Measurement and evaluation of the clinical response (return of spontaneous respiration within 3 minutes of naloxone administration) to a new nasal naloxone formulation in opioid poisonings in the pediatric Emergency Department.
Design
Clinical randomized, non-inferiority, parallel-group, phase 1-2 trial on 40 patients. Randomization was centralized and computerized with concealed randomization sequences carried out at an external website.
Settings and conduct
The pediatrics department of Loghman-Hakim Hospital Poison Center is the only center for pediatric toxicology in Tehran (Iran). In this trial, 40 opioid poisoned patients were randomized 1:1 to receive naloxone hydrochloride, either intranasally (1.4mg/0.1ml) or IV (0.8 mg) with escalating dose of 0.1 mg/kg naloxone hydrochloride IV if it doesn't respond). Supportive care or oxygenation will be administered simultaneously in accordance with existing clinical protocol. Due to the nature of the study blinding was not possible.
Participants/Inclusion and exclusion criteria
All pediatric opioid-poisoned patients who were referred with clinical and laboratory confirmation of opioid poisoning, and did not take the antidote and had no IV line access.
Intervention groups
Opioid-poisoned children were randomized 1:1 to receive naloxone hydrochloride, either intranasally (1.4mg/0.1ml) or IV (0.8 mg) with an escalating dose of 0.1 mg/kg naloxone hydrochloride IV if it doesn't respond). and underwent under close monitoring.
Main outcome variables
The proportion of patients with a return of spontaneous respiration (above the minimum respiratory rate in each age group per minute) within 3 minutes of naloxone administration would be the primary outcome.
General information
Reason for update
Acronym
IRCT registration information
IRCT registration number:IRCT20120629010133N7
Registration date:2023-06-06, 1402/03/16
Registration timing:retrospective
Last update:2023-06-06, 1402/03/16
Update count:0
Registration date
2023-06-06, 1402/03/16
Registrant information
Name
Hossein Hassanian-Moghaddam
Name of organization / entity
Shahid Beheshti University of Medical Sciences
Country
Iran (Islamic Republic of)
Phone
+98 21 5542 4041
Email address
hassanian@sbmu.ac.ir
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2021-01-16, 1399/10/27
Expected recruitment end date
2023-04-16, 1402/01/27
Actual recruitment start date
2023-04-16, 1402/01/27
Actual recruitment end date
2023-04-16, 1402/01/27
Trial completion date
2023-04-16, 1402/01/27
Scientific title
Intranasal versus intravenous administration of naloxone in pediatric opioid poisoned patients, A pilot randomized clinical trial
Public title
The efficacy of intranasal naloxone in pediatric opioid overdose patients
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
Age more than 1 and less than 12
Opioid poisoning
Respiratory depression
Miotic pupils
Unarousable as defined by Glasgow Coma Score (GCS) ≤ 12/15
Exclusion criteria:
Still conscious on ED arrival time
Patients that have received naloxone in any form in the previous 24 hours
Referral cases with unknown drug intervention
Patients who have been referred with IV access
Presentation with apnea
Nasal congestion
No parental deferred consent provided
GCS < 7/15
History of drug hypersensitivity relevant to naloxone
Co-ingestion of other drugs
Intubation before recruitment
major facial trauma
Epistaxis
Negative urine screening test for opioids
A clinical condition (such as abnormal liver function; respiratory, renal or cardiac issues) which, in the opinion of the examining medical practitioner, makes participation in the study inappropriate.
Age
From 1 year old to 12 years old
Gender
Both
Phase
1-2
Groups that have been masked
No information
Sample size
Target sample size:
40
Actual sample size reached:
40
Randomization (investigator's opinion)
Randomized
Randomization description
The allocation sequence was generated in one session by the PI (who was not involved in treating patients) through a random digit generator website, and the PI stored the randomization list in a locked cabinet.
