## Protocol Section
### Identification Module
**NCT ID:** NCT00133679

**Brief Title:** Chronic Sildenafil for Severe Diaphragmatic Hernia

**Official Title:** Chronic Sildenafil for Severe Diaphragmatic Hernia

#### Organization Study ID Info
**ID:** K23HL079922-01
**Link:** https://reporter.nih.gov/quickSearch/K23HL079922-01
**Type:** NIH
#### Organization
**Class:** OTHER
**Full Name:** University of California, San Francisco
### Status Module
#### Completion Date
**Date:** 2013-10

**Type:** ACTUAL

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2021-01-13

**Type:** ACTUAL

**Last Update Submit Date:** 2021-01-12

**Overall Status:** TERMINATED

#### Primary Completion Date
**Date:** 2013-07

**Type:** ACTUAL

#### Results First Post Date
**Date:** 2021-01-13

**Type:** ACTUAL

**Results First Submit Date:** 2020-12-07

**Results First Submit QC Date:** 2021-01-12

#### Start Date
**Date:** 2006-02

**Status Verified Date:** 2021-01

#### Study First Post Date
**Date:** 2005-08-23
**Type:** ESTIMATED
**Study First Submit Date:** 2005-08-22
**Study First Submit QC Date:** 2005-08-22
**Why Stopped:** Change in clinical practice allowing chronic therapy at 6 weeks of age, incompatible with possibility of placebo beyond 6 weeks of age on study protocol
### Sponsor Collaborators Module

#### Collaborators

**Class:** OTHER

**Name:** Children's Hospital Los Angeles

**Class:** OTHER

**Name:** Ann & Robert H Lurie Children's Hospital of Chicago

#### Lead Sponsor

**Class:** OTHER

**Name:** University of California, San Francisco

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Oversight Has DMC:** True

### Description Module

**Brief Summary:** The purpose of this study is to test if sildenafil is effective in the treatment of infants with severe congenital diaphragmatic hernia (determined by the presence of prolonged pulmonary hypertension or prolonged oxygen supplementation on mechanical ventilation), as measured by the estimated pulmonary artery systolic pressure following treatment.

**Detailed Description:** Congenital diaphragmatic hernia (CDH) is a condition characterized by pulmonary parenchymal and vascular hypoplasia. Severe CDH carries a high rate of mortality, and significant morbidity among survivors. This proposal is a randomized, blinded, placebo-controlled study designed to evaluate the efficacy and potential mechanisms of activity of sildenafil, a phosphodiesterase-5 inhibitor, for treatment of severe CDH. Infants who meet criteria at ≥10d of age predicting a poor outcome \[death or chronic lung disease (CLD) severe enough to require hospital discharge on supplemental oxygen (O2)\] will be eligible for the study. Infants whose parents consent for the study will undergo an initial echocardiogram to assess the degree of pulmonary hypertension. They will then begin either sildenafil or placebo therapy for a 45d course. A final echocardiogram will be performed after the experimental drug course is completed. The pulmonary arterial systolic pressure estimate during hyperoxic conditions will be compared between the sildenafil and placebo groups. Infants from either group who have severely elevated pulmonary arterial pressure (despite supplemental O2) will be considered for open-label sildenafil, which will continue after hospital discharge, depending on the results of a cardiac catheterization performed for clinical care.

### Conditions Module

**Conditions:**

- Hernia, Diaphragmatic

- Hypertension, Pulmonary

- Hypoplasia, Pulmonary

**Keywords:**

- Chronic lung disease

- Nitric oxide

- cyclic guanosine monophosphate

- phosphodiesterase inhibitor

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** QUADRUPLE

**Who Masked:**

- PARTICIPANT

- CARE_PROVIDER

- INVESTIGATOR

- OUTCOMES_ASSESSOR

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 9

**Type:** ACTUAL

**Phases:**

- PHASE4

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Sildenafil x 45 days

**Intervention Names:**

- Drug: sildenafil

**Label:** 1

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** Placebo x 45 d

**Intervention Names:**

- Drug: Placebo

**Label:** 2

**Type:** PLACEBO_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- 1

**Description:** Sildenafil 0.5 mg/kg every 6 hours orally x 45 d

**Name:** sildenafil

**Other Names:**

- Viagra, Revatio

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- 2

**Description:** Placebo suspension (equal volume to experimental drug) x 45 days

**Name:** Placebo

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Measure:** Estimated Systolic Pulmonary Arterial Pressure at Final Echocardiogram

