Efficacy of Oral Supplementation With Magnesium to Reduce Febrile Neutropenia

Febrile Neutropenia Clinical Trial

Official title:

Efficacy of Oral Supplementation With Magnesium to Reduce Febrile Neutropenia in Pediatric Oncology Patients Treated With Cisplatin-Based Chemotherapy: Randomized Clinical Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03449693
• Other study ID #: HIM-2017-085
• Status: Recruiting
• Phase: Phase 2
• First received: February 21, 2018
• Last updated: March 1, 2018
• Start date: October 19, 2017
• Est. completion date: December 2019

Study information

• Verified date: March 2018
• Source: Universidad Nacional Autonoma de Mexico
• Contact: Victoria E Barrios, QFB
• Phone: +52 1 2291290208
• Email: victoria.barrios[@]cinvestav.mx
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Clinical Trial. Open label. Parallel Groups. The purpose of the study is to determine the efficacy of oral supplementation with magnesium oxide to reduce febrile neutropenia episodes in pediatric oncology patients treated with cisplatin-based chemotherapy.

Description:

Febrile neutropenia (FN) is a worrying outcome in children receiving chemotherapy because it increments the risk of major complications, reduces quality of life and increments treatment costs. Moreover, it is the most common diagnosis in pediatric oncology patients that enter emergency rooms and the second most important cause of hospitalization, just behind hospitalization for administration of chemotherapy.

In Mexico, incidence of FN is of 62% of children with solid tumors treated with cisplatin-based chemotherapy (CBC). Cisplatin is one of the most nephrotoxic drugs being used in clinical settlements. The assessment of nephrotoxicity is made with the manifestation of tubular damage that causes electrolyte losses, specially of magnesium. Recently, our investigation group reported that there is an association of hypomagnesemia and the apparition of FN. This association has a biologic explanation in the fact that magnesium is a necessary cofactor for the neutrophil's diapedesis and the activation of complement cascade. To our knowledge, the role of magnesium supplementation has not been explored. With this evidence in mind, the investigators wondered if oral supplementation with magnesium will reduce FN episodes in pediatric oncology patients treated with CBC.

Objective: Determine the efficacy of oral supplementation with magnesium to reduce FN episodes in pediatric oncology patients treated with CBC.

Hypothesis: Previous clinical trials made in adult population have reported that supplementation with magnesium salts reduce episodes of hypomagnesemia in between 13 and 50%. Thus, oral supplementation with magnesium oxide will reduce 20% of FN episodes in pediatric oncology patients treated with CBC.

Materials and Methods: Randomized Clinical Trial, open-label, parallel groups of children over the age of nine with solid tumors treated with CBC at the Haemato-Oncology Department of the Hospital Infantil de México. To prove the hypothesis, it is required to randomize 107 CBC cycles to the intervention group and 107 CBC cycles to the control group. The sample size calculation was made by using the two proportions formula. Randomize of children will be made when they receive CBC indication. Patients assigned to the intervention group will receive institutional attention protocol plus a bottle of magnesium oxide, at the moment of hospitalization discharge. Patients assigned to the control group will receive only institutional attention protocol. The follow-up of patients will be made until an episode of FN appears or until the patient comes back for another CBC cycle. FN assessment will be measured with a unique temperature >38.3°C or a sustained temperature >38°C over the course of an hour plus a count of neutrophils under 1000 cells/mm3. The efficacy of oral supplementation with magnesium oxide will be determined by a Relative Risks calculation with confidence interval of 95% (CI95%). Moreover, Absolute Risk Reduction will be calculated, as well as Necessary Number to Treat. To adjust the principal variable a multivariate analysis will be made with a multiple logistic regression. The analysis will be made by protocol and by intention to treat.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 214
• Est. completion date: December 2019
• Est. primary completion date: December 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 9 Years to 18 Years

Eligibility

Inclusion Criteria:

• Pediatric patients > 9 years old

• Pediatric patients with solid tumors treated with cisplatin-based chemotherapy

• Signing of Informed Consent from the parents

• Signing of Informed Assent from the children

Non-inclusion Criteria:

• Patients whose parents do not sign the Informed Consent

• Patients with magnesium losing tubulopathy

• Patients with hypomagnesemia previous to the cisplatin-based chemotherapy

Exclusion Criteria:

