Randomised controlled trial testing the effect of cotrimoxazole prophylaxis on morbidity and mortality outcomes in breastfed HIV-exposed uninfected infants: study protocol
Identifieur interne : 003889 ( Ncbi/Merge ); précédent : 003888; suivant : 003890Randomised controlled trial testing the effect of cotrimoxazole prophylaxis on morbidity and mortality outcomes in breastfed HIV-exposed uninfected infants: study protocol
Auteurs : Anna Coutsoudis [Afrique du Sud] ; Brodie Daniels [Afrique du Sud] ; Eshia Moodley-Govender [Afrique du Sud] ; Noluthando Ngomane [Afrique du Sud] ; Linda Zako [Afrique du Sud] ; Elizabeth Spooner [Afrique du Sud] ; Photini Kiepiela [Afrique du Sud] ; Shabashini Reddy [Afrique du Sud] ; Louise Kuhn [États-Unis] ; Gita Ramjee [Afrique du Sud]Source :
- BMJ Open [ 2044-6055 ] ; 2016.
Abstract
No randomised controlled trial (RCT) has examined the efficacy of cotrimoxazole (CTX) prophylaxis in HIV-exposed uninfected (HEU) infants during the breastfeeding period, in this new era of effective prevention of mother-to-child transmission (PMTCT) prophylaxis. The efficacy of CTX prophylaxis has presently been demonstrated only in HIV-infected children. The absence of proven benefits in HEU breastfed infants associated with infectious diseases justifies an RCT as proposed. Herewith lies the rationale for conducting the proposed study.
A partially blinded RCT is proposed to evaluate the efficacy of CTX prophylaxis administered from 6 weeks of age to HEU infants receiving a PMTCT regimen. A non-inferiority design will be used, randomising 1298 infants to receive CTX or not to receive CTX. Participants will be reviewed at the following time points: 6 weeks (enrolment and randomisation), 10 weeks, 14 weeks, 4 months and monthly thereafter until 12 months of age. They will be evaluated for anthropometric growth, interval illness, CTX adherence, signs and symptoms of study drug toxicity, concomitant medication use, breastfeeding status and HIV infection status. The study will compare the incidence of grade 3 and grade 4 common childhood illnesses (focusing on pneumonia and diarrhoea) and all-cause mortality until 12 months of age. In a subset of participants, we will compare grade 3 and grade 4 haemoglobin and alanine aminotransferase results as well as investigate gut integrity.
The study has ethical approval from the University of KwaZulu-Natal Biomedical Research Ethics Committee (BFC212/13).
PACTR201311000621110 and DOH-27-0614-4728; Pre-results.
Url:
DOI: 10.1136/bmjopen-2015-010656
PubMed: 27406638
PubMed Central: 4947798
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Brodie" sort="Daniels, Brodie" uniqKey="Daniels B" first="Brodie" last="Daniels">Brodie Daniels</name><affiliation wicri:level="1"><nlm:aff id="af1"><addr-line>Department of Paediatrics and Child Health</addr-line>,<institution>University of KwaZulu-Natal</institution>,<addr-line>Durban</addr-line>,<country>South Africa</country></nlm:aff><country xml:lang="fr">Afrique du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Moodley Govender, Eshia" sort="Moodley Govender, Eshia" uniqKey="Moodley Govender E" first="Eshia" last="Moodley-Govender">Eshia Moodley-Govender</name><affiliation wicri:level="1"><nlm:aff id="af1"><addr-line>Department of Paediatrics and Child Health</addr-line>,<institution>University of KwaZulu-Natal</institution>,<addr-line>Durban</addr-line>,<country>South Africa</country></nlm:aff><country xml:lang="fr">Afrique du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Ngomane, Noluthando" sort="Ngomane, Noluthando" uniqKey="Ngomane N" first="Noluthando" last="Ngomane">Noluthando Ngomane</name><affiliation wicri:level="1"><nlm:aff id="af2"><addr-line>eThekwini Health Unit</addr-line>,<institution>eThekwini Municipality</institution>,<addr-line>Durban</addr-line>,<country>South Africa</country></nlm:aff><country xml:lang="fr">Afrique du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Zako, Linda" sort="Zako, Linda" uniqKey="Zako L" first="Linda" last="Zako">Linda Zako</name><affiliation wicri:level="1"><nlm:aff id="af2"><addr-line>eThekwini Health Unit</addr-line>,<institution>eThekwini Municipality</institution>,<addr-line>Durban</addr-line>,<country>South Africa</country></nlm:aff><country xml:lang="fr">Afrique