Official Title: “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 Type: Interventional

Study Design: Prevention, Randomized, Open Label, Uncontrolled, Crossover Assignment, Safety/Efficacy Study

Study Primary Completion Date: May 2011

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.

Intervention(s) in this Clinical Trial

• Drug: intravenous immunoglobulins
  • Adults: 600 mg/kg bodyweight every 3 weeks Children: 800 mg/kg bodyweight every 3 week
• Drug: co-trimoxazole
  • 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.

Arms, Groups and Cohorts in this Clinical Trial

• Other: A
  • 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.
• Other: B
  • 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.

Primary Measures

• 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.
  • Time Frame: 27 months
    Safety Issue?: No

Secondary Measures

• Safety will be monitored by occurrence of adverse events, vital signs, and laboratory measurements.
  • Time Frame: 27 months
    Safety Issue?: Yes

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 5 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Sanquin

Overall Clinical Trial Officials and Contacts

J T van Dissel, PhD, MD Principal Investigator LUMC  

Overall Contact: P S Strengers, MD  p.strengers@sanquin.nl

Information obtained from ClinicalTrials.gov on October 10, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00522821

Study ID Number: IUWP2005.01

ClinicalTrials.gov Identifier: NCT00522821

Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)