**Time Frame:** 7 weeks

#### Secondary Outcomes

**Measure:** Systemic Levels of Vasoactive Substances at the Time of Final Echocardiogram

**Time Frame:** 7 weeks

**Measure:** Adverse Effects of Sildenafil Therapy

**Time Frame:** 2 years

**Measure:** Somatic Growth at 1 and 2 Years of Age

**Time Frame:** 2 years

**Measure:** Neurodevelopmental Outcome at 1 and 2 Years of Age

**Time Frame:** 2 years

**Measure:** Respiratory Status at 1 and 2 Years of Age

**Time Frame:** 2 years

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Congenital diaphragmatic hernia
* 10-42 days (d) of age
* Significant illness severity as demonstrated by:
* Receiving assisted ventilation and

  * FiO2 \>= 0.40 at 10-14d of age, or
  * FiO2 \>= 0.40 for \>=48hours at 15-27d of age, or
  * FiO2 \>= 0.35 at 28-42d of age
* Or, need for extracorporeal support at \>=10d of age
* Or, estimated pulmonary arterial or right ventricular systolic pressure of \>= 2/3 systemic pressure at 14-42d of age

Exclusion Criteria:

* Structural congenital heart disease (other than patent ductus arteriosus or patent foramen ovale/atrial septal defect \[ASD\] or non-hemodynamically significant ventricular septal defect \[VSD\])
* Sildenafil contraindicated (until condition resolves):

  * Unable to absorb oral medication, or
  * Unstable systemic blood pressure, or
  * Receiving a drug that may interfere with sildenafil metabolism, or
  * Renal insufficiency
  * Hepatic insufficiency Previous use of sildenafil

**Maximum Age:** 42 Days

**Minimum Age:** 10 Days

**Sex:** ALL

**Standard Ages:**

- CHILD

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Los Angeles

**Country:** United States

**Facility:** Children's Hospital of Los Angeles

**State:** California

**Zip:** 90027

**Location 2:**

**City:** San Francisco

**Country:** United States

**Facility:** University of California San Francisco Children's Hospital

**State:** California

**Zip:** 94143

**Location 3:**

**City:** Chicago

**Country:** United States

**Facility:** Children's Memorial Hospital

**State:** Illinois

**Zip:** 60614

#### Overall Officials

**Official 1:**

**Affiliation:** University of California, San Francisco

**Name:** Roberta L Keller, MD

**Role:** PRINCIPAL_INVESTIGATOR

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000006973

- Term: Hypertension

- ID: D000014652

- Term: Vascular Diseases

- ID: D000002318

- Term: Cardiovascular Diseases

- ID: D000020763

- Term: Pathological Conditions, Anatomical

- ID: D000082122

- Term: Internal Hernia

- ID: D000000013

- Term: Congenital Abnormalities

- ID: D000008171

- Term: Lung Diseases

- ID: D000012140

- Term: Respiratory Tract Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC14

