Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12606000257561
Ethics application status
Approved
Date submitted
21/06/2006
Date registered
27/06/2006
Date last updated
5/01/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
Pentoxifylline as a secondary prophylaxis for necrotising enterocolitis in preterm neonates
Scientific title
Safety and efficacy of pentoxifylline as a treatment for preventing the progression of necrotising enterocolitis in preterm neonates– A randomised, placebo controlled pilot trial
Secondary ID [1] 288247 0
Nil known
Universal Trial Number (UTN)
'Nil known'
Trial acronym
POINT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Necrotising enterocolitis 1234 0
Condition category
Condition code
Reproductive Health and Childbirth 1318 1318 0 0
Complications of newborn
Oral and Gastrointestinal 1319 1319 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Enrolled neonates will be allocated to an intravenous infusion of either pentoxifylline at 5mg/kg/hour for 12 hours a day (60mg/kg/day) for 2 consecutive days. The duration of the infusion would then be reduced to 6 hours a day (30mg/kg/day) for the next 4 consecutive days. The total duration of treatment will thus be 6 days or shorter in case of stoppage due to any significant adverse drug reaction/s. The study drug solution (5mg/ml) will be infused at 1ml/kg/hour.
Intervention code [1] 1148 0
Treatment: Drugs
Comparator / control treatment
Equal volume of placebo (normal saline).
Control group
Placebo

Outcomes
Primary outcome [1] 1804 0
Safety and efficacy of pentoxifylline in preventing the progression of NEC from at or greater than Stage II to Stage III and /or death
Timepoint [1] 1804 0
Primary outcome will be from the time of diagnosis of NEC till discharge or death
Secondary outcome [1] 3161 0
Secondary outcomes will include reduction in plasma tumor necrosis factor (TNF)- alpha levels, the extent of bowel resection at surgery, duration of hospital stay and total parenteral nutrition (TPN) support, and time to full enteral feeds (150ml/kg/day).
Timepoint [1] 3161 0
Blood samples (0.5mL) will be collected for measurement of circulating TNF-alpha levels prior to the commencement of the pentoxifylline infusion, at 48 hours after completion of the high dose infusion and on day 6 after completing therapy.

Eligibility
Key inclusion criteria
(1) Preterm neonates with at or greater than Stage II (definite) NEC will be eligible for enrolment as soon as the diagnosis is made and (2) Informed parental consent is obtained and (3) At least one cranial ultrasound has been performed prior to the diagnosis of NEC as routine surveillance for IVH or any other intracranial pathology.
Minimum age
Not stated
Maximum age
32 Weeks
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
(1) Failure to obtain informed parental consent (2) Presence of major congenital malformation/s (3) Presence of chromosomal aberrations (4) Presence of *hepatic impairment (Elevated serum aminotransaminase, alkaline phosphatase, and/or ammonia levels to >2.5 times the normal in presence of prolonged prothrombin and partial thromboplastin time) (5) Presence of *renal impairment (Blood urea nitrogen > 30 mg/dl, urine output <0.6 ml/kg/hour for at least 6 hours, and creatinine > 0.8 mg/dL) *Normal values (ALT: 3-54 U/L, AST: 10-65 U/L, Alkaline phosphatase: 110-400 U/L, Ammonia: 20-80 ?g/dL) and definitions of hepatic and renal impairment: Ref: Appendix A and D: 732-3 In Manual of Neonatal Care, Fifth Edition 2004, Eds: Cloherty JP, Eichenwald EC, Stark AR.

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)
identical placebo ampoules, on line randomisation, all investigators blinded
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
special software program will perform randomisation electronically online using computor generated random numbers
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2 / Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Withdrawn
Reason for early stopping/withdrawal
Date of first participant enrolment
Anticipated
15/09/2006
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
80
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 1443 0
Charities/Societies/Foundations
Name [1] 1443 0
Raine Foundation
Country [1] 1443 0
Australia
Primary sponsor type
Hospital
Name
KEM Hospital for Women, Perth
Address
374 Bagot Road, Subiaco, Western Australia 6008
Country
Australia
Secondary sponsor category [1] 1277 0
Individual
Name [1] 1277 0
Sanjay Patole
Address [1] 1277 0
none
Country [1] 1277 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 2818 0
Women's and children's health Services
Ethics committee address [1] 2818 0
Ethics committee country [1] 2818 0
Australia
Date submitted for ethics approval [1] 2818 0
Approval date [1] 2818 0
28/03/2006
Ethics approval number [1] 2818 0
1232/EW

