Treatment of Deficient Subclass or Anti-polysaccharide Antibody Response (Subklasse)

Treatment in Patients With Recurrent Infections and IgG Subclass Deficiency, and/or Deficient Anti-Polysaccharide Antibody Response

There is no consensus on the treatment of patients with recurrent infections and isolated immunoglobulin G (IgG)-subclass deficiency and/or selective antipolysaccharide antibody deficiency. Therefore, the Dutch Inter University Working Party will start a study in which the treatment with antibiotics is compared with intravenous immunoglobulin therapy with respect to clinical outcome measures in both children and adults with this disorder.

Study Overview

• Status: Completed
• Conditions: Infections; IgG Deficiency
• Intervention / Treatment: Drug: intravenous immunoglobulins; Drug: antibiotics

Detailed Description

There is no consensus on the treatment of patients with recurrent infections and isolated IgG-subclass deficiency and/or selective antipolysaccharide antibody deficiency. At present, there are no robust criteria to predict which patient will or will not respond adequately to antibiotic treatment or to IVIG. Furthermore, it is unknown whether IVIG treatment improves the quality of life in these patients. Therefore, the Dutch InterUniversity Working Party intends to start a study in this patient group. In this study, treatment for a year with antibiotics will be compared with a year intravenous immunoglobulin therapy with respect to clinical outcome measures in both children and adults with this disorder.

The patient will visit the clinic every 3 months during which laboratory tests and physiological measurements will be performed. Moreover the occurrence of infections and fever, the use of antibiotics, hospital admissions, and quality of life will be documented.

The study should result in a national harmonization in the treatment of this patient group. To this end, the results of the study will be used to compile a treatment protocol for this group of patients in the Netherlands and if applicable also in other countries worldwide.

• Study Type: Interventional
• Enrollment (Actual): 55
• Phase: Phase 4

Contacts and Locations

Study Locations

• Netherlands
  • Amsterdam, Netherlands
    • AMC
  • Amsterdam, Netherlands
    • VU
  • Den Bosch, Netherlands
    • Jeroen Bosch Ziekenhuis
  • Groningen, Netherlands
    • UMCG
  • Leiden, Netherlands
    • LUMC
  • Maastricht, Netherlands
    • azM
  • Nijmegen, Netherlands
    • UMC St Radboud
  • Rotterdam, Netherlands
    • Erasmus MC
  • Utrecht, Netherlands
    • UMCU

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• IgG subclass deficiency and/or (selective) antipolysaccharide antibody deficiency
• At least 2 physician documented infections before the start of the current treatment or in the last 6 months for newly diagnosed patients.
• Total serum IgG > 4 g/l
• ≥ 5 years of age
• Informed consent

Exclusion Criteria:

• Treatment with any other investigational drug within 7 days prior to study entry, or previous enrolment in this study
• Allergic reactions against human plasma/plasma products, or co-trimoxazole
• An ongoing progressive terminal disease
• Pregnancy or lactation
• History of (transient) cerebrovascular accident or coronary insufficiency
• Renal insufficiency (plasma creatinin > 115 µmol/L; or creatinin clearance <20 ml/min)
• An ongoing active disease causing general symptoms e.g. chronic active hepatitis or persistent enterovirus infection with ongoing systemic complaints
• Detectable anti-IgA antibodies
• Active systemic lupus erythematosus (SLE)
• Glucose-6-phosphate hydrogenase deficiency

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: Antibiotics; A: co-trimoxazole prophylactically for 12 months followed by intravenous immunoglobulin treatment for 12 months. Treatments will be separated by a washout period of 3 months during which co-trimoxazole will be given.	Drug: intravenous immunoglobulins; Adults: 600 mg/kg bodyweight every 3 weeks; Children: 800 mg/kg bodyweight every 3 week; Other Names: Nanogam; Drug: antibiotics; Children ≥5-12: If well tolerated, 4 mg trimethoprim and 20 mg sulfamethoxazole per kg bodyweight once daily, every day of the week (max160/800mg/day), combined with 5 mg folic acid.; Adults and children ≥12 years or ≥40 kg: If well tolerated, 160 mg trimethoprim and 800 mg sulfamethoxazole once daily, every day of the week combined with 5 mg folic acid.; Other Names: co-trimoxazol; if not lorated: azitromycine
OTHER: intravenous immunoglobulins; B: intravenous immunoglobulin treatment for 12 months followed by co-trimoxazole prophylactically for 12 months. Treatments will be separated by a washout period of 3 months during which co-trimoxazole will be given.	Drug: intravenous immunoglobulins; Adults: 600 mg/kg bodyweight every 3 weeks; Children: 800 mg/kg bodyweight every 3 week; Other Names: Nanogam; Drug: antibiotics; Children ≥5-12: If well tolerated, 4 mg trimethoprim and 20 mg sulfamethoxazole per kg bodyweight once daily, every day of the week (max160/800mg/day), combined with 5 mg folic acid.; Adults and children ≥12 years or ≥40 kg: If well tolerated, 160 mg trimethoprim and 800 mg sulfamethoxazole once daily, every day of the week combined with 5 mg folic acid.; Other Names: co-trimoxazol; if not lorated: azitromycine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
the number, duration and type of infection (including use of antibiotics to treat infections), days of fever, hospital admissions and, if applicable, days absent from school or work due to infections.	27 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Safety will be monitored by occurrence of adverse events, vital signs, and laboratory measurements.	27 months

Collaborators and Investigators

• Sponsor: Prothya Biosolutions
• Investigators: Principal Investigator: J T van Dissel, PhD, MD, LUMC; Principal Investigator: T W Kuijpers, PhD, MD, AIDS Malignancy Consortium; Principal Investigator: E AM Sanders, PhD, MD, UMCU

Study record dates

Study Major Dates

• Study Start: November 1, 2007
• Primary Completion (ACTUAL): July 1, 2014
• Study Completion (ACTUAL): July 1, 2014

Study Registration Dates

• First Submitted: August 29, 2007
• First Submitted That Met QC Criteria: August 29, 2007
• First Posted (ESTIMATE): August 30, 2007

Study Record Updates

• Last Update Posted (ESTIMATE): April 6, 2015
• Last Update Submitted That Met QC Criteria: April 3, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: Immunoglobulins, Intravenous; therapy; co-trimoxazole; IgG subclass deficiency; Anti-polysaccharide deficiency
• Additional Relevant MeSH Terms: Immunologic Deficiency Syndromes; Immune System Diseases; Hematologic Diseases; Blood Protein Disorders; Dysgammaglobulinemia; Infections; IgG Deficiency; Physiological Effects of Drugs; Anti-Infective Agents; Immunologic Factors; Antibodies; Immunoglobulins; Immunoglobulins, Intravenous; Anti-Bacterial Agents; gamma-Globulins; Rho(D) Immune Globulin
• Other Study ID Numbers: IUWP2005.01