Mortality Reduction After Oral Azithromycin: Morbidity Study (MORDORMorb)
2021年3月15日 更新者：University of California, San Francisco
Evaluating Impact of Azithromycin Mass Drug Administrations on All-cause Mortality and Antibiotic Resistance: Morbidity Study
The long-term goal of this study is to more precisely define the role of mass azithromycin treatments as an intervention for reducing childhood morbidity and increasing growth, and for the potential selection of antibiotic resistance.
The investigators propose a set of 3 cluster-randomized trials in Malawi, Niger, and Tanzania comparing communities randomized to oral azithromycin with those randomized to placebo.
To assess the generalizability of the intervention, investigators will monitor for antibiotic resistance, which could potentially limit adoption of mass antibiotic treatments.
The investigators will also assess several measures of infectious diseases.
The investigators hypothesize that mass azithromycin treatments will reduce childhood morbidity and will be accompanied by an acceptable level of antibiotic resistance.
調査の概要
詳細な説明
The investigators will assess childhood infectious disease morbidity and macrolide resistance over two years, comparing communities where children aged 1-60 months receive biannual oral azithromycin to communities where the children receive biannual oral placebo.
Randomization of Treatment Allocation. In each site, 30 communities within a contiguous area of 300,000 to 600,000 individuals will be randomized into the azithromycin or placebo arm. The investigators will use a simple random sample separately for each study site, but without stratification or block randomization within the site. These communities are being randomized from the same pool of communities eligible for a sister trial (Mortality Reduction After Oral Azithromycin (MORDOR) - Morbidity Study).
Specific Aims
Specific Aim 1: To assess whether macrolide resistance is greater in a population-based community sample of pre-school children, or in a clinic-based sample of ill pre-school children
Specific Aim 2: To assess whether biannual mass azithromycin treatments of pre-school children can eliminate ocular chlamydia in a hypoendemic area
Specific Aim 3: To assess the diversity of the microbiome of the nasopharynx, nares, conjunctiva, and gastrointestinal tract
研究の種類
介入
入学 (実際)
72000
段階
- フェーズ 4
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究場所
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California
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San Francisco、California、アメリカ、94143-0944
- UCSF Proctor Foundation
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Maryland
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Baltimore、Maryland、アメリカ、21205
- Johns Hopkins University
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London、イギリス
- London School of Hygiene & Tropical Medicine
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Kongwa、タンザニア
- Kongwa Trachoma Project
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Niamey、ニジェール
- The Carter Center, Niger
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Blantyre、マラウイ
- College of Medicine at the University of Malawi, Blantyre
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参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
1ヶ月歳以上 (子、大人、高齢者)
健康ボランティアの受け入れ
はい
受講資格のある性別
全て
説明
Inclusion Criteria:
Communities:
- The community location in target district.
- The community leader consents to participation in the trial
- The community's estimated population is between 200-2,000 people.
- The community is not in an urban area.
Individuals (Intervention):
- Children-treated arms (all 3 sites): All children aged 1-60 months (up to but not including the 5th birthday), as assessed at the most recent biannual census
Individuals (Examination & Sample Collection):
- All swabs, blood tests, and stool samples: A random sample of children aged 1-60 months (up to but not including the 5th birthday) based on the previous census
- Anthropometric measurements: All children aged 1-60 months (up to but not including the 5th birthday) will have anthropometric measurements assessed.
- Nasopharyngeal swabs in untreated children: A random sample of individuals aged 7 - 12 years (7th birthday up to but not including the 12th birthday), as assessed from the previous census
- Clinic-based nasopharyngeal swabs: All children aged 1-60 months (up to but not including the 5th birthday) who present to a local health clinic in the study area and report symptoms of a respiratory infection
Exclusion Criteria:
Individuals:
- Pregnant women
- All those who are allergic to macrolides or azalides
- Refusal of village chief (for village inclusion), or refusal of parent or guardian (for individual inclusion)
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：4倍
武器と介入
参加者グループ / アーム |
介入・治療 |
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アクティブコンパレータ：Biannual mass oral azithromycin
Comparison of childhood infectious and nutritional morbidity in communities randomized to azithromycin versus communities randomized to placebo. Children aged 1 month to 60 months per community will be offered weight or height-based, directly observed, oral azithromycin suspension every 6 months for 2 years Morbidity monitoring: Collect swabs (nasopharyngeal, nasal, conjunctival), blood samples, (thick/thin blood smears, hemoglobin, dried blood spots), and stool samples from 40 randomly selected children aged 1 month to 60 months per community; collect swabs (nasopharyngeal) from 40 randomly selected children aged 7-12 years per community. Anthropometry for all children aged 1 to 60 months per community. Collect nasopharyngeal swabs from all children aged 1-60 months who are seen at a local health clinic and have a respiratory complaint. |
Biannual mass oral azithromycin to children
他の名前：
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プラセボコンパレーター：Biannual mass oral placebo
Comparison of childhood infectious and nutritional morbidity in communities randomized to azithromycin versus communities randomized to placebo. Children aged 1 month to 60 months per community will be offered weight or height-based, directly observed, oral placebo every 6 months for 2 years Collect swabs (nasopharyngeal, nasal, conjunctival), blood samples, (thick/thin blood smears, hemoglobin, dried blood spots), and stool samples from 40 randomly selected children aged 1 month to 60 months per community; collect swabs (nasopharyngeal) from 40 randomly selected children aged 7-12 years per community Anthropometry for all children aged 1 to 60 months per community Collect nasopharyngeal swabs from all children aged 1-60 months who are seen at a local health clinic and have a respiratory complaint |
Biannual mass oral placebo to children
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
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Presence of malaria parasites on thick blood smear or Rapid Diagnostic Test (RDT) in children 1-60 months
時間枠：Each site will report outcomes at 24 months; Niger will also report outcomes at 48 months
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MORDOR Malawi, Tanzania and Niger.