du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Spooner, Elizabeth" sort="Spooner, Elizabeth" uniqKey="Spooner E" first="Elizabeth" last="Spooner">Elizabeth Spooner</name><affiliation wicri:level="1"><nlm:aff id="af1"><addr-line>Department of Paediatrics and Child Health</addr-line>,<institution>University of KwaZulu-Natal</institution>,<addr-line>Durban</addr-line>,<country>South Africa</country></nlm:aff><country xml:lang="fr">Afrique du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Kiepiela, Photini" sort="Kiepiela, Photini" uniqKey="Kiepiela P" first="Photini" last="Kiepiela">Photini Kiepiela</name><affiliation wicri:level="1"><nlm:aff id="af3"><addr-line>HIV Prevention Research Unit</addr-line>,<institution>Medical Research Council of South Africa</institution>,<addr-line>Durban</addr-line>,<country>South Africa</country></nlm:aff><country xml:lang="fr">Afrique du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Reddy, Shabashini" sort="Reddy, Shabashini" uniqKey="Reddy S" first="Shabashini" last="Reddy">Shabashini Reddy</name><affiliation wicri:level="1"><nlm:aff id="af3"><addr-line>HIV Prevention Research Unit</addr-line>,<institution>Medical Research Council of South Africa</institution>,<addr-line>Durban</addr-line>,<country>South Africa</country></nlm:aff><country xml:lang="fr">Afrique du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Kuhn, Louise" sort="Kuhn, Louise" uniqKey="Kuhn L" first="Louise" last="Kuhn">Louise Kuhn</name><affiliation wicri:level="1"><nlm:aff id="af4"><addr-line>Department of Epidemiology</addr-line>,<institution>Mailman School of Public Health, Columbia University</institution>,<addr-line>New York, New York</addr-line>,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Ramjee, Gita" sort="Ramjee, Gita" uniqKey="Ramjee G" first="Gita" last="Ramjee">Gita Ramjee</name><affiliation wicri:level="1"><nlm:aff id="af3"><addr-line>HIV Prevention Research Unit</addr-line>,<institution>Medical Research Council of South Africa</institution>,<addr-line>Durban</addr-line>,<country>South Africa</country></nlm:aff><country xml:lang="fr">Afrique du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">BMJ Open</title><idno type="eISSN">2044-6055</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Introduction</title><p>No randomised controlled trial (RCT) has examined the efficacy of cotrimoxazole (CTX) prophylaxis in HIV-exposed uninfected (HEU) infants during the breastfeeding period, in this new era of effective prevention of mother-to-child transmission (PMTCT) prophylaxis. The efficacy of CTX prophylaxis has presently been demonstrated only in HIV-infected children. The absence of proven benefits in HEU breastfed infants associated with infectious diseases justifies an RCT as proposed. Herewith lies the rationale for conducting the proposed study.</p></sec><sec><title>Methods</title><p>A partially blinded RCT is proposed to evaluate the efficacy of CTX prophylaxis administered from 6 weeks of age to HEU infants receiving a PMTCT regimen. A non-inferiority design will be used, randomising 1298 infants to receive CTX or not to receive CTX. Participants will be reviewed at the following time points: 6 weeks (enrolment and randomisation), 10 weeks, 14 weeks, 4 months and monthly thereafter until 12 months of age. They will be evaluated for anthropometric growth, interval illness, CTX adherence, signs and symptoms of study drug toxicity, concomitant medication use, breastfeeding status and HIV infection status. The study will compare the incidence of grade 3 and grade 4 common childhood illnesses (focusing on pneumonia and diarrhoea) and all-cause mortality until 12 months of age. In a subset of participants, we will compare grade 3 and grade 4 haemoglobin and alanine aminotransferase results as well as investigate gut integrity.</p></sec><sec><title>Ethics and dissemination</title><p>The study has ethical approval from the University of KwaZulu-Natal Biomedical Research Ethics Committee (BFC212/13).</p></sec><sec><title>Trial registration numbers</title><p>PACTR201311000621110 and DOH-27-0614-4728; Pre-results.