Efficacy of Oral Supplementation With Magnesium to Reduce Febrile Neutropenia

NCT ID: NCT03449693

Last Updated: 2018-03-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

214 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-10-19

Study Completion Date

2019-12-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Febrile Neutropenia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Two groups: Intervention group and control group. The intervention group will receive institutional care protocol plus oral supplementation with magnesium. The control group will receive institutional care protocol only.
Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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Magnesium Oxide Supplement

Magnesium Oxide 250 mg tablet, daily for 30 days.

Group Type EXPERIMENTAL

Magnesium Oxide Supplement

Intervention Type DIETARY_SUPPLEMENT

Magnesium Oxide tablet

No Supplement

No Intervention

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Magnesium Oxide Supplement

Magnesium Oxide tablet

Intervention Type DIETARY_SUPPLEMENT

Other Intervention Names

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M250

Eligibility Criteria

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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


* 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
Minimum Eligible Age

9 Years

Maximum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hospital Infantil de Mexico Federico Gomez

OTHER

Sponsor Role collaborator

Centro de Investigación y Estudios Avanzados del Instituto Politécnico Nacional

UNKNOWN

Sponsor Role collaborator

Universidad Nacional Autonoma de Mexico

OTHER

Sponsor Role lead

Responsible Party

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Osvaldo Daniel Castelan Martinez

Full Time Associate Professor C

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Osvaldo D Castelán, PhD

Role: PRINCIPAL_INVESTIGATOR

Universidad Nacional Autónoma de México. Facultad de Estudios Superiores Zaragoza

Miguel A Palomo, PhD

Role: PRINCIPAL_INVESTIGATOR

Hospital Infantil de México Dr. Federico Gómez

Locations

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Hospital Infantil de Mexico Dr. Federico Gomez

Cuauhtémoc, Mexico City, Mexico

Site Status RECRUITING

Countries

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Mexico

Central Contacts

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Victoria E Barrios, QFB

Role: CONTACT

+52 1 2291290208

Facility Contacts

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Victoria E Barrios, QFB

Role: primary

+52 1 2291290208

Miguel A Palomo, MD

Role: backup

References

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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.

Reference Type BACKGROUND
PMID: 8723296 (View on PubMed)

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. doi: 10.1007/s005200050208.

Reference Type BACKGROUND
PMID: 9833301 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25345994 (View on PubMed)

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. doi: 10.1200/JCO.2000.18.5.1012.

Reference Type BACKGROUND
PMID: 10694551 (View on PubMed)

Castelan-Martinez OD, Rodriguez-Islas F, Vargas-Neri JL, Palomo-Colli MA, Lopez-Aguilar E, Clark P, Castaneda-Hernandez 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.

Reference Type BACKGROUND
PMID: 26907640 (View on PubMed)

Lajer H, Daugaard G. Cisplatin and hypomagnesemia. Cancer Treat Rev. 1999 Feb;25(1):47-58. doi: 10.1053/ctrv.1999.0097.

Reference Type BACKGROUND
PMID: 10212589 (View on PubMed)

Knijnenburg SL, Mulder RL, Schouten-Van Meeteren AY, Bokenkamp 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.

Reference Type BACKGROUND
PMID: 24101439 (View on PubMed)

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. doi: 10.1038/bjc.1986.147.

Reference Type BACKGROUND
PMID: 3524645 (View on PubMed)

Martin M, Diaz-Rubio E, Casado A, Lopez 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. doi: 10.1097/00000421-199208000-00016.

Reference Type BACKGROUND
PMID: 1514533 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27057522 (View on PubMed)

Castelan-Martinez OD, Palomo-Colli MA, Barrios-Lopez VE, Silva-Jivaja KM, Juarez-Villegas LE, Castaneda-Hernandez G, Sanchez-Rodriguez MA. Efficacy and safety of oral magnesium supplementation in reducing febrile neutropenia episodes in children with solid tumors treated with cisplatin-based chemotherapy: randomized clinical trial. Cancer Chemother Pharmacol. 2020 Nov;86(5):673-679. doi: 10.1007/s00280-020-04155-4. Epub 2020 Oct 8.

Reference Type DERIVED
PMID: 33030582 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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HIM-2017-085

Identifier Type: -

Identifier Source: org_study_id

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