Please note: Each outcome will be analyzed separately for each study site.
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Each site will report outcomes at 24 months; Niger will also report outcomes at 48 months
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Fraction of isolates of pneumococcus exhibiting macrolide resistance by nasopharyngeal swabs in children 1-60 months
時間枠：Each site will report outcomes at 24 months; Niger will also report outcomes at 36 months
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MORDOR Malawi, Tanzania and Niger.
Please note: Each outcome will be analyzed separately for each study site.
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Each site will report outcomes at 24 months; Niger will also report outcomes at 36 months
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Prevalence of macrolide resistance in the stool as determined by genetic determinants or phenotypic testing
時間枠：Each site will report outcomes at 24 months; Niger will also report outcomes at 48 months
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MORDOR Malawi, Tanzania and Niger.
Please note: Each outcome will be analyzed separately for each study site.
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Each site will report outcomes at 24 months; Niger will also report outcomes at 48 months
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Fraction of conjunctival swabs yielding ocular chlamydia in children 1-60 months
時間枠：24 months
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MORDOR Malawi and Niger.
Please note: Each outcome will be analyzed separately for each study site.
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24 months
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Height over time in children aged 1-60 months
時間枠：Each site will report outcomes at 24 months; Niger will also report outcomes at 48 months
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MORDOR Malawi and Niger Please note: Each outcome will be analyzed separately in each of the two study sites.
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Each site will report outcomes at 24 months; Niger will also report outcomes at 48 months
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Weight for Height over time in children aged 1-60 months
時間枠：Each site will report outcomes at 24 months; Niger will also report outcomes at 48 months
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MORDOR Malawi and Niger Please note:Each outcome will be analyzed separately in each of the two study sites.
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Each site will report outcomes at 24 months; Niger will also report outcomes at 48 months
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
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Density of asexual stages and gametocytes, in children 1-60 months
時間枠：Each site will report outcomes at 24 months; Niger will also report outcomes at 48 months
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MORDOR Malawi and Niger Please note: Each outcome will be analyzed separately in each of the two study sites.
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Each site will report outcomes at 24 months; Niger will also report outcomes at 48 months
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Hemoglobin concentration and presence of anemia (hemoglobin <11 g/dL) in children 1-60 months
時間枠：Each site will report outcomes at 24 months; Niger will also report outcomes at 48 months
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MORDOR Malawi, Tanzania and Niger.
Please note: Each outcome will be analyzed separately for each study site.
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Each site will report outcomes at 24 months; Niger will also report outcomes at 48 months
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Genetic determinants of macrolide resistance in the nasopharynx (eg pneumococcal) in individuals 7-12 years of age
時間枠：24 months
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MORDOR Niger
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24 months
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Genetic determinants of macrolide resistance in the nasopharynx (eg pneumococcal) in individuals 1-60 month olds seen in local health clinics for a respiratory complaint
時間枠：24 months
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MORDOR Malawi, Tanzania and Niger.
Please note: Each outcome will be analyzed separately for each study site.
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24 months
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Rates of acute respiratory illness among children 1-60 months.
時間枠：6-24 months after baseline
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MORDOR Tanzania
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6-24 months after baseline
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Presence of the trachoma grades "follicular trachoma" (TF) and "intense inflammatory trachoma" (TI), as defined by the World Health Organization (WHO) simplified grading system, in children 1-60 months
時間枠：24 months
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MORDOR Malawi and Niger Please note: Each outcome will be analyzed separately for each study site.
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24 months
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Rates of diarrhea among children (1-60 months)
時間枠：6-24 months after baseline
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MORDOR Tanzania
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6-24 months after baseline
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Proportion of rectal/stool isolates with evidence of resistance (in for example E.coli) to macrolides and other antibiotics commonly used to treat pediatric infections among children 1-60 months
時間枠：6-24 months after baseline; Niger will also report outcomes at 48 months
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MORDOR Malawi, Tanzania and Niger.
Please note: Each outcome will be analyzed separately for each study site.
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6-24 months after baseline; Niger will also report outcomes at 48 months
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Proportions of E. coli isolates resistant to macrolides and to antibiotics commonly used to treat pediatric infections among children 1-60 months hospitalized for pneumonia and diarrhea.