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Chintu, C" uniqKey="Chintu C">C Chintu</name></author><author><name sortKey="Bhat, Gj" uniqKey="Bhat G">GJ Bhat</name></author><author><name sortKey="Walker, As" uniqKey="Walker A">AS Walker</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Coutsoudis, A" uniqKey="Coutsoudis A">A Coutsoudis</name></author><author><name sortKey="Coovadia, Hm" uniqKey="Coovadia H">HM Coovadia</name></author><author><name 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<front><journal-meta><journal-id journal-id-type="nlm-ta">BMJ Open</journal-id><journal-id journal-id-type="iso-abbrev">BMJ Open</journal-id><journal-id journal-id-type="hwp">bmjopen</journal-id><journal-id journal-id-type="publisher-id">bmjopen</journal-id><journal-title-group><journal-title>BMJ Open</journal-title></journal-title-group><issn pub-type="epub">2044-6055</issn><publisher><publisher-name>BMJ Publishing Group</publisher-name><publisher-loc>BMA House, Tavistock Square, London, WC1H 9JR</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">27406638</article-id><article-id pub-id-type="pmc">4947798</article-id><article-id pub-id-type="publisher-id">bmjopen-2015-010656</article-id><article-id pub-id-type="doi">10.1136/bmjopen-2015-010656</article-id><article-categories><subj-group subj-group-type="heading"><subject>Public Health</subject><subj-group><subject>Protocol</subject></subj-group></subj-group><subj-group subj-group-type="hwp-journal-coll"><subject>1506</subject><subject>1724</subject><subject>1719</subject><subject>1842</subject></subj-group></article-categories><title-group><article-title>Randomised controlled trial testing the effect of cotrimoxazole prophylaxis on morbidity and mortality outcomes in breastfed HIV-exposed uninfected infants: study protocol</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Coutsoudis</surname><given-names>Anna</given-names></name><xref ref-type="aff" rid="af1">1</xref></contrib><contrib contrib-type="author"><name><surname>Daniels</surname><given-names>Brodie</given-names></name><xref ref-type="aff" rid="af1">1</xref></contrib><contrib contrib-type="author"><name><surname>Moodley-Govender</surname><given-names>Eshia</given-names></name><xref ref-type="aff" rid="af1">1</xref></contrib><contrib contrib-type="author"><name><surname>Ngomane</surname><given-names>Noluthando</given-names></name><xref ref-type="aff" rid="af2">2</xref></contrib><contrib contrib-type="author"><name><surname>Zako</surname><given-names>Linda</given-names></name><xref ref-type="aff" rid="af2">2</xref></contrib><contrib contrib-type="author"><name><surname>Spooner</surname><given-names>Elizabeth</given-names></name><xref ref-type="aff" rid="af1">1</xref></contrib><contrib contrib-type="author"><name><surname>Kiepiela</surname><given-names>Photini</given-names></name><xref ref-type="aff" rid="af3">3</xref></contrib><contrib contrib-type="author"><name><surname>Reddy</surname><given-names>Shabashini</given-names></name><xref ref-type="aff" rid="af3">3</xref></contrib><contrib contrib-type="author"><name><surname>Kuhn</surname><given-names>Louise</given-names></name><xref ref-type="aff" rid="af4">4</xref></contrib><contrib contrib-type="author"><name><surname>Ramjee</surname><given-names>Gita</given-names></name><xref ref-type="aff" rid="af3">3</xref></contrib></contrib-group><aff id="af1"><label>1</label><addr-line>Department of Paediatrics and Child Health</addr-line>,<institution>University of KwaZulu-Natal</institution>,<addr-line>Durban</addr-line>,<country>South Africa</country></aff><aff id="af2"><label>2</label><addr-line>eThekwini Health Unit</addr-line>,<institution>eThekwini Municipality</institution>,<addr-line>Durban</addr-line>,<country>South Africa</country></aff><aff id="af3"><label>3</label><addr-line>HIV Prevention Research Unit</addr-line>,<institution>Medical Research Council of South Africa</institution>,<addr-line>Durban</addr-line>,<country>South Africa</country></aff><aff id="af4"><label>4</label><addr-line>Department of Epidemiology</addr-line>,<institution>Mailman School of Public Health, Columbia University</institution>,<addr-line>New York, New York</addr-line>,<country>USA</country></aff><author-notes><corresp><label>Correspondence to</label> Dr Brodie Daniels; <email>Daniels@ukzn.ac.za</email></corresp></author-notes><pub-date pub-type="collection"><year>2016</year></pub-date><pub-date pub-type="epub"><day>12</day><month>7</month><year>2016</year></pub-date><volume>6</volume><issue>7</issue><elocation-id>e010656</elocation-id><history><date