## Protocol Section
### Identification Module
**NCT ID:** NCT06422000

**Brief Title:** Effect of Pentoxifylline Versus Probiotic on Preterm Neonates With Necrotizing Enterocolitis

**Official Title:** Pentoxifylline Versus Probiotic as Adjuvant Therapy for Preterm Neonates With Necrotizing Enterocolitis

#### Organization Study ID Info
**ID:** pentoxifylline probiotic NEC
#### Organization
**Class:** OTHER
**Full Name:** Tanta University
### Status Module
#### Completion Date
**Date:** 2023-12-30

**Type:** ACTUAL

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-20

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-14

**Overall Status:** COMPLETED

#### Primary Completion Date
**Date:** 2023-11-01

**Type:** ACTUAL

#### Start Date
**Date:** 2022-06-30

**Type:** ACTUAL

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-20
**Type:** ACTUAL
**Study First Submit Date:** 2022-11-11
**Study First Submit QC Date:** 2024-05-14
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Tanta University

#### Responsible Party

**Investigator Affiliation:** Tanta University

**Investigator Full Name:** Alaa Mohamed Ahmed Rowisha

**Investigator Title:** clinical pharmacist

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

### Description Module

**Brief Summary:** The aim of this study is to evaluate the effectiveness of pentoxifylline versus probiotics supplementation as adjuvant therapy for preterm neonates with necrotizing enterocolitis.

**Detailed Description:** This randomized clinical trial includes 75 preterm infants who met the inclusion criteria for stage I and stage II NEC. Patients are allocated randomly into three groups (each included 25 neonates); group I (traditional therapy group) received antibiotics according to culture and sensitivity results, group II (pentoxifylline group) received antibiotics and IV pentoxifylline at a dose of 30 mg/ Kg given over 6 hours daily until discharge from the unit, and group III (probiotics group) received antibiotics and probiotics sachets supplementation in a dose of 100 mg mixed with 10 ml sterile water and given by Ryle tube once daily until discharge. The serum level of high-mobility group box protein 1 (HMGB-1), intestinal fatty acid binding proteins (I-FABP), and total antioxidant capacity (TAC) were measured on admission and at discharge.

### Conditions Module

**Conditions:**

- Necrotizing Enterocolitis

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 75

**Type:** ACTUAL

**Phases:**

- PHASE3

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** will include 25 preterm neonates with NEC who will receive traditional therapy of NEC including antibiotics and normal incubator care measures

**Label:** control group (group I)

**Type:** NO_INTERVENTION

#### Arm Group 2

**Description:** will include 25 preterm neonates with NEC who will receive traditional therapy of NEC in association with IV pentoxifylline at a dose of 30 mg/kg given over 6 hours daily (Schüller et al., 2020) until discharge from the unit after clinical and laboratory improvement .

**Intervention Names:**

- Drug: Pentoxifylline

**Label:** pentoxifylline group (group II)

**Type:** ACTIVE_COMPARATOR

#### Arm Group 3

**Description:** will include 25 preterm neonates with NEC who will receive traditional therapy of NEC in association with probiotics sachets supplementation, in the form of lyophilized lactic acid bacteria each Aluminium stick pack contains 100 mg ( Meyer et al., 2020) Probio Tec BB12-Blend 30- IF\* (SANDOZ®.) mixed with 10 ml sterile water and given by Ryle tube once daily until discharge from the unit after clinical and laboratory improvement .

**Intervention Names:**

- Drug: Probiotic Formula

**Label:** probiotic group (group III)

**Type:** ACTIVE_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- pentoxifylline group (group II)

**Description:** Pentoxifylline 30 mg/kg given over 6 hours daily

**Name:** Pentoxifylline

**Other Names:**

- group 2 (Pentoxifylline group)

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- probiotic group (group III)

**Description:** probiotics sachets supplementation, in the form of lyophilized lactic acid bacteria each Aluminium stick pack contains 100 mg ( Meyer et al., 2020) Probio Tec BB12-Blend 30- IF\* (SANDOZ®.) mixed with 10 ml sterile water and given by Ryle tube once daily until discharge from the unit after clinical and laboratory improvement .

**Name:** Probiotic Formula

**Other Names:**

- group 3 (Probiotic group)

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** record mortality rate in each group during treatment