時間枠：6-24 months after baseline
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MORDOR Tanzania
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6-24 months after baseline
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Studies of intestinal permeability and inflammation, microbial translocation, and immune activation assessed through venous sampling of children 6 months
時間枠：5 x over 24 weeks after baseline
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MORDOR Malawi
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5 x over 24 weeks after baseline
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Studies of intestinal permeability and inflammation, microbial translocation, and immune activation assessed through urine samples for L:M ratios of children 6 months
時間枠：5 x over 24 weeks after baseline
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MORDOR Malawi
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5 x over 24 weeks after baseline
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Studies of intestinal permeability and inflammation, microbial translocation, and immune activation assessed through stool (fecal neopterin) of children 6 months
時間枠：5 x over 24 weeks after baseline
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MORDOR Malawi
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5 x over 24 weeks after baseline
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Nasopharyngeal pneumococcal evidence of beta lactam and macrolide resistance in in children 1-60 months as measured by RNA-sequencing of the resistome
時間枠：Tanzania will report outcomes at 6-24 months. Each site will report outcomes at 24 months; Niger will also report outcomes at 36 months
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MORDOR Malawi, Tanzania and Niger.
Please note: Each outcome will be analyzed separately for each study site.
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Tanzania will report outcomes at 6-24 months. Each site will report outcomes at 24 months; Niger will also report outcomes at 36 months
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Nasopharyngeal pneumococcal macrolide resistance determinants (eg erythromycin ribosomal methylase B and mefA), serotype, and multilocus sequence type in children 1-60 months
時間枠：24 months
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MORDOR Niger
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24 months
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Microbiome in the stool, nasopharynx, nares, and conjunctiva in children aged 1-59 months, as measured using next generation sequencing. Arms will be compared using Euclidean distance and diversity compared using Simpson's index.
時間枠：24 months
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Investigators will examine the effects of mass azithromycin (pre-treatment and post-treatment) on the human microbiome of African children by performing metagenomic experiments. MORDOR Niger |
24 months
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Microbial diversity in the intestinal microbiomes of children aged 1-60 months as measured by using next generation sequencing
時間枠：24 months
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Investigators will examine the effects of mass azithromycin (pre-treatment and post-treatment) on the human microbiome of African children by performing metagenomic experiments. MORDOR Malawi |
24 months
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Serology for exposure to exotic pathogens of children aged 1-60 months as measured by lateral flow assays or Multiplex bead array
時間枠：24 months
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MORDOR Malawi
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24 months
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Head circumference over time in children aged 1-60 months
時間枠：24 months
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MORDOR Malawi
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24 months
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Knee-heel length over time in children aged 1-60 months
時間枠：24 months
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MORDOR Malawi
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24 months
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Resistance (in E.coli phenotypically or genetic determinants) in stool of children aged 1-60 months.
時間枠：Each site will report outcomes at 24 months; Niger will also report outcomes at 48 months
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MORDOR Malawi, Tanzania and Niger.
Please note: Each outcome will be analyzed separately for each study site.
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Each site will report outcomes at 24 months; Niger will also report outcomes at 48 months
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Prevalence of carriage of a panel of gastrointestinal parasites (Ancylostoma duodenale, Necator americanus, Ascaris lumbricoides, Trichuris trichiura, Giardia lamblia, Cryptosporidium hominis) of children aged 1-60 months
時間枠：Baseline
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MORDOR Malawi
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Baseline
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Prevalence of helicobacter pylori of children aged 1-60 months
時間枠：Baseline
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MORDOR Malawi
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Baseline
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Antibody response to enteric pathogens and malaria measured with a multiplex bead assay from dried blood spots collected from children 1 - 59 months
時間枠：Niger will report outcomes at 36, 48 and 60 months
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MORDOR Niger
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Niger will report outcomes at 36, 48 and 60 months
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協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
協力者
捜査官
- スタディディレクター：Elodie J Lebas, RN、University of California, San Francisco
出版物と役立つリンク
研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。
一般刊行物
- Porco TC, Stoller NE, Keenan JD, Bailey RL, Lietman TM. Public key cryptography for quality assurance in randomization for clinical trials. Contemp Clin Trials. 2015 May;42:167-8. doi: 10.1016/j.cct.2015.03.016. Epub 2015 Apr 7. No abstract available.
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研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始 (実際)
2014年11月1日
一次修了 (実際)
2020年8月27日
研究の完了 (実際)
2020年8月27日
試験登録日
最初に提出
2014年1月24日
QC基準を満たした最初の提出物
2014年1月24日
最初の投稿 (見積もり)
2014年1月29日
学習記録の更新
投稿された最後の更新 (実際)
2021年3月17日
QC基準を満たした最後の更新が送信されました
2021年3月15日
最終確認日
2021年3月1日
詳しくは
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。
Azithromycinの臨床試験
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University of Geneva, SwitzerlandUniversity of Lausanne募集