date-type="received"><day>24</day><month>11</month><year>2015</year></date><date date-type="rev-recd"><day>17</day><month>5</month><year>2016</year></date><date date-type="accepted"><day>17</day><month>5</month><year>2016</year></date></history><permissions><copyright-statement>Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/</copyright-statement><copyright-year>2016</copyright-year><license license-type="open-access"><license-p>This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by-nc/4.0/">http://creativecommons.org/licenses/by-nc/4.0/</ext-link></license-p></license></permissions><self-uri xlink:title="pdf" xlink:href="bmjopen-2015-010656.pdf"></self-uri><abstract><sec><title>Introduction</title><p>No randomised controlled trial (RCT) has examined the efficacy of cotrimoxazole (CTX) prophylaxis in HIV-exposed uninfected (HEU) infants during the breastfeeding period, in this new era of effective prevention of mother-to-child transmission (PMTCT) prophylaxis. The efficacy of CTX prophylaxis has presently been demonstrated only in HIV-infected children. The absence of proven benefits in HEU breastfed infants associated with infectious diseases justifies an RCT as proposed. Herewith lies the rationale for conducting the proposed study.</p></sec><sec><title>Methods</title><p>A partially blinded RCT is proposed to evaluate the efficacy of CTX prophylaxis administered from 6 weeks of age to HEU infants receiving a PMTCT regimen. A non-inferiority design will be used, randomising 1298 infants to receive CTX or not to receive CTX. Participants will be reviewed at the following time points: 6 weeks (enrolment and randomisation), 10 weeks, 14 weeks, 4 months and monthly thereafter until 12 months of age. They will be evaluated for anthropometric growth, interval illness, CTX adherence, signs and symptoms of study drug toxicity, concomitant medication use, breastfeeding status and HIV infection status. The study will compare the incidence of grade 3 and grade 4 common childhood illnesses (focusing on pneumonia and diarrhoea) and all-cause mortality until 12 months of age. In a subset of participants, we will compare grade 3 and grade 4 haemoglobin and alanine aminotransferase results as well as investigate gut integrity.</p></sec><sec><title>Ethics and dissemination</title><p>The study has ethical approval from the University of KwaZulu-Natal Biomedical Research Ethics Committee (BFC212/13).</p></sec><sec><title>Trial registration numbers</title><p>PACTR201311000621110 and DOH-27-0614-4728; Pre-results.</p></sec></abstract><kwd-group><kwd>HIV-exposed uninfected infants</kwd><kwd>exclusive breastfeeding</kwd><kwd>cotrimoxazole prophylaxis</kwd></kwd-group></article-meta></front></pmc><affiliations><list><country><li>Afrique du Sud</li><li>États-Unis</li></country></list><tree><country name="Afrique du Sud"><noRegion><name sortKey="Coutsoudis, Anna" sort="Coutsoudis, Anna" uniqKey="Coutsoudis A" first="Anna" last="Coutsoudis">Anna Coutsoudis</name></noRegion><name sortKey="Daniels, Brodie" sort="Daniels, Brodie" uniqKey="Daniels B" first="Brodie" last="Daniels">Brodie Daniels</name><name sortKey="Kiepiela, Photini" sort="Kiepiela, Photini" uniqKey="Kiepiela P" first="Photini" last="Kiepiela">Photini Kiepiela</name><name sortKey="Moodley Govender, Eshia" sort="Moodley Govender, Eshia" uniqKey="Moodley Govender E" first="Eshia" last="Moodley-Govender">Eshia Moodley-Govender</name><name sortKey="Ngomane, Noluthando" sort="Ngomane, Noluthando" uniqKey="Ngomane N" first="Noluthando" last="Ngomane">Noluthando Ngomane</name><name sortKey="Ramjee, Gita" sort="Ramjee, Gita" uniqKey="Ramjee G" first="Gita" last="Ramjee">Gita Ramjee</name><name sortKey="Reddy, Shabashini" sort="Reddy, Shabashini" uniqKey="Reddy S" first="Shabashini" last="Reddy">Shabashini Reddy</name><name sortKey="Spooner, Elizabeth" sort="Spooner, Elizabeth" uniqKey="Spooner E" first="Elizabeth" last="Spooner">Elizabeth Spooner</name><name sortKey="Zako, Linda" sort="Zako, Linda" uniqKey="Zako L" first="Linda" last="Zako">Linda Zako</name></country><country name="États-Unis"><noRegion><name sortKey="Kuhn, Louise" sort="Kuhn, Louise" uniqKey="Kuhn L" first="Louise" last="Kuhn">Louise Kuhn</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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