ANZCTR - Registration

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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]

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

Condition category

Condition code

Reproductive Health and Childbirth

Complications of newborn

Oral and Gastrointestinal

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]

Treatment: Drugs

Comparator / control treatment

Equal volume of placebo (normal saline).

Control group

Placebo

Outcomes

Primary outcome [1]

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]

Primary outcome will be from the time of diagnosis of NEC till discharge or death

Secondary outcome [1]

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]

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?

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

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

Funding & Sponsors

Funding source category [1]

Charities/Societies/Foundations

Name [1]

Raine Foundation

Address [1]

Department of Neonatal Paediatrics, 374 Bagot road, Subiaco, PeRth, WA 6008

Country [1]

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]

Individual

Name [1]

Sanjay Patole

Address [1]

none

Country [1]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Women's and children's health Services

Ethics committee address [1]

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

Approval date [1]

28/03/2006

Ethics approval number [1]

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

Prof Sanjay Patole

Address

Department of Neonatal Paediatrics, KEM Hospital for Women, 374 Bagot Road, Subiaco, Perth, WA 6008

Country

Armenia

Phone

+61893401260

Fax

[email protected]

Contact person for public queries

Name

Sanjay Patole

Address

Neonatal Paediatrics, KEM Hospital for Women, Perth, WA 6008

Country

Australia

Phone

08-93401260

Fax

08-93401266

[email protected]

Contact person for scientific queries

Name

Sanjay Patole

Address

Neonatal Paediatrics KEM Hospital for Women Perth WA 6008

Country

Australia

Phone

08-93401260

Fax

08-93401266

[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

Source	Title	Year of Publication	DOI
Embase	Pentoxifylline for treatment of sepsis and necrotising enterocolitis in neonates.	2023	https://dx.doi.org/10.1002/14651858.CD004205.pub4

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

Trial Review

Documents added manually

Documents added automatically