Blinding (investigator's opinion)
Not blinded
Blinding description
Placebo
Not used
Assignment
Parallel
Other design features
Secondary Ids
1
Registry name
WHO Universal Trial Number
Secondary trial Id
U1111-1260-5747
Registration date
2020-11-02, 1399/08/12
Ethics committees
1
Ethics committee
Name of ethics committee
Ethics committee of Shahid Behehsti University of Medical Sciences
Street address
Buiding no 2, Shahid Beheshti University of medical Sciences, Arabi St, Yaman St, Tehran
Poisoning by narcotics and psychodysleptics [hallucinogens]
Primary outcomes
1
Description
Proportion of patients with return of spontaneous respiration (above minimum respiratory rate in each age group per minute)
Timepoint
On arrival and within 3 minutes of naloxone administration, then each 4 hours
Method of measurement
Measuring the number of respiration in a minute
Secondary outcomes
1
Description
Time it takes to place IV cannula
Timepoint
From start of procedure till the end (ready for intravenous use)
Method of measurement
Measured by stopwatch (per second)
2
Description
Level of consciousness
Timepoint
Before intervention, 3 minute after intervention, then each 4--hour
Method of measurement
Using Glascow Coma Scale
3
Description
O2 saturation before and after naloxone administration
Timepoint
Before intervention, 3 minute after intervention, then each 4--hour
Method of measurement
Using pulse oxymeter
4
Description
Increased pCO2
Timepoint
Before intervention, 3 minute after intervention, then each 4--hour
Method of measurement
Using blood gas machine
5
Description
Need for a rescue opioid antidote in ED and afterward
Timepoint
During ED admission or afterward till discharge
Method of measurement
Record each dose naloxone, route of administration and time given during admission
Intervention groups
1
Description
Intervention group:
Category
Treatment - Drugs
Recruitment centers
1
Recruitment center
Name of recruitment center
Loghman Hakim Hospital
Full name of responsible person
Narges Gholami
Street address
Kamali Ave, Sout Karegar Street
City
Tehran
Province
Tehran
Postal code
1333635445
Phone
+98 21 5540 9534
Email
hasanian2000@yahoo.com
Sponsors / Funding sources
1
Sponsor
Name of organization / entity
Shahid Beheshti University of Medical Sciences
Full name of responsible person
Afshin Zarghi
Street address
Building no 2, Arabi St, Yaman St
City
Tehran
Province
Tehran
Postal code
1985717443
Phone
+98 21 2243 9788
Email
zarghi@sbmu.ac.ir
Grant name
Comparison of intranasal versus intravenous administration of naloxone in improvement of loss of conscious, respiratory rate and oxygen saturation in pediatric opioid poisoned patients, A pilot randomized clinical trial
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
No
Title of funding source
DNE pharma
Proportion provided by this source
20
Public or private sector
Private
Domestic or foreign origin
Foreign
Category of foreign source of funding
Sponsor: country of origin
Country of origin
NO
Type of organization providing the funding
Industry
Person responsible for general inquiries
Contact
Name of organization / entity
Shahid Beheshti University of Medical Sciences
Full name of responsible person
Hossein Hassanian-Moghaddam
Position
Associate Professor
Latest degree
Subspecialist
Other areas of specialty/work
Addiction Medicine,
Street address
Shohada-e-Tajrish hospital, Tajrish Square
City
Tehran
Province
Tehran
Postal code
1989934148
Phone
+98 21 2274 9201
Email
hassanian@sbmu.ac.ir
Person responsible for scientific inquiries
Contact
Name of organization / entity
Shahid Beheshti University of Medical Sciences
Full name of responsible person
Hossein Hassanian Moghaddam
Position
Associate Professor
Latest degree
Subspecialist
Other areas of specialty/work
Toxicology
Street address
Shohada-e-Tajrish Hospital, Tajrish Square
City
Tehran
Province
Tehran
Postal code
1989934148
Phone
+98 21 2271 9016
Email
hassanian@sbmu.ac.ir
Person responsible for updating data
Contact
Name of organization / entity
Shahid Beheshti University of Medical Sciences
Full name of responsible person
Narges Gholami
Position
Associate Professor
Latest degree
Specialist
Other areas of specialty/work
Pediatrics
Street address
Pediatric ward, Loghman Hakim Hospital, Kamali Ave, south karegar, tehran
City
Tehran
Province
Tehran
Postal code
1333635445
Phone
+98 21 5102 5000
Email
nargesgholami724@yahoo.com
Sharing plan
Deidentified Individual Participant Data Set (IPD)
No - There is not a plan to make this available
Justification/reason for indecision/not sharing IPD
There is no further information
Study Protocol
Yes - There is a plan to make this available
Statistical Analysis Plan
Yes - There is a plan to make this available
Informed Consent Form
Undecided - It is not yet known if there will be a plan to make this available
Clinical Study Report
Undecided - It is not yet known if there will be a plan to make this available
Analytic Code
Undecided - It is not yet known if there will be a plan to make this available
Data Dictionary
Undecided - It is not yet known if there will be a plan to make this available
Title and more details about the data/document
Part of the collected deidentified IPD for the primary outcome measure only
When the data will become available and for how long
There is no further information
To whom data/document is available
Only available for people working in academic institutions
Under which criteria data/document could be used
Only by written request and subject to considering the right of authors
From where data/document is obtainable
By email to the corresponding author
What processes are involved for a request to access data/document
Determination of exact data and an explanation for possible contribution