Impact of Valganciclovir on Severe IRIS-Kaposi Sarcoma Mortality: an Open-label, Parallel, Randomized Controlled-trial.

NCT03296553 | Completed Phase 2 Results DMC

• 1 other identifier: (015/031/INI) (CEI/950/15)
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Kaposi sarcoma (KS) has an unpredictable course, patients with disseminated KS starting combined Antiretroviral Therapy can develop Immune Reconstitution Syndrome (IRIS), with a severe clinical presentation and high mortality (severe-IRIS-KS). The objective of this study is to evaluate the presence of Severe IRIS-KS and it´s attributable mortality in patients with AIDS and disseminated KS with the use of valganciclovir prior to the initiation of cART compared with the standard management of immediate cART initiation.

Conditions

Kaposi Sarcoma; Human Immunodeficiency Virus; Immune Reconstitution Syndrome

Outcome Measures

Primary Outcomes (1)

• Number of Participants Who Died of Immune Reconstitution Inflammatory Syndrome Associated to Kaposi Sarcoma (IRIS-KS)

  We measured the number of patients who died of IRIS-KS following the definition of IRIS-KS that is specified in the protocol.

  48 weeks

Study Arms (2)

Valganciclovir

EXPERIMENTAL

Oral Valgancyclovir 900 mg twice in a day during 4 weeks prior to initiation of cART (combined antirretroviral therapy) until suppression of HHV-8.

Drug: Valganciclovir

Antiretroviral combinations

ACTIVE COMPARATOR

Standard treatment with cART according to current HIV Therapy Mexican guidelines.

Drug: Antiretroviral Combinations

Interventions

Valganciclovir DRUG

The experimental group will receive Valganciclovir 900 mg twice in a day before the initiation of cART until viral load of HHV-8 is undetectable.

Also known as: Valcyte

Valganciclovir

Antiretroviral Combinations DRUG

Patients will receive standard antiretroviral treatment as recommended

Also known as: cART

Antiretroviral combinations

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients will be included with AIDS naïve to antiretroviral therapy and severe KS, who accept to participate and who sign the letter of informed consent.
• The following are the KS severity criteria: pulmonary compromise, and/or digestive tract compromise, and/or disseminated cutaneous, and/or lymphadenopathic compromise with generalized lymphedema.

You may not qualify if:

• Patients with another synchronic malignant neoplasm
• Patients receiving corticosteroids
• Patients with active hepatitis B and/or hepatitis C
• Patients with KS limited to skin with less than 30 lesions.
• Patients with APACHE II score ≥15 points.

Sponsors & Collaborators

• National Institute of Cancerología: lead
• Instituto Nacional de Enfermedades Respiratorias: collaborator

Study Sites (1)

Instituto Nacional de Cancerologia

Mexico City, 14080, Mexico

Location

Related Publications (6)

• Gottlieb GJ, Ragaz A, Vogel JV, Friedman-Kien A, Rywlin AM, Weiner EA, Ackerman AB. A preliminary communication on extensively disseminated Kaposi's sarcoma in young homosexual men. Am J Dermatopathol. 1981 Summer;3(2):111-4. doi: 10.1097/00000372-198100320-00002. No abstract available.

  PMID: 7270808 BACKGROUND

• Hymes KB, Cheung T, Greene JB, Prose NS, Marcus A, Ballard H, William DC, Laubenstein LJ. Kaposi's sarcoma in homosexual men-a report of eight cases. Lancet. 1981 Sep 19;2(8247):598-600. doi: 10.1016/s0140-6736(81)92740-9.

  PMID: 6116083 BACKGROUND

• Safai B, Johnson KG, Myskowski PL, Koziner B, Yang SY, Cunningham-Rundles S, Godbold JH, Dupont B. The natural history of Kaposi's sarcoma in the acquired immunodeficiency syndrome. Ann Intern Med. 1985 Nov;103(5):744-50. doi: 10.7326/0003-4819-103-5-744.

  PMID: 3901851 BACKGROUND

• Yarchoan R, Uldrick TS. HIV-Associated Cancers and Related Diseases. N Engl J Med. 2018 Mar 15;378(11):1029-1041. doi: 10.1056/NEJMra1615896.

  PMID: 29539283 BACKGROUND

• Lacombe JM, Boue F, Grabar S, Viget N, Gazaignes S, Lascaux-Cametz AS, Pacanowski J, Partisani M, Launay O, Matheron S, Rosenthal E, Rouveix E, Tattevin P, de Truchis P, Costagliola D, Goedert JJ. Risk of Kaposi sarcoma during the first months on combination antiretroviral therapy. AIDS. 2013 Feb 20;27(4):635-43. doi: 10.1097/QAD.0b013e32835cba6c.

  PMID: 23196937 BACKGROUND

• Cornejo-Juarez P, Islas-Munoz B, Ramirez-Ibarguen AF, Rosales-Pedraza G, Chavez-Mazari B, Martinez-Orozco A, Volkow-Fernandez P. Bone Marrow Culture Yield for the Diagnosis of Opportunistic Diseases in Patients with AIDS and Disseminated Kaposi Sarcoma. Curr HIV Res. 2020;18(4):277-282. doi: 10.2174/1570162X18666200603145640.

  PMID: 32493198 DERIVED

MeSH Terms

Conditions

Sarcoma, Kaposi; Acquired Immunodeficiency Syndrome; Immune Reconstitution Inflammatory Syndrome

Interventions

Valganciclovir

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Sarcoma; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Vascular Tissue; HIV Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Ganciclovir; Acyclovir; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

We acknowledge some limitations in our study. First, the sample size was small. And second in estimating the sample size for the trial we overestimated the expected impact of valganciclovir treatment on mortality.

Results Point of Contact

• Title: Dr. Patricia Volkow
• Organization: Instituto Nacional de Cancerología

pvolkowf@gmail.com

01 55 5628 0400

Study Officials

• Patricia Amalia Volkow Fernández, MD

  Instituto Nacional de Cancerologia, Columbia

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Infectious disease consultant, Clinical Professor

Study Record Dates

• First Submitted: September 20, 2017
• First Posted: September 28, 2017
• Study Start: October 1, 2015
• Primary Completion: August 26, 2019
• Study Completion: August 26, 2019
• Last Updated: January 27, 2022
• Results First Posted: January 27, 2022

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

ME (1)