**Measure:** Mortality rate

**Time Frame:** 2 months

**Description:** record any complications or side effects of the treating drugs

**Measure:** complications and side effects

**Time Frame:** 2 months

**Description:** Change in serum C-reactive protein at baseline and after 2 months

**Measure:** Inflammatory parameter

**Time Frame:** 2 months

#### Secondary Outcomes

**Description:** blood sample will be collected at baseline and after 2 months

**Measure:** change in serum high-mobility group box protein 1 (HMGB1)

**Time Frame:** 2 months

**Description:** blood sample will be collected at baseline and after 2 months

**Measure:** change in serum Intestinal fatty acid binding protein (I-FABP).

**Time Frame:** 2 months

**Description:** Blood sample will be collected at baseline and after 2 months

**Measure:** change in serum total antioxidant capacity (TAC)

**Time Frame:** 2 months

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Male and female preterm neonates less than 37 weeks gestational age
* Suffering from necrotizing enterocolitis (NEC), according to Modified Bell's system which was first proposed by Bell et al., 1978 as stage I (suspected), II (proven) .
* Diagnosis of NEC depends on; history, physical examination, laboratory and radiographic findings .
* Signs and symptoms of NEC (at least three or more ), including; unstable temperature, apnea, increased residual milk in stomach, mid abdominal distension, vomiting coffee-like substances, bloody stool
* Laboratory findings including; thrombocytopenia, hypernatremia, metabolic acidosis, neutropenia and leukocytosis.
* Anterior posterior abdominal radiograph is used for diagnosis in which pneomatosis intestinalis in stage II NEC

Exclusion Criteria:

* Term and post term neonates
* Neonates with congenital infections
* Neonates with major congenital anomalies
* Neonates with stage III NEC

**Maximum Age:** 37 Weeks

**Sex:** ALL

**Standard Ages:**

- CHILD

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Tanta

**Country:** Egypt

**Facility:** Tanta University

**State:** El Gharbia

#### Overall Officials

**Official 1:**

**Affiliation:** professor and head of clinical pharmacy department, faculty of Pharmact, Tanta University, Egypt

**Name:** Sahar Hegazy, MD

**Role:** STUDY_DIRECTOR

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000005759

- Term: Gastroenteritis

- ID: D000005767

- Term: Gastrointestinal Diseases

- ID: D000004066

- Term: Digestive System Diseases

- ID: D000007410

- Term: Intestinal Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BXS

- Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions

- Abbrev: All

- Name: All Conditions

- Abbrev: BC06

- Name: Digestive System Diseases

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M25869

- Name: Premature Birth

- Relevance: LOW

- As Found: Unknown

- ID: M7922

- Name: Enterocolitis

- Relevance: HIGH

- As Found: Enterocolitis

- ID: M22151

- Name: Enterocolitis, Necrotizing

- Relevance: HIGH

- As Found: Necrotizing Enterocolitis

- ID: M8875

- Name: Gastroenteritis

- Relevance: LOW

- As Found: Unknown

- ID: M8883

- Name: Gastrointestinal Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M7255

- Name: Digestive System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M10444

- Name: Intestinal Diseases

- Relevance: LOW

- As Found: Unknown

- ID: T4055

- Name: Necrotizing Enterocolitis

- Relevance: HIGH

- As Found: Necrotizing Enterocolitis

### Condition Browse Module - Meshes

- ID: D000004760

- Term: Enterocolitis

- ID: D000020345

- Term: Enterocolitis, Necrotizing

### Intervention Browse Module - Ancestors

- ID: D000010726

- Term: Phosphodiesterase Inhibitors

- ID: D000004791

- Term: Enzyme Inhibitors

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

- ID: D000010975

- Term: Platelet Aggregation Inhibitors

- ID: D000011837

- Term: Radiation-Protective Agents

- ID: D000020011

- Term: Protective Agents

- ID: D000045505

- Term: Physiological Effects of Drugs

- ID: D000014665

- Term: Vasodilator Agents

- ID: D000016166

- Term: Free Radical Scavengers

- ID: D000000975

- Term: Antioxidants

### Intervention Browse Module - Browse Branches

- Abbrev: Infe

- Name: Anti-Infective Agents

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: VaDiAg

- Name: Vasodilator Agents

- Abbrev: PlAggInh

- Name: Platelet Aggregation Inhibitors

- Abbrev: Ot

- Name: Other Dietary Supplements

### Intervention Browse Module - Browse Leaves

- ID: M4222

- Name: Anti-Bacterial Agents

- Relevance: LOW

- As Found: Unknown

- ID: M13342

- Name: Pentoxifylline

- Relevance: HIGH

- As Found: Manufacturer

- ID: M4224

- Name: Antibiotics, Antitubercular

- Relevance: LOW

- As Found: Unknown

- ID: M13629

- Name: Phosphodiesterase Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M7951

- Name: Enzyme Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M13865

- Name: Platelet Aggregation Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M21869

- Name: Protective Agents

- Relevance: LOW

- As Found: Unknown

- ID: M14684

- Name: Radiation-Protective Agents

- Relevance: LOW

- As Found: Unknown

- ID: M17412

- Name: Vasodilator Agents

- Relevance: LOW

- As Found: Unknown

- ID: M4292

- Name: Antioxidants

- Relevance: LOW

- As Found: Unknown

- ID: T355

- Name: Acidophilus

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000010431

- Term: Pentoxifylline

### Misc Info Module

- Version Holder: 2024-05-31
