Investigator: [email protected]

What supporting documents are/will be available?

Doc. No.	Type	Citation	Link	Email	Other Details	Attachment
10795	Study protocol			[email protected]		381494-(Uploaded-24-02-2021-16-13-33)-Study-related document.pdf

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Methylxanthine for the prevention and treatment of apnea in preterm infants.	2023	https://dx.doi.org/10.1002/14651858.CD013830.pub2

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Documents added manually

Documents added automatically