Diseases and Abnormalities at or Before Birth

All Conditions

Neoplasms

Blood and Lymph Conditions

Rare Diseases

Congenital Abnormalities

Lymphangioma

Lymphatic Abnormalities

Lymphatic Diseases

Neoplasms by Histologic Type

Lymphatic Malformations

Vasodilator Agents

Urological Agents

All Drugs and Chemicals

Anticoagulants

Other Dietary Supplements

Sildenafil Citrate

Citric Acid

Sodium Citrate

Phosphodiesterase 5 Inhibitors

Phosphodiesterase Inhibitors

Enzyme Inhibitors

Citrate

Placebo Drug: Placebo tablets (resembling Revatio)

Active Drug: Sildenafil tablets (Revatio)

Sildenafil 20 mg tablets

Placebo tablets (resembling Revatio)

Joyce Teng, MD, PhD

A Phase 2 study to evaluate safety and efficacy of sildenafil taken orally to improve or resolve lymphatic malformations in children. Subjects may receive either placebo or treatment in an oral dosage with an open label extension for subjects who received placebo. The study treatment assignment will be randomized in a double blind fashion. MRI examination will evaluate change in lesion volume due to treatment. Other safety and efficacy measures will be taken through the 32-week study duration.

Funding Source - FDA OOPD

Lymphatic malformations (LMs) are localized areas of abnormal development of the lymphatic system that commonly occur in the head and neck of children. LMs are considered a rare or orphan disease which causes complications including pain, ulceration, secondary infection, infiltration of other organs, and death. Current therapies involve surgical excision or methods of chemical or physical destruction of portions of lesions. No therapies are uniformly effective and all have the risk of significant adverse events. We recently witnessed almost complete resolution of a LM lesion in a child who was treated with sildenafil oral therapy for pulmonary arterial hypertension. We have subsequently evaluated additional subjects who improved with sildenafil. The goal of this clinical research trial is to document the benefit or absence of benefit of sildenafil therapy for LMs and identify which type of patient will benefit from sildenafil. This study is a double-blind placebo-controlled trial which involves precise documentation of volume changes associated with therapy or placebo by using MRI segmentation techniques. We will also observe and document the clinical response to sildenafil or placebo using clinical evaluation scores and surveys. The results of the study should identify characteristics of LM lesions which may suggest a beneficial response to sildenafil therapy. Sildenafil has very low risk of side effects in the dosage used in this trial. Documentation of an effective response of LMs to sildenafil will accelerate the interest in, and the ability to understand, the mechanisms of LM formation and treatment.

Sildenafil for the Treatment of Lymphatic Malformations

Phase 2 Study of Sildenafil for the Treatment of Lymphatic Malformations

The IPD will only be shared de-identified to our study staff and human subjects approved subsites. These results will eventually be published, but will be completed around 2022.

Participants will be followed for the duration of the study, an expected average of 20 weeks.

Subject's evaluation of the overall change in lymphatic malformation. Participants will be followed from baseline to 20 weeks.

Patients rated change as no improvement, minimal improvement (1-25% change), fair improvement (25-50% change), good improvement (50-75% change), and excellent improvement (75-100% change).

Ann & Robert H Lurie Children's Hospital of Chicago

Stanford University

Placebo (resembling Revatio) for 20 weeks.

Double-Blind Placebo

Participants who complete placebo then receive active sildenafil (Revatio) for 20 weeks three times daily (weight-based: 10 mg TID for participants weighing 8-20 kg; 20 mg TID for participants weighing \>20 kg).

Open-Label Sildenafil

Sildenafil (Revatio) for 20 weeks three times daily (weight-based: 10 mg TID for participants weighing 8-20 kg; 20 mg TID for participants weighing \>20 kg).

Double-Blind Sildenafil

Placebo (resembling Revatio) for 20 weeks. Participants randomized to placebo had the option to enter a 20-week open-label phase to receive active sildenafil (Revatio) for 20 weeks three times daily (weight-based: 10 mg TID for participants weighing 8-20 kg; 20 mg TID for participants weighing \>20 kg), followed by a 12 week follow-up period.

Double-Blind Placebo Then Open-Label Sildenafil

Sildenafil (Revatio) for 20 weeks three times daily (weight-based: 10 mg TID for participants weighing 8-20 kg; 20 mg TID for participants weighing \>20 kg), followed by a 12-week follow-up period.

Total

Age, Categorical

Sex: Female, Male

Ethnicity data are available for only 6 participants in the placebo group.

Ethnicity (NIH/OMB)

African American

Asian

Indian

White

More than one race

Unknown/Not reported

Race data are available for only 6 participants in the placebo group.

Race/Ethnicity, Customized

United States

Region of Enrollment

Baseline lesion volume data are available for only 6 participants in the placebo group.

Lesion volume

Only 1 of 4 planned sites participated in this trial; the study did not meet its planned enrollment and the results are underpowered.

Jean Teng, MD, PhD

Placebo (resembling Revatio) for 20 weeks, followed by a 12 week follow-up period.

Participants who complete placebo then receive active sildenafil (Revatio) for 20 weeks three times daily (weight-based: 10 mg TID for participants weighing 8-20 kg; 20 mg TID for participants weighing \>20 kg), followed by a 12 week follow-up period.

Double-blind Sildenafil

Participants who completed each treatment period are included in the analysis

Change in Lesion Volume of the Test Medication as Evaluated by MRI Examination.

No improvement

Minimal improvement

Fair improvement

Good improvement

Excellent improvement

Participants with data at both baseline and week 20 are included in the analysis

Spots Global Cancer Trial Database for placebo tablets (resembling revatio)