- Name: Heart and Blood Diseases

- Abbrev: All

- Name: All Conditions

- Abbrev: BC08

- Name: Respiratory Tract (Lung and Bronchial) Diseases

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: BC16

- Name: Diseases and Abnormalities at or Before Birth

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M10024

- Name: Hypertension

- Relevance: LOW

- As Found: Unknown

- ID: M11168

- Name: Lung Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M9625

- Name: Hernia

- Relevance: HIGH

- As Found: Hernia

- ID: M10027

- Name: Hypertension, Pulmonary

- Relevance: HIGH

- As Found: Hypertension, Pulmonary

- ID: M30544

- Name: Hernias, Diaphragmatic, Congenital

- Relevance: HIGH

- As Found: Diaphragmatic Hernia

- ID: M9626

- Name: Hernia, Diaphragmatic

- Relevance: HIGH

- As Found: Hernia, Diaphragmatic

- ID: M17400

- Name: Vascular Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M22519

- Name: Pathological Conditions, Anatomical

- Relevance: LOW

- As Found: Unknown

- ID: M2344

- Name: Internal Hernia

- Relevance: LOW

- As Found: Unknown

- ID: M25675

- Name: Hernia, Abdominal

- Relevance: LOW

- As Found: Unknown

- ID: M12

- Name: Congenital Abnormalities

- Relevance: LOW

- As Found: Unknown

- ID: M14977

- Name: Respiratory Tract Diseases

- Relevance: LOW

- As Found: Unknown

- ID: T1303

- Name: Chronic Graft Versus Host Disease

- Relevance: LOW

- As Found: Unknown

- ID: T1482

- Name: Congenital Diaphragmatic Hernia

- Relevance: HIGH

- As Found: Diaphragmatic Hernia

### Condition Browse Module - Meshes

- ID: D000006976

- Term: Hypertension, Pulmonary

- ID: D000065630

- Term: Hernias, Diaphragmatic, Congenital

- ID: D000006547

- Term: Hernia

- ID: D000006548

- Term: Hernia, Diaphragmatic

### Intervention Browse Module - Ancestors

- ID: D000014665

- Term: Vasodilator Agents

- ID: D000058986

- Term: Phosphodiesterase 5 Inhibitors

- ID: D000010726

- Term: Phosphodiesterase Inhibitors

- ID: D000004791

- Term: Enzyme Inhibitors

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

- ID: D000064804

- Term: Urological Agents

### Intervention Browse Module - Browse Branches

- Abbrev: VaDiAg

- Name: Vasodilator Agents

- Abbrev: Urol

- Name: Urological Agents

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: Resp

- Name: Respiratory System Agents

- Abbrev: AnCoag

- Name: Anticoagulants

- Abbrev: Ot

- Name: Other Dietary Supplements

### Intervention Browse Module - Browse Leaves

- ID: M292

- Name: Sildenafil Citrate

- Relevance: HIGH

- As Found: Atrial Fibrillation

- ID: M12507

- Name: Nitric Oxide

- Relevance: LOW

- As Found: Unknown

- ID: M13629

- Name: Phosphodiesterase Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M21320

- Name: Citric Acid

- Relevance: LOW

- As Found: Unknown

- ID: M1837

- Name: Sodium Citrate

- Relevance: LOW

- As Found: Unknown

- ID: M17412

- Name: Vasodilator Agents

- Relevance: LOW

- As Found: Unknown

- ID: M29332

- Name: Phosphodiesterase 5 Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M7951

- Name: Enzyme Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: T382

- Name: Citrate

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000068677

- Term: Sildenafil Citrate

### Misc Info Module

- Version Holder: 2024-05-24

## Results Section

### Adverse Events Module

**Description:** Study was terminated. All efforts to locate the data have been exhausted and data has been lost and/or destroyed.

#### Event Groups

**Group ID:** EG000

**Title:** Sildenafil

**Description:** Sildenafil x 45 days

sildenafil: Sildenafil 0.5 mg/kg every 6 hours orally x 45 d

**ID:** EG000

**Title:** Sildenafil

**Group ID:** EG001

**Title:** Placebo

**Description:** Placebo x 45 d

Placebo: Placebo suspension (equal volume to experimental drug) x 45 days

**ID:** EG001

**Title:** Placebo

**Frequency Threshold:** 0

**Time Frame:** Study was terminated. All efforts to locate the data have been exhausted and data has been lost and/or destroyed.

## Results Section - Baseline Characteristics Module

### Denomination Counts

**Group ID:** BG000

**Value:** 0

**Group ID:** BG001

**Value:** 0

**Group ID:** BG002

**Value:** 0

**Units:** Participants

### Group

**ID:** BG000

**Title:** Sildenafil

**Description:** Sildenafil x 45 days

sildenafil: Sildenafil 0.5 mg/kg every 6 hours orally x 45 d

### Group

**ID:** BG001

**Title:** Placebo

**Description:** Placebo x 45 d

Placebo: Placebo suspension (equal volume to experimental drug) x 45 days

### Group

**ID:** BG002

**Title:** Total

**Description:** Total of all reporting groups

### Measure

**Category Title:** <=18 years

**Category Title:** Between 18 and 65 years

**Category Title:** >=65 years

**Class Title:** 

### Measure

**Category Title:** Female

**Category Title:** Male

**Class Title:** 

### Measure

**Class Title:** United States

**Denomination Units Selected:** 

## Results Section - Baseline Characteristics Module

### Measure 1
**Title:** Age, Categorical
### Measure 2
**Title:** Sex: Female, Male
### Measure 3
**Title:** Region of Enrollment
**Unit of Measure:** participants
**Population Description:** Study was terminated. All efforts to locate the data have been exhausted and data has been lost and/or destroyed.
## Results Section - More Information Module
### Certain Agreement
**PI Sponsor Employee:** True
### Point of Contact
**Email:** roberta.keller@ucsf.edu
**Organization:** University of California, San Francisco
**Phone:** (415) 476-1888
**Title:** Roberta Keller, MD
## Results Section - Outcome Measures Module
### Outcome Measure 1
### Outcome Measure 2
### Outcome Measure 3
### Outcome Measure 4
### Outcome Measure 5
### Outcome Measure 6
## Results Section
### Outcome Measures Module
#### Outcome Measure 1
#### Outcome Measure 2
#### Outcome Measure 3
#### Outcome Measure 4
#### Outcome Measure 5
#### Outcome Measure 6
## Results Section
### Outcome Measures Module
#### Outcome Measure 1
**Population Description:** Study was terminated. All efforts to locate the data have been exhausted and data has been lost and/or destroyed.
**Reporting Status:** POSTED
**Time Frame:** 7 weeks
**Title:** Estimated Systolic Pulmonary Arterial Pressure at Final Echocardiogram
**Type:** PRIMARY
##### Group
**Description:** Sildenafil x 45 days

sildenafil: Sildenafil 0.5 mg/kg every 6 hours orally x 45 d
**ID:** OG000
**Title:** Sildenafil
##### Group
**Description:** Placebo x 45 d