• Patients whose parents retire the Informed Consent

Related Conditions & MeSH terms

• Febrile Neutropenia
• Fever
• Neutropenia

Intervention

Dietary Supplement:
• Magnesium Oxide Supplement
Magnesium Oxide tablet

Locations

Country	Name	City	State
Mexico	Hospital Infantil de Mexico Dr. Federico Gomez	Cuauhtémoc	Ciudad De México

Sponsors (3)

Lead Sponsor	Collaborator
Universidad Nacional Autonoma de Mexico	Centro de Investigación y Estudios Avanzados del Instituto Politécnico Nacional, Hospital Infantil de Mexico Federico Gomez

Country where clinical trial is conducted

Mexico, 

References & Publications (10)

Castagnola E, Paola D, Giacchino R, Rossi R, Viscoli C. Economic aspects of empiric antibiotic therapy for febrile neutropenia in children with cancer. Support Care Cancer. 1998 Nov;6(6):524-8. — View Citation

Castelán-Martínez OD, Rodríguez-Islas F, Vargas-Neri JL, Palomo-Colli MA, López-Aguilar E, Clark P, Castañeda-Hernández G, Rivas-Ruiz R. Risk Factors for Febrile Neutropenia in Children With Solid Tumors Treated With Cisplatin-based Chemotherapy. J Pediatr Hematol Oncol. 2016 Apr;38(3):191-6. doi: 10.1097/MPH.0000000000000515. — View Citation

Freifeld AG, Pizzo PA. The outpatient management of febrile neutropenia in cancer patients. Oncology (Williston Park). 1996 Apr;10(4):599-606, 611-2; discussion 615-6. Review. — View Citation

Klaassen RJ, Goodman TR, Pham B, Doyle JJ. "Low-risk" prediction rule for pediatric oncology patients presenting with fever and neutropenia. J Clin Oncol. 2000 Mar;18(5):1012-9. — View Citation

Knijnenburg SL, Mulder RL, Schouten-Van Meeteren AY, Bökenkamp A, Blufpand H, van Dulmen-den Broeder E, Veening MA, Kremer LC, Jaspers MW. Early and late renal adverse effects after potentially nephrotoxic treatment for childhood cancer. Cochrane Database Syst Rev. 2013 Oct 8;(10):CD008944. doi: 10.1002/14651858.CD008944.pub2. Review. — View Citation

Lajer H, Daugaard G. Cisplatin and hypomagnesemia. Cancer Treat Rev. 1999 Feb;25(1):47-58. Review. — View Citation

Martin M, Diaz-Rubio E, Casado A, López Vega JM, Sastre J, Almenarez J. Intravenous and oral magnesium supplementations in the prophylaxis of cisplatin-induced hypomagnesemia. Results of a controlled trial. Am J Clin Oncol. 1992 Aug;15(4):348-51. — View Citation

Mueller EL, Sabbatini A, Gebremariam A, Mody R, Sung L, Macy ML. Why pediatric patients with cancer visit the emergency department: United States, 2006-2010. Pediatr Blood Cancer. 2015 Mar;62(3):490-5. doi: 10.1002/pbc.25288. Epub 2014 Oct 24. Erratum in: Pediatr Blood Cancer. 2018 Apr;65(4):. — View Citation

Willox JC, McAllister EJ, Sangster G, Kaye SB. Effects of magnesium supplementation in testicular cancer patients receiving cis-platin: a randomised trial. Br J Cancer. 1986 Jul;54(1):19-23. — View Citation

Zarif Yeganeh M, Vakili M, Shahriari-Ahmadi A, Nojomi M. Effect of Oral Magnesium Oxide Supplementation on Cisplatin-Induced Hypomagnesemia in Cancer Patients: A Randomized Controlled Trial. Iran J Public Health. 2016 Jan;45(1):54-62. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Febrile Neutropenia	Unique temperature >38.3°C or sustained temperature >38°C over the course of an hour, and a total count of neutrophils <1000 cells/mm3.	After randomization until day 30
Secondary	Time passed from cisplatin-based chemotherapy until the apparition of febrile neutropenia	Total of days passed from the randomization up to the apparition of febrile neutropenia	After randomization until day 30
Secondary	Safety of Oral Supplementation with Magnesium	Evaluate the apparition of adverse effects of oral supplement of magnesium oxide	Evaluate the apparition of adverse effects of oral supplement of magnesium oxide Time Frame: After randomization until day 30
Secondary	Hypomagnesemia	Serum magnesium <1.6 mg/mL	After randomization until day 30