Summary
Brief summary
HYPOTHESIS: Pentoxifylline may be beneficial as a specific secondary prophylaxis for necrotising enterocolitis (NEC) in preterm neonates. AIM: To evaluate the safety and efficacy of pentoxifylline as a secondary prophylaxis for preventing progression of NEC in preterm neonates in a randomised, placebo-controlled pilot trial. BACKGROUND: NEC is the most common neonatal gastrointestinal emergency. NEC related mortality (20-40%) and morbidity including long-term neurodevelopmental impairment and the socioeconomic burden continue to be high. Despite extensive research the pathogenesis of NEC remains poorly understood. No single specific strategy exists for either prevention or treatment of NEC. Pentoxifylline is a non-steroidal anti-inflammatory agent with diverse immunomodulatory properties including inhibition of TNF alpha- an important pro-inflammatory cytokine implicated in the pathogenesis of NEC. It has been shown to significantly reduce the incidence and severity of NEC in an experimental trial. PATIENTS AND METHODS: Eligibility criteria: Preterm neonates (gestation: <32 weeks) with definite (equal to or greater than Stage II) NEC will be eligible for enrolment after the diagnosis of the illness is made and informed parental consent is obtained. Exclusion criteria: (1) Failure to obtain informed parental consent (2) Presence of congenital malformation/s (3) Presence of chromosomal aberrations (4) Presence of hepatic or renal impairment (5) Exposure to pentoxifylline within 1 week prior to enrolment. Randomisation, allocation, blinding: The Coordinating Pharmacist (CP) will supply the medication packs containing either the placebo or pentoxifylline, identified only by a number designating the allocation. Only the supplier and the CP will be aware of the allocation. A software program written for the trial will perform randomisation. The electronic online randomisation will be stratified by neonatal gestational age (up to 27 weeks and at /above 28 weeks) within each participating center to ensure that the smallest and sickest neonates would be equally distributed between pentoxifylline and placebo groups. Pentoxifylline and placebo (normal saline) solutions have identical appearance and will be supplied in identical looking ampoules. The parents and all study personnel including the statisticians will be masked to the allocation status. Drug protocol: Enrolled neonates will be allocated to an IV infusion of either pentoxifylline or an equal volume of placebo at 5mg/kg/hour for 12 hours a day (60mg/kg/day) for 2 consecutive days, followed by infusion for 6 hours a day (30mg/kg/day) for the next 4 consecutive days. Statistical considerations: The estimated sample size for the pilot trial is 80 (Pentoxifylline: 40, Placebo: 40). Pentoxifylline safety will be assessed by analysing the adverse events in the first 30 neonates allocated to the drug. Guidelines for monitoring and analysing adverse events are provided. The results will help in determining the feasibility and sample size of a large definitive trial. Subgroup: A subgroup analyses is planned for neonates with gestational age up to 27 weeks given that the mortality and morbidity including long term neurodevelopmental impairment related to NEC is significantly higher in them. Primary and secondary outcomes: The primary outcome would be the safety and efficacy of pentoxifylline in reducing the progression of NEC from at or greater than Stage II to Stage III and/or death. Adverse events of interest will include systemic hypotension and intraventricular hemorrhage. The secondary outcomes will include the duration of hospital stay and TPN support, and the time to full enteral feeds (150 ml/kg/day) after NEC. OUTCOMES AND SIGNIFICANCE: Our research has the potential for providing a simple strategy for preventing progression of NEC in preterm neonates that is associated with significant mortality and morbidity including long-term neurodevelopmental impairment.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 35787 0
Prof Sanjay Patole
Address 35787 0
Department of Neonatal Paediatrics, KEM Hospital for Women, 374 Bagot Road, Subiaco, Perth, WA 6008
Country 35787 0
Armenia
Phone 35787 0
+61893401260
Fax 35787 0
Email 35787 0
[email protected]
Contact person for public queries
Name 10337 0
Sanjay Patole
Address 10337 0
Neonatal Paediatrics, KEM Hospital for Women, Perth, WA 6008
Country 10337 0
Australia
Phone 10337 0
08-93401260
Fax 10337 0
08-93401266
Email 10337 0
[email protected]
Contact person for scientific queries
Name 1265 0
Sanjay Patole
Address 1265 0
Neonatal Paediatrics KEM Hospital for Women Perth WA 6008
Country 1265 0
Australia
Phone 1265 0
08-93401260
Fax 1265 0
08-93401266
Email 1265 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbasePentoxifylline for treatment of sepsis and necrotising enterocolitis in neonates.2023https://dx.doi.org/10.1002/14651858.CD004205.pub4
N.B. These documents automatically identified may not have been verified by the study sponsor.