Placebo: Placebo suspension (equal volume to experimental drug) x 45 days
**ID:** OG001
**Title:** Placebo
#### Outcome Measure 2
**Population Description:** Study was terminated. All efforts to locate the data have been exhausted and data has been lost and/or destroyed.
**Reporting Status:** POSTED
**Time Frame:** 7 weeks
**Title:** Systemic Levels of Vasoactive Substances at the Time of Final Echocardiogram
**Type:** SECONDARY
##### Group
**Description:** Sildenafil x 45 days

sildenafil: Sildenafil 0.5 mg/kg every 6 hours orally x 45 d
**ID:** OG000
**Title:** Sildenafil
##### Group
**Description:** Placebo x 45 d

Placebo: Placebo suspension (equal volume to experimental drug) x 45 days
**ID:** OG001
**Title:** Placebo
#### Outcome Measure 3
**Population Description:** Study was terminated. All efforts to locate the data have been exhausted and data has been lost and/or destroyed.
**Reporting Status:** POSTED
**Time Frame:** 2 years
**Title:** Adverse Effects of Sildenafil Therapy
**Type:** SECONDARY
##### Group
**Description:** Sildenafil x 45 days

sildenafil: Sildenafil 0.5 mg/kg every 6 hours orally x 45 d
**ID:** OG000
**Title:** Sildenafil
##### Group
**Description:** Placebo x 45 d

Placebo: Placebo suspension (equal volume to experimental drug) x 45 days
**ID:** OG001
**Title:** Placebo
#### Outcome Measure 4
**Population Description:** Study was terminated. All efforts to locate the data have been exhausted and data has been lost and/or destroyed.
**Reporting Status:** POSTED
**Time Frame:** 2 years
**Title:** Somatic Growth at 1 and 2 Years of Age
**Type:** SECONDARY
##### Group
**Description:** Sildenafil x 45 days

sildenafil: Sildenafil 0.5 mg/kg every 6 hours orally x 45 d
**ID:** OG000
**Title:** Sildenafil
##### Group
**Description:** Placebo x 45 d

Placebo: Placebo suspension (equal volume to experimental drug) x 45 days
**ID:** OG001
**Title:** Placebo
#### Outcome Measure 5
**Population Description:** Study was terminated. All efforts to locate the data have been exhausted and data has been lost and/or destroyed.
**Reporting Status:** POSTED
**Time Frame:** 2 years
**Title:** Neurodevelopmental Outcome at 1 and 2 Years of Age
**Type:** SECONDARY
##### Group
**Description:** Sildenafil x 45 days

sildenafil: Sildenafil 0.5 mg/kg every 6 hours orally x 45 d
**ID:** OG000
**Title:** Sildenafil
##### Group
**Description:** Placebo x 45 d

Placebo: Placebo suspension (equal volume to experimental drug) x 45 days
**ID:** OG001
**Title:** Placebo
#### Outcome Measure 6
**Population Description:** Study was terminated. All efforts to locate the data have been exhausted and data has been lost and/or destroyed.
**Reporting Status:** POSTED
**Time Frame:** 2 years
**Title:** Respiratory Status at 1 and 2 Years of Age
**Type:** SECONDARY
##### Group
**Description:** Sildenafil x 45 days

sildenafil: Sildenafil 0.5 mg/kg every 6 hours orally x 45 d
**ID:** OG000
**Title:** Sildenafil
##### Group
**Description:** Placebo x 45 d

Placebo: Placebo suspension (equal volume to experimental drug) x 45 days
**ID:** OG001
**Title:** Placebo
### Participant Flow Module
#### Group
**Description:** Sildenafil x 45 days

sildenafil: Sildenafil 0.5 mg/kg every 6 hours orally x 45 d
**ID:** FG000
**Title:** Sildenafil
#### Group
**Description:** Placebo x 45 d

Placebo: Placebo suspension (equal volume to experimental drug) x 45 days
**ID:** FG001
**Title:** Placebo
#### Period
**Title:** Overall Study
##### Milestone
**Type:** STARTED
###### Achievement
**Group ID:** FG000
**Number of Subjects:** 0
###### Achievement
**Group ID:** FG001
**Number of Subjects:** 0
##### Milestone
**Type:** COMPLETED
###### Achievement
**Group ID:** FG000
**Number of Subjects:** 0
###### Achievement
**Group ID:** FG001
**Number of Subjects:** 0
##### Milestone
**Type:** NOT COMPLETED
###### Achievement
**Group ID:** FG000
**Number of Subjects:** 0
###### Achievement
**Group ID:** FG001
**Number of Subjects:** 0
**Recruitment Details:** Study was terminated. All efforts to locate the data have been exhausted and data has been lost and/or destroyed.
**Has Results:** True